WorldWideScience

Sample records for striatum globus pallidus

  1. Neurokinin-1 receptor activation in globus pallidus

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2009-10-01

    Full Text Available The undecapeptide substance P has been demonstrated to modulate neuronal activity in a number of brain regions by acting on neurokinin-1 receptors. Anatomical studies revealed a moderate level of neurokinin-1 receptor in rat globus pallidus. To determine the electrophysiological effects of neurokinin-1 receptor activation in globus pallidus, whole-cell patch-clamp recordings were performed in the present study. Under current-clamp recordings, neurokinin-1 receptor agonist, [Sar9, Met(O211] substance P (SM-SP at 1 μM, depolarized globus pallidus neurons and increased their firing rate. Consistently, SM-SP induced an inward current under voltage-clamp recording. The depolarization evoked by SM-SP persisted in the presence of tetrodotoxin, glutamate and GABA receptor antagonists, indicating its direct postsynaptic effects. The neurokinin-1 receptor antagonist, SR140333B, could block SM-SP-induced depolarization. Further experiments showed that suppression of potassium conductance was the predominant ionic mechanism of SM-SP-induced depolarization. To determine if neurokinin-1 receptor activation exerts any effects on GABAergic and glutamatergic neurotransmission, the action of SM-SP on synaptic currents was studied. SM-SP significantly increased the frequency of spontaneous inhibitory postsynaptic currents, but only induced a transient increase in the frequency of miniature inhibitory postsynaptic currents. No change was observed in both spontaneous and miniature excitatory postsynaptic currents. Based on the direct excitatory effects of SM-SP on pallidal neurons, we hypothesize that neurokinin-1 receptor activation in globus pallidus may be involved in the beneficial effect of substance P in Parkinson’s disease.

  2. Changes in globus pallidus with (pre)term kernicterus

    NARCIS (Netherlands)

    P. Govaert (Paul); R.M.C. Swarte (Renate); S.G.F. Robben (Simon); I.F.M. de Coo (René); N. Weisglas-Kuperus (Nynke); M. Sinaasappel (Maarten); J. Barkovich (James); Y.B. de Rijke (Yolanda); M.H. Lequin (Maarten)

    2003-01-01

    textabstractOBJECTIVE: We report serial magnetic resonance (MR) and sonographic behavior of globus pallidus in 5 preterm and 3 term infants with kernicterus and describe the clinical context in very low birth weight preterm infants. On the basis of this information, we suggest

  3. Differential contributions of the globus pallidus and ventral thalamus to stimulus-response learning in humans.

    Science.gov (United States)

    Schroll, Henning; Horn, Andreas; Gröschel, Christine; Brücke, Christof; Lütjens, Götz; Schneider, Gerd-Helge; Krauss, Joachim K; Kühn, Andrea A; Hamker, Fred H

    2015-11-15

    The ability to learn associations between stimuli, responses and rewards is a prerequisite for survival. Models of reinforcement learning suggest that the striatum, a basal ganglia input nucleus, vitally contributes to these learning processes. Our recently presented computational model predicts, first, that not only the striatum, but also the globus pallidus contributes to the learning (i.e., exploration) of stimulus-response associations based on rewards. Secondly, it predicts that the stable execution (i.e., exploitation) of well-learned associations involves further learning in the thalamus. To test these predictions, we postoperatively recorded local field potentials (LFPs) from patients that had undergone surgery for deep brain stimulation to treat severe movement disorders. Macroelectrodes were placed either in the globus pallidus or in the ventral thalamus. During recordings, patients performed a reward-based stimulus-response learning task that comprised periods of exploration and exploitation. We analyzed correlations between patients' LFP amplitudes and model-based estimates of their reward expectations and reward prediction errors. In line with our first prediction, pallidal LFP amplitudes during the presentation of rewards and reward omissions correlated with patients' reward prediction errors, suggesting pallidal access to reward-based teaching signals. Unexpectedly, the same was true for the thalamus. In further support of this prediction, pallidal LFP amplitudes during stimulus presentation correlated with patients' reward expectations during phases of low reward certainty - suggesting pallidal participation in the learning of stimulus-response associations. In line with our second prediction, correlations between thalamic stimulus-related LFP amplitudes and patients' reward expectations were significant within phases of already high reward certainty, suggesting thalamic participation in exploitation. Copyright © 2015 Elsevier Inc. All rights

  4. Alexithymia Associated With Bilateral Globus Pallidus Lesions After Carbon Monoxide Poisoning

    OpenAIRE

    Mei-Feng Huang; Yi-Chun Yeh; Hin-Yeung Tsang; Cheng-Sheng Chen

    2010-01-01

    Alexithymia refers to a person's inability to identify and describe feelings. We present a patient who developed alexithymia after carbon monoxide poisoning following a suicide attempt by burning charcoal in an enclosed space. Brain computed tomography revealed bilateral globus pallidus hypoxic lesions. Because of the time frame and the presence of brain structural lesions, the alexithymia in this patient was thought to be caused by bilateral globus pallidus hypoxic lesions resulting from car...

  5. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  6. Dementia mimicking a sudden cognitive and behavioral change induced by left globus pallidus infarction: review of two cases.

    Science.gov (United States)

    Kim, Su Hyun; Park, Kee Hyung; Sung, Young Hee; Lee, Yeoung Bae; Park, Hyun Mi; Shin, Dong Jin

    2008-09-15

    Recently there has been increasing interest in the non-motor functions of the globus pallidus, and especially its role in cognitive processing. We experienced two patients with acute cognitive and behavior changes after globus pallidus infarctions. Examination of both revealed inattention, decreased verbal fluency, emotional blunting, and amnesia. There were no other sensory or motor symptoms. Brain magnetic resonance imaging (MRI) showed focal acute cerebral infarction in the left globus pallidus. Neuropsychological assessment revealed decreased frontal executive function, with verbal memory disturbance. These cases suggest that strategic infarction dementia can result from a single globus pallidus lesion.

  7. Are Subthalamicus Nucleus, Internal, Globus Pallidus and Thalamus Involved in Thinking?

    Czech Academy of Sciences Publication Activity Database

    Minks, E.; Jurák, Pavel; Chládek, Jan; Hummelová, Z.

    2015-01-01

    Roč. 86, e4 (2015), s. 46 ISSN 0022-3050. [Annual Meeting of the Association-of-British-Neurologists (ABN). 10.09.2015, London] Institutional support: RVO:68081731 Keywords : Subthalamicus Nucleus * Globus Pallidus * Involving Thinking Subject RIV: BH - Optics, Masers, Lasers

  8. Kernicterus with abnormal high-signal changes bilaterally in the globus pallidus: A case report.

    LENUS (Irish Health Repository)

    Culleton, S

    2018-04-01

    Kernicterus is a relatively rare consequence of hyperbilirubinemia. There is an important role for MRI imaging for this entity in the appropriate clinical context as there are distinct signal changes in the globus pallidus. A case report and image findings are presented

  9. Orexin-A increases the activity of globus pallidus neurons in both normal and parkinsonian rats.

    Science.gov (United States)

    Xue, Yan; Yang, Yu-Ting; Liu, Hong-Yun; Chen, Wen-Fang; Chen, An-Qi; Sheng, Qing; Chen, Xin-Yi; Wang, Ying; Chen, Hua; Liu, Hong-Xia; Pang, Ya-Yan; Chen, Lei

    2016-09-01

    Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Hyperintense globus pallidus on T1-weighted MR imaging in acute kernicterus: is it common or rare?

    Energy Technology Data Exchange (ETDEWEB)

    Coskun, Abdulhakim; Yikilmaz, Ali; Karahan, Okkes Ibrahim; Manav, Ali [Erciyes University Medical School, Department of Radiology, Kayseri (Turkey); Kumandas, Sefer [Erciyes University Medical School, Department of Neuropediatry, Kayseri (Turkey); Akcakus, Mustafa [Erciyes University Medical School, Department of Neonatalogy, Kayseri (Turkey)

    2005-06-01

    Globus pallidus involvement is a well-known magnetic resonance (MR) imaging finding of acute kernicterus. However, it is not clear how early the involvement of globus pallidus occurs and whether or not it is seen in every case. Therefore, we aimed to investigate the globus pallidus involvement in 13 neonates with acute kernicterus by MR imaging. Thirteen neonates who were admitted with jaundice, encephalopathy and indirect hyperbilirubinemia (mean, 37.0 mg/dl) were prospectively evaluated with cranial MR imaging. Pathological signal changes were noted concerning the globus pallidus. Eight of the 13 patients demonstrated bilateral, symmetric increased signal intensity in the globus pallidus on T1-weighted MR imaging. These lesions were not apparent on T2-weighted images. Multiple parenchymal punctuate T1 hyperintense lesions were detected in one patient without globus pallidus involvement. This appearance was consistent with hemorrhage. The MR imaging findings of the other four patients showed no evidence of abnormality. The symmetric involvement of globus pallidus seen as hyperintense on T1-weighted MR imaging is a common and characteristic finding of acute kernicterus. (orig.)

  11. Hyperintense globus pallidus on T1-weighted MR imaging in acute kernicterus: is it common or rare?

    International Nuclear Information System (INIS)

    Coskun, Abdulhakim; Yikilmaz, Ali; Karahan, Okkes Ibrahim; Manav, Ali; Kumandas, Sefer; Akcakus, Mustafa

    2005-01-01

    Globus pallidus involvement is a well-known magnetic resonance (MR) imaging finding of acute kernicterus. However, it is not clear how early the involvement of globus pallidus occurs and whether or not it is seen in every case. Therefore, we aimed to investigate the globus pallidus involvement in 13 neonates with acute kernicterus by MR imaging. Thirteen neonates who were admitted with jaundice, encephalopathy and indirect hyperbilirubinemia (mean, 37.0 mg/dl) were prospectively evaluated with cranial MR imaging. Pathological signal changes were noted concerning the globus pallidus. Eight of the 13 patients demonstrated bilateral, symmetric increased signal intensity in the globus pallidus on T1-weighted MR imaging. These lesions were not apparent on T2-weighted images. Multiple parenchymal punctuate T1 hyperintense lesions were detected in one patient without globus pallidus involvement. This appearance was consistent with hemorrhage. The MR imaging findings of the other four patients showed no evidence of abnormality. The symmetric involvement of globus pallidus seen as hyperintense on T1-weighted MR imaging is a common and characteristic finding of acute kernicterus. (orig.)

  12. Emotional and motivational changes after bilateral lesions of the globus pallidus.

    Science.gov (United States)

    Vijayaraghavan, Lavanya; Vaidya, Jatin G; Humphreys, Clare T; Beglinger, Leigh J; Paradiso, Sergio

    2008-05-01

    This study investigated motivational changes in a 44 year-old man (PJ) who developed considerable reduction in spontaneous activity and speech, flat affect, social withdrawal, loss of interest, inability to "feel," and lack of concern regarding his medical condition after bilateral, focal, anoxic lesions of the globus pallidus. PJ and 30 male controls performed a task designed to parse hedonic evaluation, or liking, from incentive motivation, or wanting. Affective stimuli were presented on a computer screen and subjects controlled viewing time by pressing keys. PJ's liking and wanting of unpleasant stimuli was similar to that of controls. In response to pleasant stimuli, PJ showed normal ratings of wanting and hedonic appreciation, but significantly reduced viewing time or made no responses. Active withdrawal from liked stimuli could constitute the basic mechanism underlying poor motivation and social withdrawal associated with globus pallidus damage.

  13. Neurobehavioural Changes in a Patient with Bilateral Lesions of the Globus Pallidus

    Directory of Open Access Journals (Sweden)

    R. Haaxma

    1993-01-01

    Full Text Available This study has characterized the long-term neurobehavioural changes in a woman who, following the intake of an unidentified substance, sustained subtotal bilateral lesions of the globus pallidus and small lesions at selective sites adjacent to it. Associated with these lesions was a significantly reduced blood flow in multiple frontal cortical regions, most prominently in area 10, the anterior cingulate and the supplementary motor cortex. Her cognitive deficits were generally consistent with those found in patients with frontal lobe dysfunction but some deficits, i.e. in visual memory and learning, were more compatible with temporal lobe dysfunction. Incapacitating personality or obsessive compulsive changes as reported by others with similar lesions were absent and she could live independently. The cognitive changes are consistent with the view that the globus pallidus has important functions in mediating how internal representations of stimulus input are converted into various forms of action, for example, in planning solutions to problems and in working memory.

  14. Simulating the Effects of Short-Term Synaptic Plasticity on Postsynaptic Dynamics in the Globus Pallidus

    Directory of Open Access Journals (Sweden)

    Moran eBrody

    2013-08-01

    Full Text Available The rat globus pallidus (GP is one of the nuclei of the basal ganglia and plays an important role in a variety of motor and cognitive processes. In vivo studies have shown that repetitive stimulation evokes complex modulations of GP activity. In vitro and computational studies have suggested that short-term synaptic plasticity (STP could be one of the underlying mechanisms. The current study used simplified single compartment modeling to explore the possible effect of STP on the activity of GP neurons during low and high frequency stimulation. To do this we constructed a model of a GP neuron connected to a small network of neurons from the three major input sources to GP neurons: striatum (Str, subthalamic nucleus (STN and GP collaterals. All synapses were implemented with a kinetic model of STP. The in vitro recordings of responses to low frequency repetitive stimulation were highly reconstructed, including rate changes and locking to the stimulus. Mainly involved were fast forms of plasticity which have been found at these synapses. . The simulations were qualitatively compared to a data set previously recorded in vitro in our lab. Reconstructions of experimental responses to high frequency stimulation required adding slower forms of plasticity to the STN and GP collateral synapses, as well as adding metabotropic receptors to the STN-GP synapses. These finding suggest the existence of as yet unreported slower short-term dynamics in the GP. The computational model made additional predictions about GP activity during low and high frequency stimulation that may further our understanding of the mechanisms underlying repetative stimulation of the GP.

  15. Globus Pallidus Interna Deep Brain Stimulation in a Patient with Medically Intractable Meige Syndrome

    Directory of Open Access Journals (Sweden)

    Dae-Woong Bae

    2014-10-01

    Full Text Available Medical therapies in patients with Meige syndrome, including botulinum toxin injection, have been limited because of incomplete response or adverse side effects. We evaluated a patient with Meige syndrome who was successfully treated with deep brain stimulation (DBS in the globus pallidus interna (GPi. This case report and other previous reports suggest that bilateral GPi DBS may be an effective treatment for medically refractory Meige syndrome, without significant adverse effects.

  16. Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation.

    Science.gov (United States)

    Shaikh, Aasef G; Mewes, Klaus; DeLong, Mahlon R; Gross, Robert E; Triche, Shirley D; Jinnah, H A; Boulis, Nicholas; Willie, Jon T; Freeman, Alan; Alexander, Garrett E; Aia, Pratibha; Butefisch, Cathrine M; Esper, Christine D; Factor, Stewart A

    2015-02-01

    Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown. We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled. Consistent with previous studies, deep brain stimulation improved the overall the Burke-Fahn-Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months. Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats

    Directory of Open Access Journals (Sweden)

    Hui-Ling Diao

    2017-11-01

    Full Text Available The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.

  18. Aberrant resting-state corticostriatal functional connectivity in cirrhotic patients with hyperintense globus pallidus on T1-weighted MR imaging.

    Directory of Open Access Journals (Sweden)

    Xi-Qi Zhu

    Full Text Available Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting

  19. Deep Brain Stimulation of the internal globus pallidus in refractory Tourette Syndrome.

    Science.gov (United States)

    Smeets, A Y J M; Duits, A A; Plantinga, B R; Leentjens, A F G; Oosterloo, M; Visser-Vandewalle, V; Temel, Y; Ackermans, L

    2016-03-01

    Deep Brain Stimulation in psychiatric disorders is becoming an increasingly performed surgery. At present, seven different targets have been stimulated in Tourette Syndrome, including the internal globus pallidus. We describe the effects on tics and comorbid behavioral disorders of Deep Brain Stimulation of the anterior internal globus pallidus in five patients with refractory Tourette Syndrome. This study was performed as an open label study with follow-up assessment between 12 and 38 months. Patients were evaluated twice, one month before surgery and at long-term follow-up. Primary outcome was tic severity, assessed by several scales. Secondary outcomes were comorbid behavioral disorders, mood and cognition. The final position of the active contacts of the implanted electrodes was investigated and side effects were reported. Three males and two females were included with a mean age of 41.6 years (SD 9.7). The total post-operative score on the Yale Global Tic Severity Scale was significantly lower than the pre-operative score (42.2±4.8 versus 12.8±3.8, P=0.043). There was also a significant reduction on the modified Rush Video-Based Tic Rating Scale (13.0±2.0 versus 7.0±1.6, P=0.041) and in the total number of video-rated tics (259.6±107.3 versus 49.6±24.8, P=0.043). No significant difference on the secondary outcomes was found, however, there was an improvement on an individual level for obsessive-compulsive behavior. The final position of the active contacts was variable in our sample and no relationship between position and stimulation effects could be established. Our study suggests that Deep Brain Stimulation of the anterior internal globus pallidus is effective in reducing tic severity, and possibly also obsessive-compulsive behavior, in refractory Tourette patients without serious adverse events or side-effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

    Science.gov (United States)

    Mastro, Kevin J.; Bouchard, Rachel S.; Holt, Hiromi A. K.

    2014-01-01

    Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)–Cre and parvalbumin (PV)–Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6–GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV–GPe neurons. In contrast, PV–GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6–GPe and PV–GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease. PMID:24501350

  1. Left globus pallidus abnormality in never-medicated patients with schizophrenia

    International Nuclear Information System (INIS)

    Early, T.S.; Reiman, E.M.; Raichle, M.E.; Spitznagel, E.L.

    1987-01-01

    Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5 patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found

  2. Globus pallidus high-signal lesions: A predominant MRI finding in children with neurofibromatosis type 1

    Directory of Open Access Journals (Sweden)

    Arif Khan

    2013-01-01

    Full Text Available Introduction: Lesions of the brain, recognized as unidentified bright objects (UBOs, are commonly observed as areas of increased T2-weighted signal intensity on magnetic resonance imaging (MRI in children with neurofibromatosis type 1 (NF1. Identification of these lesions is not currently encompassed in the National Institute of Health (NIH diagnostic criteria for NF1. Objective: We aimed to determine the prevalence of UBOs in children with NF1 and identify areas of the brain that are commonly affected by these lesions, allowing us to evaluate whether UBOs should be included in the diagnostic criteria for the diagnosis of NF1. Materials and Methods: We reviewed the cranial MRI scans of 22 children who had been diagnosed with sporadic or familial NF1 in accordance with the criteria established by NIH. UBOs were present in 81% of the children with NF1. Results: These lesions have a predilection for specific areas of the brain, including the globus pallidus (72%, cerebellum (66%, brainstem (27% and cerebral hemispheres (16%. The prevalence of UBOs identified varied significantly with age and sex; they were infrequent in children less than 4 years of age but were common in those aged between 4 and 12 years of age. UBOs were more commonly seen in males (66.6% compared with females (33.3%. Repeat MRI scan on a subset of these patients with UBOs did not show any significant changes despite a worsening in clinical symptoms. Conclusion and Discussion: We have shown that UBOs are a common finding in children with NF1, and are most prevalent between the ages of 4 and 12 years. Many sites of the brain are affected by these lesions, most notably the globus pallidus and the cerebellum. Further research must be conducted to elucidate the significance of UBOs in patients with NF1 and whether these lesions have any utility in the clinical detection of NF1.

  3. New MRI findings in Creutzfeldt-Jakob disease: high signal in the globus pallidus on T 1-weighted images

    International Nuclear Information System (INIS)

    Priester, J.A. de; Wilmink, J.T.; Jansen, G.H.; Kruijk, J.R. de

    1999-01-01

    We report a 49-year-old woman with Creutzfeldt-Jakob disease (CJD). In addition to typical high-signal lesions on proton-density and T 2-weighted images there was high signal in the globus pallidus bilaterally on T 1-weighted images. The latter feature has not been described previously and probably due to deposition of prion protein, as found at autopsy. (orig.)

  4. New MRI findings in Creutzfeldt-Jakob disease: high signal in the globus pallidus on T 1-weighted images

    Energy Technology Data Exchange (ETDEWEB)

    Priester, J.A. de; Wilmink, J.T. [Dept. of Radiology, University Hospital Maastricht (Netherlands); Jansen, G.H. [Department of Neuropathology, University Hospital Utrecht (Netherlands); Kruijk, J.R. de [Department of Neurology, University Hospital Maastricht (Netherlands)

    1999-04-01

    We report a 49-year-old woman with Creutzfeldt-Jakob disease (CJD). In addition to typical high-signal lesions on proton-density and T 2-weighted images there was high signal in the globus pallidus bilaterally on T 1-weighted images. The latter feature has not been described previously and probably due to deposition of prion protein, as found at autopsy. (orig.) With 3 figs., 11 refs.

  5. Globus pallidus MR signal abnormalities in children with chronic liver disease and/or porto-systemic shunting

    Energy Technology Data Exchange (ETDEWEB)

    Hanquinet, Sylviane; Anooshiravani, Mehrak; Merlini, Laura [University Hospital of Geneva, Department of Pediatric Radiology, Geneva (Switzerland); Morice, Claire; Cousin, Vladimir; McLin, Valerie A. [University Hospital of Geneva, Swiss Center for Liver Disease in Children, Geneva (Switzerland); Courvoisier, Delphine S. [University Hospital of Geneva, Division of Quality of Care, Geneva (Switzerland)

    2017-10-15

    Detection of subclinical hepatic encephalopathy in children is difficult. We aimed to assess the changes in imaging of the central nervous system in children with chronic liver disease using MR imaging, diffusion, and {sup 1}H -spectroscopy. Forty three children with chronic liver disease and/or porto-systemic shunting (111.4±56.9 months) and 24 controls (72.0±51.8 months) underwent brain MRI/spectroscopy on a 1.5T to examine T1, T2, ADC, Cho/Cr, ml/Cr, Glx/Cr ratio spectroscopy in the globus pallidus. Patients were divided into 3 groups according to the ratios of globus pallidus/putamen T1 signal: isointense (i), hyperintense (h), much more hyperintense (h+). The relationship with clinical and biological data was analyzed. T1 signal intensity and ml/Cr were significantly different between controls and group h+ (p=0.001). ADC did not differ significantly between groups. Age correlated strongly with the presence of a T1 signal ratio (p > 0.001). There was no correlation between imaging findings and biological parameters. In children with chronic liver disease and/or porto-systemic shunting, the presence of a hyperintense T1 signal in the globus pallidus correlated strongly with age. Biological and clinical parameters were not predictive of these changes. MRI may become a useful screening tool for hepatic encephalopathy in children. (orig.)

  6. Globus pallidus MR signal abnormalities in children with chronic liver disease and/or porto-systemic shunting

    International Nuclear Information System (INIS)

    Hanquinet, Sylviane; Anooshiravani, Mehrak; Merlini, Laura; Morice, Claire; Cousin, Vladimir; McLin, Valerie A.; Courvoisier, Delphine S.

    2017-01-01

    Detection of subclinical hepatic encephalopathy in children is difficult. We aimed to assess the changes in imaging of the central nervous system in children with chronic liver disease using MR imaging, diffusion, and 1 H -spectroscopy. Forty three children with chronic liver disease and/or porto-systemic shunting (111.4±56.9 months) and 24 controls (72.0±51.8 months) underwent brain MRI/spectroscopy on a 1.5T to examine T1, T2, ADC, Cho/Cr, ml/Cr, Glx/Cr ratio spectroscopy in the globus pallidus. Patients were divided into 3 groups according to the ratios of globus pallidus/putamen T1 signal: isointense (i), hyperintense (h), much more hyperintense (h+). The relationship with clinical and biological data was analyzed. T1 signal intensity and ml/Cr were significantly different between controls and group h+ (p=0.001). ADC did not differ significantly between groups. Age correlated strongly with the presence of a T1 signal ratio (p > 0.001). There was no correlation between imaging findings and biological parameters. In children with chronic liver disease and/or porto-systemic shunting, the presence of a hyperintense T1 signal in the globus pallidus correlated strongly with age. Biological and clinical parameters were not predictive of these changes. MRI may become a useful screening tool for hepatic encephalopathy in children. (orig.)

  7. Deep brain stimulation in the globus pallidus compensates response inhibition deficits: evidence from pantothenate kinase-associated neurodegeneration.

    Science.gov (United States)

    Mückschel, Moritz; Smitka, Martin; Hermann, Andreas; von der Hagen, Maja; Beste, Christian

    2016-05-01

    Fronto-striatal loops are important for many cognitive control processes, like response inhibition, and it has been suggested that the globus pallidus is of particular importance for these processes. In the current study, we investigate the effect of deep brain stimulation in the GP on response inhibition processes by means of neurophysiological (EEG) methods. We perform a case-control study in neuroaxonal dystrophy pantothenate kinase-associated neurodegeneration (PKAN) using single-case statistics. We control the signal-to-noise ratio of the EEG data. The data show that disease-related changes in the globus pallidus lead to dysfunctions in response inhibition processes. Dysfunctions in the GP seem to affect controlled, but not automatized behavior as evidenced by an increased rate of false alarms and attenuation of inhibition-related neurophysiological correlates. With respect to controlled behavior in terms of response inhibition, it seems that pre-motor subprocesses and not evaluation subprocesses are affected. Deep brain stimulation in the globus pallidus seems to be able to compensate the effects of disease-related changes in this structure and normalizes response inhibition performance and their electrophysiological correlates in PKAN.

  8. Childhood Laryngeal Dystonia Following Bilateral Globus Pallidus Abnormality: A Case Study and Review of Literature

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Saeedi Borujeni

    2017-01-01

    Full Text Available Introduction:Dystonia is a disorder of movement caused by various etiologies. Laryngeal dystonia is caused by the spasm of laryngeal muscles. It is a disorder caused by vocal fold movement in which excessive adduction or abduction of the vocal folds occurs during speech. The pathophysiology of this type of dystonia is not fully known. Some researchers have suggested that basal ganglia structures and their connections with cortical areas have been involved in the pathogenesis of dystonia. Case Report:In this paper a 7.5-year-old boy suffering from laryngeal dystonia with bilateral lesions in Globus Pallidus is presented. The patient also suffered from swallowing problems, monotone voice, vocal tremor, hypersensitivity of gag reflex, and stuttering. Drug treatment failed to cure him; therefore, he was referred to rehabilitation therapy.  Conclusion:In conclusion, special attention should be brought upon laryngeal dystonia, especially in patients showing Extra-pyramidal symptoms and/or abnormalities of the basal ganglia. In children, laryngeal dystonia may be potentially fatal. Lack of consideration for this condition during rehabilitation therapy can lead to serious consequences for a child.

  9. Involvement of human internal globus pallidus in the early modulation of cortical error-related activity.

    Science.gov (United States)

    Herrojo Ruiz, María; Huebl, Julius; Schönecker, Thomas; Kupsch, Andreas; Yarrow, Kielan; Krauss, Joachim K; Schneider, Gerd-Helge; Kühn, Andrea A

    2014-06-01

    The detection and assessment of errors are a prerequisite to adapt behavior and improve future performance. Error monitoring is afforded by the interplay between cortical and subcortical neural systems. Ample evidence has pointed to a specific cortical error-related evoked potential, the error-related negativity (ERN), during the detection and evaluation of response errors. Recent models of reinforcement learning implicate the basal ganglia (BG) in early error detection following the learning of stimulus-response associations and in the modulation of the cortical ERN. To investigate the influence of the human BG motor output activity on the cortical ERN during response errors, we recorded local field potentials from the sensorimotor area of the internal globus pallidus and scalp electroencephalogram representing activity from the posterior medial frontal cortex in patients with idiopathic dystonia (hands not affected) during a flanker task. In error trials, a specific pallidal error-related potential arose 60 ms prior to the cortical ERN. The error-related changes in pallidal activity-characterized by theta oscillations-were predictive of the cortical error-related activity as assessed by Granger causality analysis. Our findings show an early modulation of error-related activity in the human pallidum, suggesting that pallidal output influences the cortex at an early stage of error detection.

  10. Modeling Laterality of the Globus Pallidus Internus in Patients With Parkinson's Disease.

    Science.gov (United States)

    Sharim, Justin; Yazdi, Daniel; Baohan, Amy; Behnke, Eric; Pouratian, Nader

    2017-04-01

    Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization. © 2016 International Neuromodulation Society.

  11. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

    Science.gov (United States)

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

    2016-01-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  12. Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus

    International Nuclear Information System (INIS)

    O'Gorman, Ruth L.; Shmueli, Karin; Ashkan, Keyoumars; Selway, Richard P.; Samuel, Michael; Lythgoe, David J.; Shahidiani, Asal; Wastling, Stephen J.; Footman, Michelle; Jarosz, Jozef

    2011-01-01

    Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting. MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2 * mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed. SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN. SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting. (orig.)

  13. Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus

    Energy Technology Data Exchange (ETDEWEB)

    O' Gorman, Ruth L. [King' s College Hospital, Department of Neuroradiology, London (United Kingdom); University Children' s Hospital (Kinderspital), MR Zentrum, Zurich (Switzerland); Shmueli, Karin [National Institutes of Health, Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, MD (United States); Ashkan, Keyoumars; Selway, Richard P. [King' s College Hospital, Department of Neurosurgery, London (United Kingdom); Samuel, Michael [King' s College Hospital, Department of Neurology, London (United Kingdom); Lythgoe, David J.; Shahidiani, Asal [Institute of Psychiatry, Department of Clinical Neuroscience, London (United Kingdom); Wastling, Stephen J. [Institute of Psychiatry, Department of Clinical Neuroscience, London (United Kingdom); King' s College Hospital, Department of Medical Engineering and Physics, London (United Kingdom); Footman, Michelle [King' s College Hospital, Department of Medical Engineering and Physics, London (United Kingdom); Jarosz, Jozef [King' s College Hospital, Department of Neuroradiology, London (United Kingdom)

    2011-01-15

    Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting. MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2{sup *} mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed. SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN. SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting. (orig.)

  14. Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome.

    Directory of Open Access Journals (Sweden)

    Perminder S Sachdev

    Full Text Available BACKGROUND: We have previously reported the results of Deep Brain Stimulation (DBS of the antero-medial globus pallidus interna (GPi for severe Tourette Syndrome (TS in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months. METHODS: 17 patients (14 male; mean age 29.1 years, range 17-51 years with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8-46 months following surgery. RESULTS: Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6% patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1, transient anxiety (2, dizziness (1, poor balance (1 and worsening of stuttering (1. CONCLUSIONS: This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years.

  15. Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia.

    Directory of Open Access Journals (Sweden)

    Hye Ran Park

    Full Text Available GPi (Internal globus pallidus DBS (deep brain stimulation is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia.This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital.Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12-84.The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006. The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073. When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement.GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.

  16. Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity‐related temperaments in young healthy adults

    Science.gov (United States)

    Taki, Yasuyuki; Sekiguchi, Atsushi; Hashizume, Hiroshi; Nouchi, Rui; Sassa, Yuko; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Nakagawa, Seishu; Nagase, Tomomi; Kunitoki, Keiko; Kawashima, Ryuta

    2015-01-01

    Abstract Recent investigations revealed mean diffusivity (MD) in gray matter and white matter areas is correlated with individual cognitive differences in healthy subjects and show unique properties and sensitivity that other neuroimaging tools donot have. In this study, we tested the hypothesis that the MD in the dopaminergic system is associated with individual differences in verbal creativity measured by divergent thinking (VCDT) and novelty seeking based on prior studies suggesting associations between these and dopaminergic functions. We examined this issue in a large sample of right‐handed healthy young adults. We used analyses of MD and a psychological measure of VCDT, as well as personality measures of the Temperament and Character Inventory (TCI). Our results revealed associations between higher VCDT and lower MD in the bilateral globus pallidus. Furthermore, not only higher novelty seeking, but also lower harm avoidance, higher self‐directedness, and higher self‐transcendence were robustly associated with lower MD in the right globus pallidus, whereas higher persistence was associated with lower MD in the left globus pallidus. These personality variables were also associated with VCDT. The globus pallidus receives the dopaminergic input from the substantia nigra and plays a key role in motivation which is critically linked to dopamine. These results suggested the MD in the globus pallidus, underlie the association between VCDT and multiple personalities in TCI including novelty seeking. Hum Brain Mapp 36:1808–1827, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:25627674

  17. Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity-related temperaments in young healthy adults.

    Science.gov (United States)

    Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Hashizume, Hiroshi; Nouchi, Rui; Sassa, Yuko; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Nakagawa, Seishu; Nagase, Tomomi; Kunitoki, Keiko; Kawashima, Ryuta

    2015-05-01

    Recent investigations revealed mean diffusivity (MD) in gray matter and white matter areas is correlated with individual cognitive differences in healthy subjects and show unique properties and sensitivity that other neuroimaging tools donot have. In this study, we tested the hypothesis that the MD in the dopaminergic system is associated with individual differences in verbal creativity measured by divergent thinking (VCDT) and novelty seeking based on prior studies suggesting associations between these and dopaminergic functions. We examined this issue in a large sample of right-handed healthy young adults. We used analyses of MD and a psychological measure of VCDT, as well as personality measures of the Temperament and Character Inventory (TCI). Our results revealed associations between higher VCDT and lower MD in the bilateral globus pallidus. Furthermore, not only higher novelty seeking, but also lower harm avoidance, higher self-directedness, and higher self-transcendence were robustly associated with lower MD in the right globus pallidus, whereas higher persistence was associated with lower MD in the left globus pallidus. These personality variables were also associated with VCDT. The globus pallidus receives the dopaminergic input from the substantia nigra and plays a key role in motivation which is critically linked to dopamine. These results suggested the MD in the globus pallidus, underlie the association between VCDT and multiple personalities in TCI including novelty seeking. © 2015 Wiley Periodicals, Inc.

  18. High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted MR Images: Comparison between Gadobutrol and Linear Gadolinium-Based Contrast Agents.

    Science.gov (United States)

    Moser, F G; Watterson, C T; Weiss, S; Austin, M; Mirocha, J; Prasad, R; Wang, J

    2018-02-01

    In view of the recent observations that gadolinium deposits in brain tissue after intravenous injection, our aim of this study was to compare signal changes in the globus pallidus and dentate nucleus on unenhanced T1-weighted MR images in patients receiving serial doses of gadobutrol, a macrocyclic gadolinium-based contrast agent, with those seen in patients receiving linear gadolinium-based contrast agents. This was a retrospective analysis of on-site patients with brain tumors. Fifty-nine patients received only gadobutrol, and 60 patients received only linear gadolinium-based contrast agents. Linear gadolinium-based contrast agents included gadoversetamide, gadobenate dimeglumine, and gadodiamide. T1 signal intensity in the globus pallidus, dentate nucleus, and pons was measured on the precontrast portions of patients' first and seventh brain MRIs. Ratios of signal intensity comparing the globus pallidus with the pons (globus pallidus/pons) and dentate nucleus with the pons (dentate nucleus/pons) were calculated. Changes in the above signal intensity ratios were compared within the gadobutrol and linear agent groups, as well as between groups. The dentate nucleus/pons signal ratio increased in the linear gadolinium-based contrast agent group ( t = 4.215, P linear gadolinium-based contrast agent group ( t = 2.931, P linear gadolinium-based contrast agents. © 2018 by American Journal of Neuroradiology.

  19. Parkinson's disease outcomes after intraoperative CT-guided "asleep" deep brain stimulation in the globus pallidus internus.

    Science.gov (United States)

    Mirzadeh, Zaman; Chapple, Kristina; Lambert, Margaret; Evidente, Virgilio G; Mahant, Padma; Ospina, Maria C; Samanta, Johan; Moguel-Cobos, Guillermo; Salins, Naomi; Lieberman, Abraham; Tröster, Alexander I; Dhall, Rohit; Ponce, Francisco A

    2016-04-01

    Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording ortest stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson's disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following "asleep" deep brain stimulation in the globus pallidus internus (GPi). The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson's Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson's Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented. Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events. Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after

  20. Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

    Directory of Open Access Journals (Sweden)

    Chen Yang

    Full Text Available High-voltage spindles (HVSs have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1 in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

  1. Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease: An Institutional Experience and Review

    Directory of Open Access Journals (Sweden)

    Shazia Mirza

    2017-01-01

    Full Text Available Deep Brain Stimulation (DBS has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi and Subthalamic Nucleus (STN are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient’s profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute’s DBS paradigm to ensure that patients receive the optimal therapy.

  2. Effect of subthalamic nucleus or globus pallidus interna stimulation on oculomotor function in patients with Parkinson's disease.

    Science.gov (United States)

    Fridley, Jared; Adams, Gareth; Sun, Ping; York, Michelle; Atassi, Farah; Lai, Eugene; Simpson, Richard; Viswanathan, Ashwin; Yoshor, Daniel

    2013-01-01

    Deep brain stimulation (DBS) of either the globus pallidus interna (GPi) or subthalamic nucleus (STN) is similarly effective for treating somatomotor manifestations of Parkinson's disease (PD), but differences in how stimulation of each target affects oculomotor function are poorly understood. We sought to determine if stimulation of the STN, but not the GPi, affects oculomotor function in PD patients. Nineteen PD patients with DBS implants (8 bilateral GPi, 9 bilateral STN and 2 unilateral STN) were studied. Testing was performed with stimulation on, then off. Somatomotor function was tested using the Unified Parkinson's Disease Rating Scale (UPDRS) motor exam. For oculomotor testing, patients performed pro- and antisaccade tasks while monitored with an infrared eye tracker. Saccadic latency, saccadic intrusions, and square-wave jerks (SWJs) were measured for each trial. As expected, UPDRS motor scores improved with both GPi and STN stimulation. With GPi stimulation, there was no significant difference in oculomotor function with stimulation on or off. However, with STN stimulation on, there was a significant increase in the mean number of SWJs/s, as well as a significant decrease in latency for both pro- and antisaccade tasks. Stimulation of either GPi or STN had similar effects on somatomotor function, but only STN stimulation significantly altered oculomotor function. Copyright © 2013 S. Karger AG, Basel.

  3. Serial 1H-MRS of thalamus during deep brain stimulation of bilateral globus pallidus internus for primary generalized dystonia

    International Nuclear Information System (INIS)

    Chernov, Mikhail F.; Iseki, Hiroshi; Takakura, Kintomo; Ochiai, Taku; Taira, Takaomi; Hori, Tomokatsu; Ono, Yuko; Nakamura, Ryoichi; Muragaki, Yoshihiro

    2008-01-01

    The physiological mechanisms of deep brain stimulation (DBS) are not completely clear. Our understanding of them may be facilitated with the use of proton magnetic resonance spectroscopy ( 1 H-MRS). Serial 1 H-MRS of both thalami was performed during the course of DBS of bilateral globus pallidus internus in a patient with primary generalized dystonia. Two days after microelectrode implantation, a pulse frequency of 185 Hz was applied for stimulation. It resulted in relief of symptoms and a decrease of Burke-Fahn-Marsden dystonia rating scale (BFMDRS) scores, and was accompanied by a prominent increase of N-acetylaspartate (NAA)/choline-containing compounds (Cho) ratio, a mild increase of NAA/creatine (Cr) ratio, and a moderate decrease of Cho/Cr ratio. Two weeks later, for a search of the optimal stimulation mode, the pulse frequency was switched to 60 Hz, which resulted in clinical deterioration and significant increase of BFMDRS scores. At that time, all investigated 1 H-MRS-detected metabolic parameters had nearly returned to the pretreatment levels. Use of serial 1 H-MRS investigations of various brain structures during DBS in cases of movement disorders permits detailed evaluation of the treatment response, has a potential for its possible prediction, and may facilitate understanding of the physiological mechanisms of stimulation. (orig.)

  4. An Asian Patient with Myoclonus-Dystonia (DYT11 Responsive to Deep Brain Stimulation of the Globus Pallidus Internus

    Directory of Open Access Journals (Sweden)

    Akinori Uruha

    2014-01-01

    Full Text Available We describe the case of a 42-year-old Japanese woman with childhood-onset myoclonus, dystonia, and psychiatric symptoms, including anxiety, phobia, and exaggerated startle response. The diagnosis was confirmed as myoclonus-dystonia (DYT11 by identifying a mutation in the gene encoding ε-sarcoglycan. Interestingly, while motor-related symptoms in DYT11 generally improve with alcohol ingestion, the patient’s symptoms were exacerbated by alcohol intake. Her severe and medically intractable symptoms were alleviated by bilateral deep brain stimulation of the globus pallidus internus, with myoclonus and dystonia scores showing 70% improvement after the surgery compared to presurgical scores. This is the first report of a genetically confirmed case of DYT11 in Japan. This paper together with other recent reports collectively demonstrates that DYT11 patients are distributed worldwide, including Asia. Thus, a diagnosis of DYT11 should be considered when clinicians encounter a patient with childhood-onset myoclonus and/or dystonia with psychiatric symptoms, regardless of ethnic background.

  5. Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or subthalamic nucleus deep brain stimulation for Parkinson's disease.

    Science.gov (United States)

    Boel, Judith A; Odekerken, Vincent J J; Schmand, Ben A; Geurtsen, Gert J; Cath, Danielle C; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J; Schuurman, P Richard; de Bie, Rob M A

    2016-12-01

    Effects on non-motor symptoms, mainly cognitive and psychiatric side effects, could influence the decision for either globus pallidus pars interna (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with Parkinson's disease (PD). 1) To compare cognitive and psychiatric outcomes 3 years after GPi DBS versus STN DBS, and 2) to report on occurrence of suicidal ideation, psychiatric diagnoses, social functioning, and marital satisfaction 3 years after DBS. Patients were randomized to receive GPi DBS (n = 65) or STN DBS (n = 63). Standardized assessments were performed at baseline, 1 year, and 3 years. We used linear mixed model analyses to investigate between-group differences on the Mattis Dementia Rating Scale (MDRS), neuropsychological tests, and psychiatric questionnaires 3 years after DBS. Eighty-seven patients (68%) completed at least one neuropsychological test after 3 years. No significant between-group differences were found on the MDRS (p = 0.61), neuropsychological tests (p-values between 0.17 and 0.87), and psychiatric questionnaires (p-values between 0.23 and 0.88) 3 years after DBS. The Mini International Neuropsychiatric Interview did not indicate a substantial number of psychiatric diagnoses after 3 years. Social functioning and marital satisfaction were comparable in both groups. Three years after GPi DBS and STN DBS no pronounced between-group differences on measures of cognitive and psychiatric functioning could be demonstrated. Overall, cognitive and psychiatric outcome 3 years after DBS do not provide a clear direction for clinicians when considering which of these two surgical targets to choose. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease.

    Science.gov (United States)

    Liu, Yi; Li, Weina; Tan, Changhong; Liu, Xi; Wang, Xin; Gui, Yuejiang; Qin, Lu; Deng, Fen; Hu, Changlin; Chen, Lifen

    2014-09-01

    Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi) and the subthalamic nucleus (STN) are commonly targeted by this procedure. The purpose of this meta-analysis was to compare the efficacy of DBS in each region. MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were searched for English-language studies published before April 2013. of studies investigating the efficacy and clinical outcomes of DBS of the GPi and STN for PD were analyzed. Six eligible trials containing a total of 563 patients were included in the analysis. Deep brain stimulation of the GPi or STN equally improved motor function, measured by the Unified Parkinson's Disease Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off-medication phases), within 1 year postsurgery. The change score for the on-medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518 patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p > 0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living) scores for patients on medication improved equally in both DBS groups (p = 0.97). STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27-316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by Beck Depression Inventory, 2nd edition scores, showed greater improvement from baseline after GPi DBS than after STN DBS (standardized mean difference -2.28, 95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). GPi and STN DBS improve motor function and activities of daily living for PD patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long

  7. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

    International Nuclear Information System (INIS)

    Stojanov, Dragan A.; Aracki-Trenkic, Aleksandra; Vojinovic, Slobodan; Ljubisavljevic, Srdjan; Benedeto-Stojanov, Daniela

    2016-01-01

    To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. (orig.)

  8. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan A. [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Clinical Center Nis, Center for Radiology, Nis (Serbia); Vojinovic, Slobodan; Ljubisavljevic, Srdjan [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Clinic for Neurology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-03-15

    To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. (orig.)

  9. Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Houchun H.; Pokorney, Amber; Towbin, Richard B.; Miller, Jeffrey H. [Phoenix Children' s Hospital, Department of Medical Imaging and Radiology, Phoenix, AZ (United States)

    2016-10-15

    Recent reports have suggested residual gadolinium deposition in the brain in subjects undergoing multiple contrast-enhanced MRI exams. These findings have raised some concerns regarding gadolinium-based contrast agent (GBCA) usage and retention in brain tissues. To summarize findings of hyperintense brain structures on precontrast T1-weighted images in 21 children undergoing multiple GBCA MRI exams. This retrospective study involved 21 patients, each of whom received multiple MRI examinations (range: 5-37 exams) with GBCA over the course of their medical treatment (duration from first to most recent exam: 1.2-12.9 years). The patients were between 0.9 and 14.4 years of age at the time of their first GBCA exam. Regions of interest were drawn in the dentate nucleus and the globus pallidus on 2-D fast spin echo images acquired at 1.5 T. The signal intensities of these two structures were normalized by that of the corpus callosum genu. Signal intensity ratios from these patients were compared to control patients of similar ages who have never received GBCA. Signal intensity ratios increased between the first and the most recent MRI exam in all 21 patients receiving GBCA, with an increase of 18.6%±12.7% (range: 0.5% to 47.5%) for the dentate nucleus and 12.4%±7.4% (range: -1.2% to 33.7%) for the globus pallidus (P<0.0001). Signal intensity ratios were also higher in GBCA patients than in controls (P<0.01). The degree of signal intensity enhancement did not correlate with statistical significance to the cumulative number or volume of GBCA administrations each patient received, the patient's age or the elapsed time between the first and most recent GBCA MRI exams. These results in children are consistent with recent findings in adults, suggesting possible gadolinium deposition in the brain. (orig.)

  10. Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children

    Energy Technology Data Exchange (ETDEWEB)

    Rossi Espagnet, Maria Camilla; Bernardi, Bruno; Figa-Talamanca, Lorenzo [Ospedale Pediatrico Bambino Gesu, IRCCS, Neuroradiology Unit, Imaging Department, Rome (Italy); Pasquini, Luca [Ospedale Pediatrico Bambino Gesu, IRCCS, Neuroradiology Unit, Imaging Department, Rome (Italy); University Sapienza, Neuroradiology Unit, Azienda Ospedaliera Sant' Andrea, Rome (Italy); Toma, Paolo [Ospedale Pediatrico Bambino Gesu, IRCCS, Department of Imaging, Rome (Italy); Napolitano, Antonio [Ospedale Pediatrico Bambino Gesu, IRCCS, Enterprise Risk Management, Medical Physics Department, Rome (Italy)

    2017-09-15

    Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naive patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children. (orig.)

  11. Holmes’ Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus

    Directory of Open Access Journals (Sweden)

    Sabri Aydın

    2017-05-01

    Full Text Available A 21-year-old male was admitted with severe right arm and hand tremors after a thalamic hemorrhage caused by a traffic accident. He was also suffering from agonizing pain in his right shoulder that manifested after the tremor. Neurologic examination revealed a disabling, severe, and irregular kinetic and postural tremor in the right arm during target-directed movements. There was also an irregular ipsilateral rest tremor and dystonic movements in the distal part of the right arm. The amplitude was moderate at rest and extremely high during kinetic and intentional movements. The patient underwent left globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. The patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating Scale and Visual Analog Scale six months after surgery.

  12. Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Conte, Giorgio; Minotti, Marta; De Piano, Francesca [Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Preda, Lorenzo [Universita degli Studi di Pavia, Department of Clinical-Surgical Diagnostic and Pediatric Sciences, Pavia (Italy); National Center of Oncological Hadrontherapy (CNAO Foundation), Division of Radiology, Pavia (Italy); Cocorocchio, Emilia; Ferrucci, Pier Francesco [European Institute of Oncology, Melanoma and Sarcoma Medical Oncology Division, Milan (Italy); Raimondi, Sara [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Giannitto, Caterina; Petralia, Giuseppe [European Institute of Oncology, Division of Radiology, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Division of Radiology, Milan (Italy); Universita degli Studi di Milano, Oncology and Haematology/Oncology Department, Milan (Italy)

    2017-10-15

    To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. We retrospectively included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. (orig.)

  13. Deep Brain Stimulation of the Internal Globus Pallidus Improves Response Initiation and Proactive Inhibition in Patients With Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Yixin Pan

    2018-04-01

    Full Text Available Background: Impulse control disorder is not uncommon in patients with Parkinson’s disease (PD who are treated with dopamine replacement therapy and subthalamic deep brain stimulation (DBS. Internal globus pallidus (GPi-DBS is increasingly used, but its role in inhibitory control has rarely been explored. In this study, we evaluated the effect of GPi-DBS on inhibitory control in PD patients.Methods: A stop-signal paradigm was used to test response initiation, proactive inhibition, and reactive inhibition. The subjects enrolled in the experiment were 27 patients with PD, of whom 13 had received only drug treatment and 14 had received bilateral GPi-DBS in addition to conventional medical treatment and 15 healthy individuals.Results: Our results revealed that with GPi-DBS on, patients with PD showed significantly faster responses than the other groups in trials where it was certain that no stop signal would be presented. Proactive inhibition was significantly different in the surgical patients with GPi-DBS on versus when GPi-DBS was off, in surgical patients with GPi-DBS on versus drug-treated patients, and in healthy controls versus drug-treated patients. Correlation analyses revealed that when GPi-DBS was on, there was a statistically significant moderate positive relationship between proactive inhibition and dopaminergic medication.Conclusion: GPi-DBS may lead to an increase in response initiation speed and improve the dysfunctional proactive inhibitory control observed in PD patients. Our results may help us to understand the role of the GPi in cortical-basal ganglia circuits.

  14. Constant-Current Deep Brain Stimulation of the Globus Pallidus Internus in the Treatment of Primary Dystonia by a Novel 8-Contact (Octrode) Lead.

    Science.gov (United States)

    Sakas, Damianos E; Leonardos, Athanassios; Boviatsis, Efstathios; Gatzonis, Stergios; Panourias, Ioannis; Stathis, Pantelis; Stavrinou, Lampis C

    2017-07-01

    To evaluate bilateral constant-current globus pallidus internus (GPi) deep brain stimulation using an 8-contact lead. This prospective, open-label, single-center pilot study of 10 patients assessed the feasibility of delivering bilaterally constant-current GPi deep brain stimulation with a novel 8-channel lead to treat primary dystonia using standard scales as outcome measures. Patients included 4 men and 6 women with a mean age of 35.8 years ± 9.2 (range, 27-49 years). Mean age of onset was 18.5 years ± 9.1 (range, 8-35 years), and mean disease duration was 17.3 years (range, 7-27 years). All had primary dystonia (8 generalized dystonia, 1 segmental dystonia, 1 focal dystonia). The primary variable was determined as 50% reduction in dystonia symptoms from baseline to the 6-month follow-up, as defined by the Burke-Fahn-Marsden Dystonia Rating Scale. Six patients (60.0%) achieved >50% reduction in Burke-Fahn-Marsden Dystonia Rating Scale score and were classified as responders at the 6-month follow-up. Five of these 6 responders (83.3%) sustained that response through the assessment at the end of the first year. Constant-current stimulation was associated with significant improvement in pain and quality of life in all patients. Nearly 84% of the overall improvement occurred by the end of first month after stimulation onset, documenting an early response to treatment. Axial symptoms responded the best. Constant-current GPi deep brain stimulation proved safe and efficacious for treatment of primary dystonia. Motor scores improved by 54%, mostly within the first month. No phenotype-specific stimulation could be achieved, despite the capability of the new lead to stimulate specific loci within the GPi. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Bilateral globus pallidus infarcts in ecstasy use

    OpenAIRE

    De Smet, K; De Maeseneer, M; Talebian, Y A; Stadnik, T; De Mey, J

    2011-01-01

    A 41-year-old man was found unconscious at his home by a friend. He was immediately admitted to the hospital through the emergency department. At the emergency department he regained consciousness. He mentionned he had a few alcoholic beverages the night before but otherwise clinical history was negative. On physical examination swelling of the right orbital area was evident. Further clinical history and laboratory tests were unremarkable. CT scan of the brain showed the right periorbital swe...

  16. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    International Nuclear Information System (INIS)

    Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

    2002-01-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  17. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

    2002-04-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  18. Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass

    Science.gov (United States)

    Menegas, William; Bergan, Joseph F; Ogawa, Sachie K; Isogai, Yoh; Umadevi Venkataraju, Kannan; Osten, Pavel; Uchida, Naoshige; Watabe-Uchida, Mitsuko

    2015-01-01

    Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense ‘clusters’ of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs. DOI: http://dx.doi.org/10.7554/eLife.10032.001 PMID:26322384

  19. Management of Globus Pharyngeus

    Directory of Open Access Journals (Sweden)

    S. Kortequee

    2013-01-01

    Full Text Available Globus pharyngeus is a common ENT condition. This paper reviews the current evidence on globus and gives a rational guide to the management of patients with globus. The aetiology of globus is still unclear though most ENT surgeons believe that reflux whether acidic or not plays a significant role. Though proton pump inhibitors are used extensively in practice, there is little evidence to support their efficacy. Most patients with globus can be discharged after simple office investigations. The role of pepsin-induced laryngeal injury is an exciting concept that needs further study. Given the benign nature of globus pharyngeus, in most cases, reassurance rather than treatment or extensive investigation with rigid oesophagoscopy or contrast swallows is all that is needed. We need more research into the aetiology of globus.

  20. A multivariate surface-based analysis of the putamen in premature newborns: regional differences within the ventral striatum.

    Directory of Open Access Journals (Sweden)

    Jie Shi

    Full Text Available Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity

  1. Globus | Informatics Technology for Cancer Research (ITCR)

    Science.gov (United States)

    Globus software services provide secure cancer research data transfer, synchronization, and sharing in distributed environments at large scale. These services can be integrated into applications and research data gateways, leveraging Globus identity management, single sign-on, search, and authorization capabilities. Globus Genomics integrates Globus with the Galaxy genomics workflow engine and Amazon Web Services to enable cancer genomics analysis that can elastically scale compute resources with demand.

  2. Changes in /sup 3/H-substance P receptor binding in the rat brain after kainic acid lesion of the corpus striatum

    Energy Technology Data Exchange (ETDEWEB)

    Mantyh, P.W.; Hunt, S.P.

    1986-06-01

    Previous studies have indicated that the substantia nigra contains the highest concentration of substance P-like immunoreactivity (SPLI) in the brain. Paradoxically, it also appears to contain one of the lowest concentrations of substance P receptors in the brain. One possibility is that the massive amount of SPLI blocks the binding of the radioligand to the substance P receptor and/or down-regulates the number of substance P receptors present in this structure. Since greater than 95% of the SPLI within the substantia nigra originates from the corpus striatum, we have lesioned this area and measured the changes in substance P receptor concentration in the substantia nigra and other corpus striatal projection areas. A semiquantitative autoradiographic technique for measuring the binding of /sup 3/H-substance P to substance P receptors was used in conjunction with tritium-sensitive film. 3H-substance P binding was measured in both the corpus striatum and its projection areas after kainic acid lesion of the corpus striatum. At either 4 or 21 d after the lesion there was approximately a 90% loss of substance P receptors in the rostral striatum, a 74% loss in the globus pallidus, a 57% increase in receptor number in lamina I and II of the ipsilateral somatosensory cortex, and no apparent change in the number of receptors in the substantia nigra pars reticulata, superior colliculus, and central gray. These findings suggest that the low concentration of substance P receptors found within the substantia nigra is not due the massive SPLI innervation, since removal of greater than 95% of the SPLI had no measurable effect on the concentration of substance P receptors.

  3. Efficient digital implementation of a conductance-based globus pallidus neuron and the dynamics analysis

    Science.gov (United States)

    Yang, Shuangming; Wei, Xile; Deng, Bin; Liu, Chen; Li, Huiyan; Wang, Jiang

    2018-03-01

    Balance between biological plausibility of dynamical activities and computational efficiency is one of challenging problems in computational neuroscience and neural system engineering. This paper proposes a set of efficient methods for the hardware realization of the conductance-based neuron model with relevant dynamics, targeting reproducing the biological behaviors with low-cost implementation on digital programmable platform, which can be applied in wide range of conductance-based neuron models. Modified GP neuron models for efficient hardware implementation are presented to reproduce reliable pallidal dynamics, which decode the information of basal ganglia and regulate the movement disorder related voluntary activities. Implementation results on a field-programmable gate array (FPGA) demonstrate that the proposed techniques and models can reduce the resource cost significantly and reproduce the biological dynamics accurately. Besides, the biological behaviors with weak network coupling are explored on the proposed platform, and theoretical analysis is also made for the investigation of biological characteristics of the structured pallidal oscillator and network. The implementation techniques provide an essential step towards the large-scale neural network to explore the dynamical mechanisms in real time. Furthermore, the proposed methodology enables the FPGA-based system a powerful platform for the investigation on neurodegenerative diseases and real-time control of bio-inspired neuro-robotics.

  4. Mossbauer and SQUID Characterization of Iron in Human Tissue: Case of Globus Pallidus

    Czech Academy of Sciences Publication Activity Database

    Miglierini, M.; Boca, R.; Kopáni, M.; Lančok, Adriana

    2014-01-01

    Roč. 126, č. 1 (2014), s. 240-241 ISSN 0587-4246 R&D Projects: GA ČR GAP204/10/0035 Institutional support: RVO:61388980 Keywords : FERRITIN Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.530, year: 2014

  5. Correlation between Relaxometry and Diffusion Tensor Imaging in the Globus Pallidus of Huntington's Disease Patients

    Czech Academy of Sciences Publication Activity Database

    Syka, Michael; Keller, J.; Klempíř, J.; Rulseh, A. M.; Roth, J.; Jech, R.; Voříšek, Ivan; Vymazal, J.

    2015-01-01

    Roč. 10, č. 3 (2015), e0118907 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP303/11/2378 Institutional support: RVO:68378041 Keywords : basal ganglia * gray-matter * human brain Subject RIV: FH - Neurology Impact factor: 3.057, year: 2015

  6. Involvement of the subthalamic nucleus and globus pallidus internus in attention

    Czech Academy of Sciences Publication Activity Database

    Bocková, M.; Chládek, Jan; Jurák, Pavel; Halámek, Josef; Baláž, M.; Rektor, I.

    2011-01-01

    Roč. 118, č. 8 (2011), s. 1235-1245 ISSN 0300-9564 R&D Projects: GA AV ČR IAA200650801; GA MŠk ED0017/01/01 Institutional research plan: CEZ:AV0Z20650511 Keywords : basal ganglia * ERP * ERD/S * attention * DBS Subject RIV: FH - Neurology Impact factor: 2.730, year: 2011

  7. Globus

    Science.gov (United States)

    ... Volvulus Rare Diseases Abdominal Adhesions Anal Fistulas Celiac Disease Clostridium Difficile Congenital Sucrase-Isomaltase Deficiency (CSID) Diverticulosis and Diverticulitis Diverticula, Diverticulosis, Diverticulitis: What's the Difference? Nuts, Seeds, ...

  8. Psychological Distress in Patients having Globus Pharyngeus

    Directory of Open Access Journals (Sweden)

    Anup Acharya

    2014-12-01

    group. The patient who present with Globus should undergo psychiatric evaluation after organic causes have been ruled out. We recommend a national policy to evaluate the population for their psychiatric health.

  9. Application experiences with the Globus toolkit.

    Energy Technology Data Exchange (ETDEWEB)

    Brunett, S.

    1998-06-09

    The Globus grid toolkit is a collection of software components designed to support the development of applications for high-performance distributed computing environments, or ''computational grids'' [14]. The Globus toolkit is an implementation of a ''bag of services'' architecture, which provides application and tool developers not with a monolithic system but rather with a set of stand-alone services. Each Globus component provides a basic service, such as authentication, resource allocation, information, communication, fault detection, and remote data access. Different applications and tools can combine these services in different ways to construct ''grid-enabled'' systems. The Globus toolkit has been used to construct the Globus Ubiquitous Supercomputing Testbed, or GUSTO: a large-scale testbed spanning 20 sites and included over 4000 compute nodes for a total compute power of over 2 TFLOPS. Over the past six months, we and others have used this testbed to conduct a variety of application experiments, including multi-user collaborative environments (tele-immersion), computational steering, distributed supercomputing, and high throughput computing. The goal of this paper is to review what has been learned from these experiments regarding the effectiveness of the toolkit approach. To this end, we describe two of the application experiments in detail, noting what worked well and what worked less well. The two applications are a distributed supercomputing application, SF-Express, in which multiple supercomputers are harnessed to perform large distributed interactive simulations; and a tele-immersion application, CAVERNsoft, in which the focus is on connecting multiple people to a distributed simulated world.

  10. Globus: Service and Platform for Research Data Lifecycle Management

    Science.gov (United States)

    Ananthakrishnan, R.; Foster, I.

    2017-12-01

    Globus offers a range of data management capabilities to the community as hosted services, encompassing data transfer and sharing, user identity and authorization, and data publication. Globus capabilities are accessible via both a web browser and REST APIs. Web access allows researchers to use Globus capabilities through a software-as-a-service model; and the REST APIs address the needs of developers of research services, who can now use Globus as a platform, outsourcing complex user and data management tasks to Globus services. In this presentation, we review Globus capabilities and outline how it is being applied as a platform for scientific services, and highlight work done to link computational analysis flows to the underlying data through an interactive Jupyter notebook environment to promote immediate data usability, reusability of these flows by other researchers, and future analysis extensibility.

  11. Epiglottic cyst as an etiological factor of globus sensation.

    Science.gov (United States)

    Polat, Bahtiyar; Karahatay, Serdar; Gerek, Mustafa

    2015-09-01

    Globus is a subjective complaint that describes a sensation of a lump or a foreign body in the throat. Despite being a well-known and common clinical condition, the etiological factors have not been definitely elucidated yet. The study was set up to ascertain the relationship between epiglottic cysts and globus sensation. All patients undergoing investigation and treatments for globus sensation were included in the study. Patients with epiglottic cysts but no other possible causes of globus sensation were constituted the series of patients. Patients were asked to assess the levels of complaint before and after the carbon dioxide (CO2) laser excisions of the cysts. Epiglottic cysts were found in 10 (5.4%) of the 182 patients. Three of these 10 patients who had concomitant diseases or conditions that may cause globus sensation and one patient who refused the surgery were excluded from the study. All the remaining six patients reported relief of the globus sensation after the CO2 laser excisions of the cysts. Our results, obtained from this limited series, indicated that epiglottic cysts may be considered as one of the etiological factors of globus sensation.

  12. Basketball training increases striatum volume.

    Science.gov (United States)

    Park, In Sung; Lee, Kea Joo; Han, Jong Woo; Lee, Nam Joon; Lee, Won Teak; Park, Kyung Ah; Rhyu, Im Joo

    2011-02-01

    The striatum is associated with the learning and retention of motor skills. Several studies have shown that motor learning induces neuronal changes in the striatum. We investigated whether macroscopic change in striatum volume occurs in a segment of the human population who learned basketball-related motor skills and practiced them throughout their entire athletic life. Three-dimensional magnetic resonance imaging volumetry was performed in basketball players and healthy controls, and striatum volumes were compared based on basketball proficiency, region and side. We identified morphological enlargement in the striatum of basketball players in comparison with controls. Our results suggest that continued practice and repetitive performance of basketball-related motor skills may induce plastic structural changes in the human striatum. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Reclassification of Geobacillus pallidus (Scholz et al. 1988) Banat et al. 2004 as Aeribacillus pallidus gen. nov., comb. nov.

    Science.gov (United States)

    Miñana-Galbis, David; Pinzón, Dora L; Lorén, J Gaspar; Manresa, Angels; Oliart-Ros, Rosa M

    2010-07-01

    Although Anoxybacillus and Geobacillus, two genera of thermophilic bacteria close to the genus Bacillus, have only been described recently, the number of species in these genera has increased rapidly. Four thermophilic, lipolytic strains (DR01, DR02, DR03 and DR04) isolated from a hot spring in Veracruz (Mexico), which could not be identified phenotypically, were subjected to 16S rRNA gene sequence analysis. Three strains were identified as belonging to the genus Anoxybacillus, but strain DR03 was identified as Geobacillus pallidus. This result led us to perform a phylogenetic analysis of the genera Anoxybacillus and Geobacillus based on 16S rRNA gene sequences from all the type strains of these genera. Phylogenetic trees showed three major clusters, Anoxybacillus-Geobacillus tepidamans, Geobacillus sensu stricto and Geobacillus pallidus, while the 16S rRNA gene sequences of G. pallidus (DR03 and the type strain) showed low similarity to sequences of Anoxybacillus (92.5-95.1 %) and Geobacillus (92.8-94.5 %) species, as well as to Bacillus subtilis (92.2-92.4 %). In addition, G. pallidus could be differentiated from Anoxybacillus and Geobacillus on the basis of DNA G+C content and fatty acid and polar lipid profiles. From these results, it is proposed that Geobacillus pallidus should be classified in a novel genus, for which we propose the name Aeribacillus, as Aeribacillus pallidus gen. nov., comb. nov. The type strain of Aeribacillus pallidus is H12(T) (=ATCC 51176(T) =DSM 3670(T) =LMG 19006(T)).

  14. Histamine and the striatum.

    Science.gov (United States)

    Bolam, J Paul; Ellender, Tommas J

    2016-07-01

    The neuromodulator histamine is released throughout the brain during periods of wakefulness. Combined with an abundant expression of histamine receptors, this suggests potential widespread histaminergic control of neural circuit activity. However, the effect of histamine on many of these circuits is unknown. In this review we will discuss recent evidence for histaminergic modulation of the basal ganglia circuitry, and specifically its main input nucleus; the striatum. Furthermore, we will discuss recent findings of histaminergic dysfunction in several basal ganglia disorders, including in Parkinson's disease and most prominently, in Tourette's syndrome, which has led to a resurgence of interest in this neuromodulator. Combined, these recent observations not only suggest a central role for histamine in modulating basal ganglia activity and behaviour, but also as a possible target in treating basal ganglia disorders. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Globus Platform-as-a-Service for Collaborative Science Applications.

    Science.gov (United States)

    Ananthakrishnan, Rachana; Chard, Kyle; Foster, Ian; Tuecke, Steven

    2015-02-01

    Globus, developed as Software-as-a-Service (SaaS) for research data management, also provides APIs that constitute a flexible and powerful Platform-as-a-Service (PaaS) to which developers can outsource data management activities such as transfer and sharing, as well as identity, profile and group management. By providing these frequently important but always challenging capabilities as a service, accessible over the network, Globus PaaS streamlines web application development and makes it easy for individuals, teams, and institutions to create collaborative applications such as science gateways for science communities. We introduce the capabilities of this platform and review representative applications.

  16. Pregnancy and Delivery in a Generalized Dystonia Patient Treated with Internal Globus Pallidal Deep Brain Stimulation: a Case Report.

    Science.gov (United States)

    Park, Hye Ran; Lee, Jae Meen; Park, Hyeyoung; Shin, Chae Won; Kim, Han Joon; Park, Hee Pyoung; Kim, Dong Gyu; Jeon, Beom Seok; Paek, Sun Ha

    2017-01-01

    Internal globus pallidus (GPi) deep brain stimulation (DBS) has been widely accepted as an effective treatment modality of medically refractory dystonia. However, there have been few studies regarding the safety issue of pregnancy and childbirth related with DBS. This report describes a female patient who was pregnant and delivered a baby after GPi DBS surgery. A 33-year-old female patient with acquired generalized dystonia underwent bilateral GPi DBS implantation. She obtained considerable improvement in both movement and disability after DBS implantation. Four years later, she was pregnant and the obstetricians consulted us about the safety of the delivery. At 38-weeks into pregnancy, a scheduled caesarian section was carried out under general anesthesia. After induction using thiopental and succinylcholine, intubation was done quickly, followed by DBS turn off. For hemostasis, only bipolar electrocautery was used. Before awakening from the anesthesia, DBS was turned on as the same parameters previously adjusted. After delivery, she could feed her baby by herself, because the dystonia of left upper extremity and hand was improved. Until now, she has been showing continual improvement and being good at housework, carrying for children, with no trouble in daily life. This observation indicates that the patients who underwent DBS could safely be pregnant and deliver a baby.

  17. New results from Globus-M spherical tokamak

    International Nuclear Information System (INIS)

    Gusev, V.K.

    2002-01-01

    New results from Globus-M spherical tokamak (ST) are presented. Reported are the achievements of high plasma current of 0.36 MA and high toroidal magnetic field of 0.55 T. Plasma column stability in Globus-M is conserved at low edge safety factors and high plasma densities. Achieved lowest safety factor was q(cyl) 19 m -3 . New methods of density increase are discussed. Low-density boarder of operational space is investigated. Runaway electrons properties and conditions of their generation are investigated. Results look promising for STs. Plasma-wall interaction study was performed. Silicon probes were installed into vacuum vessel. They were exposed to boronization, first, and then deposited film interacted with plasma. Discussed are film properties. Briefly described are new diagnostic tools installed on tokamak. Status and preliminary results obtained with auxiliary heating systems are shown. (author)

  18. Deploying HEP applications using Xen and Globus Virtual Workspaces

    International Nuclear Information System (INIS)

    Agarwal, A; Desmarais, R; Gable, I; Grundy, D; P-Brown, D; Seuster, R; Vanderster, D C; Sobie, R; Charbonneau, A; Enge, R

    2008-01-01

    The deployment of HEP applications in heterogeneous grid environments can be challenging because many of the applications are dependent on specific OS versions and have a large number of complex software dependencies. Virtual machine monitors such as Xen could be used to package HEP applications, complete with their execution environments, to run on resources that do not meet their operating system requirements. Our previous work has shown HEP applications running within Xen suffer little or no performance penalty as a result of virtualization. However, a practical strategy is required for remotely deploying, booting, and controlling virtual machines on a remote cluster. One tool that promises to overcome the deployment hurdles using standard grid technology is the Globus Virtual Workspaces project. We describe strategies for the deployment of Xen virtual machines using Globus Virtual Workspace middleware that simplify the deployment of HEP applications

  19. Monitoring the grid with the Globus Toolkit MDS4

    International Nuclear Information System (INIS)

    Schopf, Jennifer M; Pearlman, Laura; Miller, Neill; Kesselman, Carl; Foster, Ian; D'Arcy, Mike; Chervenak, Ann

    2006-01-01

    The Globus Toolkit Monitoring and Discovery System (MDS4) defines and implements mechanisms for service and resource discovery and monitoring in distributed environments. MDS4 is distinguished from previous similar systems by its extensive use of interfaces and behaviors defined in the WS-Resource Framework and WS-Notification specifications, and by its deep integration into essentially every component of the Globus Toolkit. We describe the MDS4 architecture and the Web service interfaces and behaviors that allow users to discover resources and services, monitor resource and service states, receive updates on current status, and visualize monitoring results. We present two current deployments to provide insights into the functionality that can be achieved via the use of these mechanisms

  20. Using Globus to Transfer and Share Big Data | Poster

    Science.gov (United States)

    By Ashley DeVine, Staff Writer, and Mark Wance, Guest Writer; photo by Richard Frederickson, Staff Photographer Editor's note: This article was updated April 30, 2018. Transferring big data, such as the genomics data delivered to customers from the Center for Cancer Research Sequencing Facility (CCR SF), has been difficult in the past because the transfer systems have not kept pace with the size of the data. However, the situation is changing as a result of the Globus project.

  1. [Use of high frequency cinematography in diagnosis of globus sensation].

    Science.gov (United States)

    Alberty, J; Oelerich, M

    1996-09-01

    Globus pharyngis is a frequent symptom in patients who consult an otolaryngologist. In many cases, routine diagnostic work-up including history, clinical examination, and barium swallow fail to revealing the underlying pathogenesis. In a retrospective study, we present 51 selected patients suffering from globus pharyngis of unknown origin who were investigated by high-speed cineradiography in a standardized manner. Twenty-four of the patients enrolled in the study (47.1%) showed functional and/or structural swallowing disorders. In 13 cases (25.5%) dyskinesias of the superior esophagus sphincter muscle were found. Five of these patients (9.8%) also had an inconstant hypopharyngeal diverticulum. Six cases (11.8%) showed laryngeal penetration or tracheal aspiration. In four cases (7.8%) functional disorders of pharyngeal, and in three cases (5.9%) functional disorders of oral bolus transport were found. Furthermore one hypopharyngeal web (1.9%) and two benign tumors (3.9%) were detected. In many cases, varying combinations of these findings occurred. Using high-speed cineradiography for evaluation of globus pharyngis results in an increased incidence of pathologic findings, and thus is an important method for interdisciplinary diagnostic work up of patients suffering from this symptom.

  2. Globus Online: Climate Data Management for Small Teams

    Science.gov (United States)

    Ananthakrishnan, R.; Foster, I.

    2013-12-01

    Large and highly distributed climate data demands new approaches to data organization and lifecycle management. We need, in particular, catalogs that can allow researchers to track the location and properties of large numbers of data files, and management tools that can allow researchers to update data properties and organization during their research, move data among different locations, and invoke analysis computations on data--all as easily as if they were working with small numbers of files on their desktop computer. Both catalogs and management tools often need to be able to scale to extremely large quantities of data. When developing solutions to these problems, it is important to distinguish between the needs of (a) large communities, for whom the ability to organize published data is crucial (e.g., by implementing formal data publication processes, assigning DOIs, recording definitive metadata, providing for versioning), and (b) individual researchers and small teams, who are more frequently concerned with tracking the diverse data and computations involved in what highly dynamic and iterative research processes. Key requirements in the latter case include automated data registration and metadata extraction, ease of update, close-to-zero management overheads (e.g., no local software install); and flexible, user-managed sharing support, allowing read and write privileges within small groups. We describe here how new capabilities provided by the Globus Online system address the needs of the latter group of climate scientists, providing for the rapid creation and establishment of lightweight individual- or team-specific catalogs; the definition of logical groupings of data elements, called datasets; the evolution of catalogs, dataset definitions, and associated metadata over time, to track changes in data properties and organization as a result of research processes; and the manipulation of data referenced by catalog entries (e.g., replication of a dataset to

  3. New results from the Globus-M spherical tokamak

    International Nuclear Information System (INIS)

    Gusev, V.K.; Ananiev, A.S.; Amoskov, V.M.

    2003-01-01

    New results from the Globus-M spherical tokamak are presented. High plasma current of 0.36 MA, high toroidal magnetic field of 0.55 T and other important plasma characteristics were achieved. Described are the operational space and plasma stability limits in the OH regime. The factors limiting operational space (MHD instabilities, runaway electrons, etc.) are discussed. New experiments on plasma fuelling are described. First results of experiments with a coaxial plasma gun injector are presented. Initial results of a plasma - wall interaction study are outlined. First results obtained with new diagnostic tools installed on the tokamak are presented. An auxiliary heating system test was performed. Preliminary results of simulations and experiments are given. (author)

  4. Globus Sensation Due to a Mobile Foreign Body in a 41-year-old Female

    Directory of Open Access Journals (Sweden)

    Saman Vegari

    2012-02-01

    Full Text Available Leech infestation could be associated with wide range of complications including epistax-is, stridor, hemoptysis, globus sensation, hematemesis, and vaginal bleeding. In the present case report. , we introduce a case of leech infestation in a 41-year-old female presenting with chronic globus sensation, stridor, vomiting and dysphagia later diagnosed with leech infestation. Therefore, leech bites might be considered as a differential. Diagnosis of glo-bus sensation in the endemic rural areas where in unhealthy water from natural sources is consumed without taking required hygienic precautions.

  5. Characterization of Thermophilic Halotolerant Aeribacillus pallidus TD1 from Tao Dam Hot Spring, Thailand

    Directory of Open Access Journals (Sweden)

    Somchai Santiwatanakul

    2011-08-01

    Full Text Available The bacterial strain TD1 was isolated from Tao Dam hot spring in Thailand. Strain TD1 was Gram positive, rod-shaped, aerobic, motile, and endospore forming. The cell was 2.0–40 mm in length and about 0.4 mm in diameter. The optimum growth occurred at 55–60 °C and at pH 7–8. Strain TD1 was able to grow on medium containing up to 10% NaCl. The DNA G+C content was 38.9 mol%. The cellular fatty acid content was mainly C16:0, which comprised 25.04% of the total amount of cellular fatty acid. 16S rDNA showed 99% identity to Aeribacillus pallidus DSM 3670T. Bayesian tree analysis strongly supported the idea that strain TD1 is affiliated with genus Aeribacillus, as Aeribacillus pallidus strain TD1. Although the 16S rDNA of A. pallidus strain TD1 is similar to that of A. pallidus DSM 3670T, some physiological properties and the cellular fatty acid profiles differ significantly. A. pallidus strain TD1 can produce extracellular pectate lyase, which has not been reported elsewhere for other bacterial strains in the genus Aeribacillus. A. pallidus strain TD1 may be a good candidate as a pectate lyase producer, which may have useful industrial applications.

  6. Characterization of thermophilic halotolerant Aeribacillus pallidus TD1 from Tao Dam Hot Spring, Thailand.

    Science.gov (United States)

    Yasawong, Montri; Areekit, Supatra; Pakpitchareon, Arda; Santiwatanakul, Somchai; Chansiri, Kosum

    2011-01-01

    The bacterial strain TD1 was isolated from Tao Dam hot spring in Thailand. Strain TD1 was Gram positive, rod-shaped, aerobic, motile, and endospore forming. The cell was 2.0-40 μm in length and about 0.4 μm in diameter. The optimum growth occurred at 55-60 °C and at pH 7-8. Strain TD1 was able to grow on medium containing up to 10% NaCl. The DNA G+C content was 38.9 mol%. The cellular fatty acid content was mainly C(16:0), which comprised 25.04% of the total amount of cellular fatty acid. 16S rDNA showed 99% identity to Aeribacillus pallidus DSM 3670(T). Bayesian tree analysis strongly supported the idea that strain TD1 is affiliated with genus Aeribacillus, as Aeribacillus pallidus strain TD1. Although the 16S rDNA of A. pallidus strain TD1 is similar to that of A. pallidus DSM 3670(T), some physiological properties and the cellular fatty acid profiles differ significantly. A. pallidus strain TD1 can produce extracellular pectate lyase, which has not been reported elsewhere for other bacterial strains in the genus Aeribacillus. A. pallidus strain TD1 may be a good candidate as a pectate lyase producer, which may have useful industrial applications.

  7. [Compartmentalized organization of human corpus striatum].

    Science.gov (United States)

    Prensa, L; Parent, A; Giménez-Amaya, J M

    The compartmentalization of the human striatum was first established thanks to the pioneer work of Graybiel and Ragsdale in 1978. These authors described in the human striatum, as well as in the cats and primates, zones poorly stained for the enzyme acetylcholinesterase, which they termed striosomes, that lie in more intensely stained matrix. The striosome/matrix subdivision of the striatum is supported by the distribution of a wide variety of transmitter-related substances and by the organization of striatal afferent and efferent connections. The results of many studies performed in different species in the last twenty years have indicated that the chemical heterogeneity of striatum is more complex than the simple subdivision into striosomes and matrix compartments. Thus, a further subdivisions of the dual striosome/matrix system has been proposed on the basis of the results of a huge amount of works combining tract tracing methods with histochemical techniques. The matrix has been demonstrated to be heterogeneous by containing numerous functional modules that were termed matrisomes. Furthermore, the most recent study of the distribution of a wide variety of neurochemical markers in the striosomal compartment of the human striatum, has revealed that the striosomes are themselves heterogeneous, being composed of a central core and a peripheral region. Since it is now twenty years from the first description of the striosome/matrix organization of the striatum, in this review we intend to summarize the major finding regarding the compartmental organization of this subcortical structure that have been obtained during this period of time.

  8. Enlargement of thalamic nuclei in Tourette syndrome

    DEFF Research Database (Denmark)

    Miller, Ann M; Bansal, Ravi; Hao, Xuejun

    2010-01-01

    : Morphological abnormalities in the thalamus, together with the disturbances reported in the sensorimotor cortex, striatum, and globus pallidus, support the hypothesis of a circuitwide disorder within motor pathways in TS. The connectivity and function of the numerous and diverse thalamic nuclei within cortical...... in motor circuits to attenuate the severity of tics....

  9. GeoDataspaces: Simplifying Data Management Tasks with Globus

    Science.gov (United States)

    Malik, T.; Chard, K.; Tchoua, R. B.; Foster, I.

    2014-12-01

    Data and its management are central to modern scientific enterprise. Typically, geoscientists rely on observations and model output data from several disparate sources (file systems, RDBMS, spreadsheets, remote data sources). Integrated data management solutions that provide intuitive semantics and uniform interfaces, irrespective of the kind of data source are, however, lacking. Consequently, geoscientists are left to conduct low-level and time-consuming data management tasks, individually, and repeatedly for discovering each data source, often resulting in errors in handling. In this talk we will describe how the EarthCube GeoDataspace project is improving this situation for seismologists, hydrologists, and space scientists by simplifying some of the existing data management tasks that arise when developing computational models. We will demonstrate a GeoDataspace, bootstrapped with "geounits", which are self-contained metadata packages that provide complete description of all data elements associated with a model run, including input/output and parameter files, model executable and any associated libraries. Geounits link raw and derived data as well as associating provenance information describing how data was derived. We will discuss challenges in establishing geounits and describe machine learning and human annotation approaches that can be used for extracting and associating ad hoc and unstructured scientific metadata hidden in binary formats with data resources and models. We will show how geounits can improve search and discoverability of data associated with model runs. To support this model, we will describe efforts related towards creating a scalable metadata catalog that helps to maintain, search and discover geounits within the Globus network of accessible endpoints. This talk will focus on the issue of creating comprehensive personal inventories of data assets for computational geoscientists, and describe a publishing mechanism, which can be used to

  10. Association between swallow perception and esophageal bolus clearance in patients with globus sensation.

    Science.gov (United States)

    Chen, Chien-Lin; Yi, Chih-Hsun; Liu, Tso-Tsai

    2013-04-01

    Globus sensation is common, but its pathogenesis is not yet clear. Our purpose was to investigate subjective perception of swallowing and esophageal motility by combined multichannel intraluminal impedance and manometry (MII-EM) for patients with globus sensation. Combined MII-EM was performed for 25 globus patients and 15 healthy controls. Swallows were abnormal if hypocontractivity or simultaneous contractions occurred. Esophageal bolus transit was incomplete if bolus exit was not found at one or more of all measurement sites. Perception of each swallow was assessed by use of a standardized scoring system, and was enhanced if the score was >1. Few globus patients reported enhanced perception during viscous or solid swallows. Incomplete bolus transit and enhanced perception occurred similarly between viscous and solid boluses. Agreement between enhanced perception and proximal bolus clearance was greater during solid swallows (κ = 0.45, 95 % CI: 0.32-0.58) than during viscous swallows (κ = 0.13, 95 % CI: 0-0.25) (P perception and total bolus clearance was greater during solid swallows (κ = 0.46, 95 % CI: 0.34-0.58) than during viscous swallows (κ = 0.11, 95 % CI: 0-0.22) (P perception is uncommon in patients with globus sensation, although there is a significant association between enhanced esophageal perception and solid bolus clearance. Application of a solid bolus may help better delineation of the interrelationship between the subjective perception of bolus passage and the objective measurement of bolus clearance.

  11. Globus Nexus: A Platform-as-a-Service provider of research identity, profile, and group management

    Energy Technology Data Exchange (ETDEWEB)

    Chard, Kyle; Lidman, Mattias; McCollam, Brendan; Bryan, Josh; Ananthakrishnan, Rachana; Tuecke, Steven; Foster, Ian

    2016-03-01

    Globus Nexus is a professionally hosted Platform-as-a-Service that provides identity, profile and group management functionality for the research community. Many collaborative e-Science applications need to manage large numbers of user identities, profiles, and groups. However, developing and maintaining such capabilities is often challenging given the complexity of modern security protocols and requirements for scalable, robust, and highly available implementations. By outsourcing this functionality to Globus Nexus, developers can leverage best-practice implementations without incurring development and operations overhead. Users benefit from enhanced capabilities such as identity federation, flexible profile management, and user-oriented group management. In this paper we present Globus Nexus, describe its capabilities and architecture, summarize how several e-Science applications leverage these capabilities, and present results that characterize its scalability, reliability, and availability.

  12. [Isolation and partial structural characteristics of major toxic components of Latrodectus pallidus venom].

    Science.gov (United States)

    Charakha, A R; Shevchenko, L V; Molodkin, A K; Pluzhnikov, K A; Volkova, T M; Grishin, E V

    1997-03-01

    Toxic components of the Latrodectus pallidus spider venom were isolated and characterized. The venom was shown to contain a toxin specific for mammals and at least one insectospecific toxin. Partial amino acid sequences of both toxins were determined, and their high structural homology with previously studied alpha-latrotoxin and alpha-latroinsectotoxin from L. mactans tredecimguttatus was found.

  13. More than Just Fun and Games: BSG and Glo-Bus as Strategic Education Instruments

    Science.gov (United States)

    Karriker, Joy H.; Aaron, Joshua R.

    2014-01-01

    Simulations like the BSG and Glo-Bus allow students the opportunity to practice their integrated, strategic management skills in a relatively risk-free environment or "live case." We review these games and address their strengths, along with the challenges associated with their classroom application. Because of their sound designs and…

  14. Pathophysiology and treatment of patients with globus sensation ―from the viewpoint of esophageal motility dysfunction―

    Science.gov (United States)

    Manabe, Noriaki; Tsutsui, Hideaki; Kusunoki, Hiroaki; Hata, Jiro; Haruma, Ken

    2014-01-01

    "Globus sensation" is often described as the sensation of a lump in the throat associated with dry swallowing or the need for dry swallowing, which disappears completely during eating or drinking and for which no organic cause can be established. Due to the uncertain etiology of "globus sensation", it remains difficult to establish standard treatment strategies for affected patients. Lately most attention has been focused on gastroesophageal reflux disease and several reports have indicated that there is a close relationship between esophageal acid reflux and globus sensation. Nowadays, empirical therapy with a high dose of a proton pump inhibitor (PPI) is considered to be indicated for patients with globus sensation, after excluding organic diseases such as pharyngeal cancer, Zenker's diverticulum, or thyroid enlargement. If patients are nonresponsive to PPI therapy, evaluation of esophageal motility should be done. In our recent study, 47.9% had abnormal esophageal motility, with the most common esophageal motility abnormality being an ineffective esophageal motility in PPI-resistant patients with globus sensation. This suggests that prokinetics alone or adding prokinetics to PPI should be the treatment to be considered, although few studies have investigated the efficacy of prokinetics in the treatment of patients with globus sensation. If patients without any esophageal motility dysfunctions are nonresponsive to PPI therapy, either cognitive-behavioral therapy, anti-depressants, or gabapentin could be helpful, although further well-designed, randomized controlled large-scale studies will be necessary to determine the effectiveness of each treatment strategy on patients with globus sensation. PMID:26081369

  15. Production and characterization of a new antibacterial peptide obtained from Aeribacillus pallidus SAT4

    OpenAIRE

    Muhammad, Syed Aun; Ahmed, Safia

    2015-01-01

    A novel thermophilic bacterial strain of the genus Aeribacillus was isolated from Thar Dessert Pakistan. This strain showed significant antibacterial activity against Micrococcus luteus, Staphylococcus aureus, and Pseudomonas aeruginosa. The strain coded as ‘SAT4’ resembled with Aeribacillus pallidus in the morphological, biochemical and molecular tests. The production of antibacterial metabolites by SAT4 was optimized. These active metabolites were precipitated by 50% ammonium sulphate and p...

  16. Structural and biochemical characterization of a nitrilase from the thermophilic bacterium, Geobacillus pallidus RAPc8.

    Science.gov (United States)

    Williamson, Dael S; Dent, Kyle C; Weber, Brandon W; Varsani, Arvind; Frederick, Joni; Thuku, Robert N; Cameron, Rory A; van Heerden, Johan H; Cowan, Donald A; Sewell, B Trevor

    2010-09-01

    Geobacillus pallidus RAPc8 (NRRL: B-59396) is a moderately thermophilic gram-positive bacterium, originally isolated from Australian lake sediment. The G. pallidus RAPc8 gene encoding an inducible nitrilase was located and cloned using degenerate primers coding for well-conserved nitrilase sequences, coupled with inverse PCR. The nitrilase open reading frame was cloned into an expression plasmid and the expressed recombinant enzyme purified and characterized. The protein had a monomer molecular weight of 35,790 Da, and the purified functional enzyme had an apparent molecular weight of approximately 600 kDa by size exclusion chromatography. Similar to several plant nitrilases and some bacterial nitrilases, the recombinant G. pallidus RAPc8 enzyme produced both acid and amide products from nitrile substrates. The ratios of acid to amide produced from the substrates we tested are significantly different to those reported for other enzymes, and this has implications for our understanding of the mechanism of the nitrilases which may assist with rational design of these enzymes. Electron microscopy and image classification showed complexes having crescent-like, "c-shaped", circular and "figure-8" shapes. Protein models suggested that the various complexes were composed of 6, 8, 10 and 20 subunits, respectively.

  17. Characterization and emulsifying property of a novel bioemulsifier by Aeribacillus pallidus YM-1.

    Science.gov (United States)

    Zheng, C; Li, Z; Su, J; Zhang, R; Liu, C; Zhao, M

    2012-07-01

      Biosurfactants and bioemulsifiers commonly have the advantages of biodegradability, low toxicity, selectivity and biocompatibility over chemically synthesized surfactants. The goal of the study is to present a novel bioemulsifier with great application potential.   Aeribacillus pallidus YM-1, isolated from crude oil contaminated soil, was found to produce a novel high molecular bioemulsifier with an emulsification index of 60 ± 1% without remarkable surface tension reduction (45·7 ± 0·1 mN m(-1) ). The number-average molecular weight was determined as 526 369 Da by gel permeation chromatography analysis. Bioemulsifier was subjected to FT-IR and a complex of carbohydrates (41·1%), lipids (47·6%) and proteins (11·3%) was determined.   The bioemulsifier of A. pallidus YM-1 was isolated from the glucose-based culture medium and characterized with the help of chemical analytical techniques. The bioemulsifier exhibited a promising emulsifying property for biotechnology application potential in bioremediation and microbial enhanced oil recovery.   This is the first report of the bioemulsifier production by A. pallidus. The potential emulsifying activity of the bioemulsifier in the present study may be explored in various biotechnological and industrial applications. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  18. Biofilm characteristics and evaluation of the sanitation procedures of thermophilic Aeribacillus pallidus E334 biofilms.

    Science.gov (United States)

    Kilic, Tugba; Karaca, Basar; Ozel, Beste Piril; Ozcan, Birgul; Cokmus, Cumhur; Coleri Cihan, Arzu

    2017-04-01

    The ability of Aeribacillus pallidus E334 to produce pellicle and form a biofilm was studied. Optimal biofilm formation occurred at 60 °C, pH 7.5 and 1.5% NaCl. Extra polymeric substances (EPS) were composed of proteins and eDNA (21.4 kb). E334 formed biofilm on many surfaces, but mostly preferred polypropylene and glass. Using CLSM analysis, the network-like structure of the EPS was observed. The A. pallidus biofilm had a novel eDNA content. DNaseI susceptibility (86.8% removal) of eDNA revealed its importance in mature biofilms, but the purified eDNA was resistant to DNaseI, probably due to its extended folding outside the matrix. Among 15 cleaning agents, biofilms could be removed with alkaline protease and sodium dodecyl sulphate (SDS). The removal of cells from polypropylene and biomass on glass was achieved with combined SDS/alkaline protease treatment. Strong A. pallidus biofilms could cause risks for industrial processes and abiotic surfaces must be taken into consideration in terms of sanitation procedures.

  19. A prospective cohort-study of 122 adult patients presenting to an otolaryngologist's office with globus pharyngeus

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; Schnack, Didde Traerup; Ravn, Andreas Tomaas

    2018-01-01

    OBJECTIVES: To investigate the epidemiology of globus pharyngeus in adult patients presenting to the otolaryngologist's office. Also the predictors of persisting symptoms, prevalence of anxiety and the effect of clinical assessment were analyzed. DESIGN: This was a prospective cohort study. Follow......-up was done using a postal questionnaire. SETTING: One otolaryngologists' office comprising three medical doctors. PARTICIPANTS: 122 consecutive globus patients presenting to one otolaryngology office in a one-year period. MAIN OUTCOME MEASURES: Globus incidence, gender- and age-distribution, predictors...... of persisting symptoms and the patient's health related concerns. RESULTS: 3.8% of first-time visits were regarding globus. The mean age was 48 years [range 20-88 y] and a female predominance was found (ratio 1.49). 84% experienced anxiety, mainly due to fear of cancer. The most common pathological findings...

  20. Using Globus GridFTP to Transfer and Share Big Data | Poster

    Science.gov (United States)

    By Ashley DeVine, Staff Writer, and Mark Wance, Guest Writer; photo by Richard Frederickson, Staff Photographer Transferring big data, such as the genomics data delivered to customers from the Center for Cancer Research Sequencing Facility (CCR SF), has been difficult in the past because the transfer systems have not kept pace with the size of the data. However, the situation is changing as a result of the Globus GridFTP project.

  1. Plasma jet source parameter optimisation and experiments on injection into Globus-M spherical tokamak

    International Nuclear Information System (INIS)

    Gusev, V.K.; Petrov, Yu.V.; Sakharov, N.V.; Semenov, A.A.; Voronin, A.V.

    2005-01-01

    Results of theoretical and experimental research on the plasma sources and injection of plasma and gas jet produced by the modified source into tokamak Globus-M are presented. An experimental test stand was developed for investigation of intense plasma jet generation. Optimisation of pulsed coaxial accelerator parameters by means of analytical calculations is performed with the aim of achieving the highest flow velocity at limited coaxial electrode length and discharge current. The optimal parameters of power supply to generate a plasma jet with minimal impurity contamination and maximum flow velocity were determined. A comparison of experimental and calculation results is made. Plasma jet parameters are measured, such as: impurity species content, pressure distribution across the jet, flow velocity, plasma density, etc. Experiments on the interaction of a higher kinetic energy plasma jet with the magnetic field and plasma of the Globus-M tokamak were performed. Experimental results on plasma and gas jet injection into different Globus-M discharge phases are presented and discussed. Results are presented on the investigation of plasma jet injection as the source for discharge breakdown, plasma current startup and initial density rise. (author)

  2. Integration of Globus Online with the ATLAS PanDA Workload Management System

    International Nuclear Information System (INIS)

    Contreras, C; Deng, W; Maeno, T; Potekhin, M; Nilsson, P

    2012-01-01

    The PanDA Workload Management System is the basis for distributed production and analysis for the ATLAS experiment at the LHC. In this role, it relies on sophisticated dynamic data movement facilities developed in ATLAS. In certain scenarios, such as small research teams in ATLAS Tier-3 sites and non-ATLAS Virtual Organizations, the overhead of installation and operation of these components makes their use not very cost effective. Globus Online is an emerging new tool from the Globus Alliance, which already proved popular within the research community. It provides the users with fast and robust file transfer capabilities that can also be managed from a Web interface, and in addition to grid sites, can have individual workstations and laptops serving as data transmission endpoints. We will describe the integration of the Globus Online functionality into the PanDA suite of software, in order to give more flexibility in choosing the method of data transfer to ATLAS Tier-3 and Open Science Grid (OSG) users.

  3. Role of transnasal flexible laryngo-oesophagoscopy (TNFLO) in investigating patients with globus symptoms.

    Science.gov (United States)

    Mohammed, H; Coates, M; Masterson, L; Chan, W Y; Hassan, Y; Nassif, R

    2017-12-01

    To explore the rationale for investigating patients presenting with globus symptoms. In this regard, we also assess the efficacy and safety of transnasal flexible laryngo-oesophagoscopy (TNFLO). A prospective study in a head and neck cancer centre of patients with persistent globus symptoms with normal flexible nasoendoscopy/indirect mirror laryngoscopy and failure of first-line medical treatment. The role of TNFLO in investigating these patients was assessed. A total of 218 patients were recruited in this study. Positive findings included upper aerodigestive cancers in two patients, other pathologies included reflux (four patients), cricopharyngeus-related pathologies (19 patients), candida (five patients). There were only five re-referrals of patients who were discharged following normal examination with TNFLO. In nine patients, TNFLO could not be completed and they went on to have other diagnostic procedures CONCLUSION: This article is the largest to date in the UK to assess the role of TNFLO in investigating patients with globus symptoms. TNFLO is equal to rigid endoscopy as a diagnostic tool. However, it is superior in terms of image clarity, ability to record video images and safety. © 2017 John Wiley & Sons Ltd.

  4. Encoding by synchronization in the primate striatum.

    Science.gov (United States)

    Adler, Avital; Finkes, Inna; Katabi, Shiran; Prut, Yifat; Bergman, Hagai

    2013-03-13

    Information is encoded in the nervous system through the discharge and synchronization of single neurons. The striatum, the input stage of the basal ganglia, is divided into three territories: the putamen, the caudate, and the ventral striatum, all of which converge onto the same motor pathway. This parallel organization suggests that there are multiple and competing systems in the basal ganglia network controlling behavior. To explore which mechanism(s) enables the different striatal domains to encode behavioral events and to control behavior, we compared the neural activity of phasically active neurons [medium spiny neurons (MSNs), presumed projection neurons] and tonically active neurons (presumed cholinergic interneurons) across striatal territories from monkeys during the performance of a well practiced task. Although neurons in all striatal territories displayed similar spontaneous discharge properties and similar temporal modulations of their discharge rates to the behavioral events, their correlation structure was profoundly different. The distributions of signal and noise correlation of pairs of putamen MSNs were strongly shifted toward positive correlations and these two measures were correlated. In contrast, MSN pairs in the caudate and ventral striatum displayed symmetrical, near-zero signal and noise correlation distributions. Furthermore, only putamen MSN pairs displayed different noise correlation dynamics to rewarding versus neutral/aversive cues. Similarly, the noise correlation between tonically active neuron pairs was stronger in the putamen than in the caudate. We suggest that the level of synchronization of the neuronal activity and its temporal dynamics differentiate the striatal territories and may thus account for the different roles that striatal domains play in behavioral control.

  5. Urethritis due to corynebacterium striatum: An emerging germ.

    Science.gov (United States)

    Frikh, Mohammed; El Yaagoubi, Imad; Lemnouer, Abdelhay; Elouennass, Mostafa

    2015-01-01

    Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is part of mucous and skin flora. It has been considered as a causative agent of many infections in intensive care, neurology, traumatology and urology, but was never implicated in non-gonococcal urethritis. We report the case of a nosocomial urethritis due to Corynebacterium striatum following resection of an intrameatus condyloma.

  6. Production and properties of two novel exopolysaccharides synthesized by a thermophilic bacterium Aeribacillus pallidus 418.

    Science.gov (United States)

    Radchenkova, Nadja; Vassilev, Spasen; Panchev, Ivan; Anzelmo, Gianluca; Tomova, Iva; Nicolaus, Barbara; Kuncheva, Margarita; Petrov, Kaloyan; Kambourova, Margarita

    2013-09-01

    Synthesis of innovative exocellular polysaccharides (EPSs) was reported for few thermophilic microorganisms as one of the mechanisms for surviving at high temperature. Thermophilic aerobic spore-forming bacteria able to produce exopolysaccharides were isolated from hydrothermal springs in Bulgaria. They were referred to four species, such as Aeribacillus pallidus, Geobacillus toebii, Brevibacillus thermoruber, and Anoxybacillus kestanbolensis. The highest production was established for the strain 418, whose phylogenetic and phenotypic properties referred it to the species A. pallidus. Maltose and NH4Cl were observed to be correspondingly the best carbon and nitrogen sources and production yield was increased more than twofold in the process of culture condition optimization. After purification of the polymer fraction, a presence of two different EPSs, electroneutral EPS 1 and negatively charged EPS 2, in a relative weight ratio 3:2.2 was established. They were heteropolysaccharides consisting of unusual high variety of sugars (six for EPS 1 and seven for EPS 2). Six of the sugars were common for both EPSs. The main sugar in EPS 1 was mannose (69.3 %); smaller quantities of glucose (11.2 %), galactosamine (6.3 %), glucosamine (5.4 %), galactose (4.7 %), and ribose (2.9 %) were also identified. The main sugar in EPS 2 was also mannose (33.9 %), followed by galactose (17.9 %), glucose (15.5 %), galactosamine (11.7 %), glucosamine (8.1 %), ribose (5.3 %), and arabinose (4.9 %). Both polymers showed high molecular weight and high thermostability.

  7. Striatum on the anxiety map: Small detours into adolescence.

    Science.gov (United States)

    Lago, Tiffany; Davis, Andrew; Grillon, Christian; Ernst, Monique

    2017-01-01

    Adolescence is the most sensitive period for the development of pathological anxiety. Moreover, specific neural changes associated with the striatum might be related to adolescent vulnerability to anxiety. Up to now, the study of anxiety has primarily focused on the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus and ventromedial prefrontal cortex (vmPFC), while the striatum has typically not been considered as part of the anxiety system. This review proposes the addition of the striatum, a complex, multi-component structure, to the anxiety network by underscoring two lines of research. First, the co-occurrence of the adolescent striatal development with the peak vulnerability of adolescents to anxiety disorders might potentially reflect a causal relationship. Second, the recognition of the role of the striatum in fundamental behavioral processes that do affect anxiety supports the putative importance of the striatum in anxiety. These behavioral processes include (1) attention, (2) conditioning/prediction error, and (3) motivation. This review proposes a simplistic schematic representation of the anxiety circuitry that includes the striatum, and aims to promote further work in this direction, as the role of the striatum in shaping an anxiety phenotype during adolescence could have critical implications for understanding and preventing the peak onset of anxiety disorders during this period. This article is part of a Special Issue entitled SI: Adolescent plasticity. Published by Elsevier B.V.

  8. Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux.

    Science.gov (United States)

    Tokashiki, Ryoji; Okamoto, Isaku; Funato, Nobutoshi; Suzuki, Mamoru

    2013-08-21

    To investigate the effect of rikkunshito on laryngopharyngeal reflux (LPR) symptoms and gastric emptying in patients with proton-pump inhibitor (PPI)-refractory LPR. In total, 22 patients with LPR were enrolled. Following a 2-wk treatment with PPI monotherapy, PPI-refractory LPR patients were randomly divided into two treatment groups (rikkunshito alone or rikkunshito plus the PPI, lansoprazole). LPR symptoms were assessed using a visual analog scale (VAS) score, gastrointestinal symptoms were assessed using the gastrointestinal symptom rating scale (GSRS), and gastric emptying was assessed using the radio-opaque marker method prior to and 4 wk following treatments. The 4-wk treatment with rikkunshito alone and with rikkunshito plus the PPI significantly decreased the globus sensation VAS scores. The VAS score for sore throat was significantly decreased following treatment with rikkunshito plus PPI but not by rikkunshito alone. Neither treatment significantly changed the GSRS scores. Rikkunshito improved delayed gastric emptying. We found a significant positive correlation between improvements in globus sensation and in gastric emptying (r² = 0.4582, P sensation in patients with PPI-refractory LPR, in part, because of stimulation of gastric emptying. Thus, rikkunshito is an effective treatment for PPI-refractory LPR.

  9. DNA-binding properties of the Bacillus subtilis and Aeribacillus pallidus AC6 σ(D) proteins.

    Science.gov (United States)

    Sevim, Elif; Gaballa, Ahmed; Beldüz, A Osman; Helmann, John D

    2011-01-01

    σ(D) proteins from Aeribacillus pallidus AC6 and Bacillus subtilis bound specifically, albeit weakly, to promoter DNA even in the absence of core RNA polymerase. Binding required a conserved CG motif within the -10 element, and this motif is known to be recognized by σ region 2.4 and critical for promoter activity.

  10. DNA-Binding Properties of the Bacillus subtilis and Aeribacillus pallidus AC6 σD Proteins▿

    Science.gov (United States)

    Sevim, Elif; Gaballa, Ahmed; Beldüz, A. Osman; Helmann, John D.

    2011-01-01

    σD proteins from Aeribacillus pallidus AC6 and Bacillus subtilis bound specifically, albeit weakly, to promoter DNA even in the absence of core RNA polymerase. Binding required a conserved CG motif within the −10 element, and this motif is known to be recognized by σ region 2.4 and critical for promoter activity. PMID:21097624

  11. Genome Sequence of Aeribacillus pallidus Strain GS3372, an Endospore-Forming Bacterium Isolated in a Deep Geothermal Reservoir

    OpenAIRE

    Sevasti Filippidou; Marion Jaussi; Thomas Junier; Tina Wunderlin; Nicole Jeanneret; Simona Regenspurg; Po-E Li; Chien-Chi Lo; Shannon Johnson; Kim McMurry; Cheryl D. Gleasner; Momchilo Vuyisich; Patrick S. Chain; Pilar Junier

    2015-01-01

    The genome of strain GS3372 is the first publicly available strain of Aeribacillus pallidus. This endospore-forming thermophilic strain was isolated from a deep geothermal reservoir. The availability of this genome can contribute to the clarification of the taxonomy of the closely related Anoxybacillus, Geobacillus, and Aeribacillus genera.

  12. DNA-Binding Properties of the Bacillus subtilis and Aeribacillus pallidus AC6 σD Proteins▿

    OpenAIRE

    Sevim, Elif; Gaballa, Ahmed; Beldüz, A. Osman; Helmann, John D.

    2010-01-01

    σD proteins from Aeribacillus pallidus AC6 and Bacillus subtilis bound specifically, albeit weakly, to promoter DNA even in the absence of core RNA polymerase. Binding required a conserved CG motif within the −10 element, and this motif is known to be recognized by σ region 2.4 and critical for promoter activity.

  13. Genome Sequence of Aeribacillus pallidus Strain GS3372, an Endospore-Forming Bacterium Isolated in a Deep Geothermal Reservoir.

    Science.gov (United States)

    Filippidou, Sevasti; Jaussi, Marion; Junier, Thomas; Wunderlin, Tina; Jeanneret, Nicole; Regenspurg, Simona; Li, Po-E; Lo, Chien-Chi; Johnson, Shannon; McMurry, Kim; Gleasner, Cheryl D; Vuyisich, Momchilo; Chain, Patrick S; Junier, Pilar

    2015-08-27

    The genome of strain GS3372 is the first publicly available strain of Aeribacillus pallidus. This endospore-forming thermophilic strain was isolated from a deep geothermal reservoir. The availability of this genome can contribute to the clarification of the taxonomy of the closely related Anoxybacillus, Geobacillus, and Aeribacillus genera. Copyright © 2015 Filippidou et al.

  14. Dopamine release in ventral striatum of pathological gamblers losing money

    DEFF Research Database (Denmark)

    Linnet, J; Peterson, E; Doudet, D J

    2010-01-01

    Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money. Objective: To investigate dopaminergic neurotransmission in relation to monetary reward and punishment in pathological gambling. Pathological gamblers (PG) often continue...... gambling despite losses, known as 'chasing one's losses'. We therefore hypothesized that losing money would be associated with increased dopamine release in the ventral striatum of PG compared with healthy controls (HC). Method: We used Positron Emission Tomography (PET) with [(11)C]raclopride to measure...... dopamine release in the ventral striatum of 16 PG and 15 HC playing the Iowa Gambling Task (IGT). Results: PG who lost money had significantly increased dopamine release in the left ventral striatum compared with HC. PG and HC who won money did not differ in dopamine release. Conclusion: Our findings...

  15. Native valve endocarditis caused by an organism resembling Corynebacterium striatum.

    OpenAIRE

    Markowitz, S M; Coudron, P E

    1990-01-01

    An organism resembling Corynebacterium striatum was isolated from the blood of a patient with acute aortic valvular insufficiency and no history of valvular heart disease. At autopsy, histopathologic examination of the aortic valve revealed pleomorphic gram-positive bacilli and destruction of valvular tissue. Our isolate differed from other nondiphtherial corynebacteria, including the type strain of C. striatum (ATCC 6940), in its ability to reduce nitrite. Nitrite reduction may be useful for...

  16. Diet, digestion, and food preferences of Galapagos land iguanas. [Conolophus pallidus

    Energy Technology Data Exchange (ETDEWEB)

    Christian, K.A.; Tracy, C.R.; Porter, W.P.

    1984-01-01

    The choice of food types and the length of time food passed through the gastrointestinal tract were determined in free-ranging Conolophus pallidus on Isla Santa Fe, Galapogos throughout the year. Natural foods were analyzed for energy, percent cellulose, percent nitrogen, and calcium as indices of the quality of food. Foods of highest quality were found to be among the preferred foods, but not all preferred foods were of high quality with respect to the nutrients measured. Passage time of food through the gastrointestinal tract, digestive efficiency, and digestion of cellulose were determined on captive Conolophus subcristatus. Ability to digest cellulose and digestive efficiency varied among five caged iguanas. Intra- and interspecific variabilities in digestive capacities result from variability in ecological factors, and interspecific variability among iguanines probably reflects differences in colic anatomy and the ability to absorb nutrients from the hindgut. 23 references, 4 tables.

  17. Functional connectivity of the dorsal striatum in female musicians

    Directory of Open Access Journals (Sweden)

    Shoji eTanaka

    2016-04-01

    Full Text Available The dorsal striatum (caudate/putamen is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians.Resting state functional magnetic resonance imaging (fMRI data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to graph theoretical analysis and functional connectivity analysis. The graph theoretical analysis of the entire brain revealed that the degree, which represents the number of connections, of the bilateral putamen was significantly lower in musicians than in nonmusicians. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum and between the left caudate nucleus and cerebellum. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum, with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers. To the best of our knowledge, this is the first study suggesting that long-term musical training results in a less extensive or selective functional network of the dorsal striatum.

  18. Functional Connectivity of the Dorsal Striatum in Female Musicians.

    Science.gov (United States)

    Tanaka, Shoji; Kirino, Eiji

    2016-01-01

    The dorsal striatum (caudate/putamen) is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC) motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians. Resting state functional magnetic resonance imaging (fMRI) data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to functional connectivity analysis and graph theoretical analysis. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum (FO) and between the left caudate nucleus and cerebellum. The graph theoretical analysis of the entire brain revealed that the degrees, which represent the numbers of connections, of the bilateral putamen were significantly lower in musicians than in nonmusicians. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers, suggesting that long-term musical training reshapes the functional network of the dorsal striatum to be less extensive or selective.

  19. Reconstruction of equilibrium magnetic configurations in the Globus-M spherical tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Sakharov, N. V., E-mail: nikolay.sakharov@mail.ioffe.ru; Voronin, A. V.; Gusev, V. K. [Russian Academy of Sciences, Ioffe Physical Technical Institute (Russian Federation); Kavin, A. A.; Kamenshchikov, S. N.; Lobanov, K. M. [Efremov Research Institute of Electrophysical Apparatus (Russian Federation); Minaev, V. B.; Novokhatsky, A. N.; Patrov, M. I., E-mail: michael.patrov@mail.ioffe.ru; Petrov, Yu. V.; Shchegolev, P. B. [Russian Academy of Sciences, Ioffe Physical Technical Institute (Russian Federation)

    2015-12-15

    The results of reconstruction of equilibrium magnetic configurations in the Globus-M spherical tokamak by means of the EFIT code and by the method of movable filaments with the use of the data from magnetic measurements are compared. The EFIT code allows one to completely reconstruct the magnetic configuration by solving the Grad−Shafranov equation. In the method of movable filaments, the distribution of the toroidal current flowing through the plasma is described by a set of infinitely thin current-carrying rings. In this method, the last closed magnetic surface (LCMS) and the open surfaces lying beyond the LCMS are calculated. Using both methods, the coordinates of the regions where the separatrix strikes the divertor plates were determined. The results obtained agree well with the distributions of the temperature over the tungsten divertor tiles measured using an IR camera.

  20. Cholinergic interneurons are differentially distributed in the human striatum.

    Science.gov (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2007-11-14

    The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. This study was carried out using stereological methods to examine the volume and density (cells/mm(3)) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a special integration of information by interneurons

  1. Envenomation by neotropical Opisthoglyphous colubrid Thamnodynastes cf. pallidus Linné, 1758 (Serpentes:Colubridae in Venezuela Envenenamiento por la colubrida opistoglifa Thamnodynastes cf. pallidus Linné, 1758 (Serpentes:Colubridae en Venezuela

    Directory of Open Access Journals (Sweden)

    Fresnel Diaz

    2004-10-01

    Full Text Available This is a case report of a "non-venomous" snake bite in a herpetologist observed at the Sciences Faculty of the Universidad de los Andes (Mérida, Venezuela. The patient was bitten on the middle finger of the left hand, and shows signs of pronounced local manifestations of envenomation such as bleeding from the tooth imprint, swelling and warmth. He was treated with local care, analgesics, and steroids. He was dismissed from the hospital and observed at home during five days with marked improvement of envenomation. The snake was brought to the medical consult and identified as a Thamnodynastes cf. pallidus specimen. This report represents the first T. pallidus accident described in a human.Se reporta un caso de una mordedura de serpiente "no venenosa", en un herpetólogo observado en la Facultad de Ciencias de la Universidad de los Andes (Mérida, Venezuela. El paciente fue mordido en el dedo medio de la mano izquierda, mostrando pronunciados signos locales de sangramiento por la impronta ocasionada por los dientes de la serpiente, edema y calor local. El paciente fue tratado con cuidados locales, analgésicos y esteroides. Fue dado de alta del hospital y observado en el hogar durante 5 días, con marcada mejoría del envenenamiento. La serpiente fue traída a la consulta médica e identificada como un espécimen de Thamnodynastes cf. pallidus. Este es el primer caso humano descrito, ocasionado por un T. pallidus.

  2. A multilevel approach to examining cephalopod growth using Octopus pallidus as a model.

    Science.gov (United States)

    Semmens, Jayson; Doubleday, Zoë; Hoyle, Kate; Pecl, Gretta

    2011-08-15

    Many aspects of octopus growth dynamics are poorly understood, particularly in relation to sub-adult or adult growth, muscle fibre dynamics and repro-somatic investment. The growth of 5 month old Octopus pallidus cultured in the laboratory was investigated under three temperature regimes over a 12 week period: seasonally increasing temperatures (14-18°C); seasonally decreasing temperatures (18-14°C); and a constant temperature mid-way between seasonal peaks (16°C). Differences in somatic growth at the whole-animal level, muscle tissue structure and rate of gonad development were investigated. Continuous exponential growth was observed, both at a group and at an individual level, and there was no detectable effect of temperature on whole-animal growth rate. Juvenile growth rate (from 1 to 156 days) was also monitored prior to the controlled experiment; exponential growth was observed, but at a significantly faster rate than in the older experimental animals, suggesting that O. pallidus exhibit a double-exponential two-phase growth pattern. There was considerable variability in size-at-age even between individuals growing under identical thermal regimes. Animals exposed to seasonally decreasing temperatures exhibited a higher rate of gonad development compared with animals exposed to increasing temperatures; however, this did not coincide with a detectable decline in somatic growth rate or mantle condition. The ongoing production of new mitochondria-poor and mitochondria-rich muscle fibres (hyperplasia) was observed, indicated by a decreased or stable mean muscle fibre diameter concurrent with an increase in whole-body size. Animals from both seasonal temperature regimes demonstrated higher rates of new mitochondria-rich fibre generation relative to those from the constant temperature regime, but this difference was not reflected in a difference in growth rate at the whole-body level. This is the first study to record ongoing hyperplasia in the muscle tissue of an

  3. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  4. The dorsal striatum and ventral striatum play different roles in the programming of social behaviour: a tribute to Lex Cools.

    Science.gov (United States)

    van den Bos, Ruud

    2015-02-01

    Early work by Lex Cools suggested that the caudate nucleus (dorsal striatum) plays a role in programming social behaviour: enhanced activity in the caudate nucleus increased the extent to which ongoing behaviour is controlled by the individual's own behaviour (internal control) rather than by that of its partners (external control). Interestingly, later studies by others have indicated that the ventral striatum plays a role in external rather than internal control. Here, I discuss the role of these different striatal areas - and the emotional (ventral striatum) and cognitive control (dorsal striatum) system in which they are embedded - in the organization of social behaviour in the context of locus of control. Following on from this discussion, I will pay particular attention to individual differences in social behaviour (individuals with more internal or external control), focusing on the role of dopamine, serotonin and the effects of stress-related challenges in relation to their different position in a dominance hierarchy. I will subsequently allude to potential psychological and behavioural problems in the social domain following on from these differences in locus of control ['social obliviousness' (dorsal stratum) and 'social impulsivity' (ventral striatum)]. In doing so, I provide as a tribute a historical account of the early research by Lex Cools.

  5. Suitability of the alkalistable carbonic anhydrase from a polyextremophilic bacterium Aeribacillus pallidus TSHB1 in biomimetic carbon sequestration.

    Science.gov (United States)

    Bose, Himadri; Satyanarayana, T

    2016-10-01

    Carbonic anhydrase (CA) was produced from the polyextremophilic (halotolerant, moderately thermophilic and alkaliphilic) bacterium Aeribacillus pallidus TSHB1 isolated from water and sediment samples of Choti Anhoni hot spring of Pipariya, Madhya Pradesh (India), is being reported to be suitable for carbon sequestration. Growth and CA production were inhibited at higher CO2 concentration (5-10 %). Under optimized culture variables (tryptone 0.8 %, yeast extract 0.08 %, glucose 1 %, micronutrient solution 1 %, inoculums size 1.10 %, agitation 200 at pH 8, and temperature 55 °C), 3.7-fold higher CA production was attained than that under unoptimized conditions. The zymogram analysis of the partially purified CA revealed an activity band corresponding to 32 kDa. The enzyme is stable in the pH range between 8.0 and 11.0 with T 1/2 of 40, 15, and 8 min at 60, 70, and 80 °C, respectively. The CA of A. pallidus displayed a marked enhancement in the rate of CaCO3 precipitation from aqueous CO2. The CA-aided formation of CaCO3 was 42.5 mg mg(-1) protein. Scanning electron microscopy revealed the formation of rhomboid calcite crystals. This is the first report on the production and applicability of CA from the polyextremophilic A. pallidus in carbon sequestration.

  6. Recrystallized graphite utilization as the first wall material in Globus-M spherical tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Gusev, V.; Novokhatsky, A.N.; Petrov, Y.V.; Sakharov, N.V.; Terukov, E.I.; Trapeznikova, I.N. [A.F. IOFFE Physico-technical Institute, Russian Academy of Sciences, St Petersburg (Russian Federation); Denisov, E.A.; Kurdumov, A.A.; Kompaniec, T.N. [St. Petersburg State Univ., Research Institute of Physics (Russian Federation); Lebedev, V.M. [B.P. Konstantinov Nuclear Physics Institute, Russian Academy of Science, Gatchina (Russian Federation); Litunovstkii, N.V. [D.V. Efremov Institute of Electrophysical Apparatus, St.Petersburg (Russian Federation); Mazul, I. [Development of Plasma Facing Materials and Components Laboratory, EFREMOV INSTITUTE, St Petersbourg (Russian Federation)

    2007-07-01

    Full text of publication follows: Globus-M spherical tokamak, built at A.F. Ioffe Physico-Technical Institute in 1999 is the first Russian spherical tokamak and has the broad area of research in controlled fusion [1]. Besides small aspect ratio (A=1.5) the distinguishing feature of the tokamak is the powerful energy supply system and auxiliary heating, which give opportunity to reach high specific power deposition up to few W/cm{sup 3}. The utmost plasma current density and B/R ratio among spherical tokamaks allow operation in the range of high plasma densities {approx} 10{sup 20} m{sup -3}. This feature results in big power density loads to the first wall due to small plasma-wall spacing. The area of the first wall amour was gradually increased during few years since 2003, and nowadays reaches almost 90% of the inner vessel surface faced to plasma. Plasma facing protecting tiles are manufactured from recrystallized graphite doped by different elements (Ti, Si, B). Additionally the plasma facing surface was protected by films deposited during boronization. The tendency of short time and long time scale plasma parameters variation are discussed including the plasma performance improvement with increase of protected area. Technology of tiles preparation before installation into the tokamak vessel is briefly described, as well as technology of plasma facing armor preparation before the plasma experiments. Few protecting tiles doped by different elements which were exposed to plasma fluxes of dissimilar power densities for a long time were extracted from the vacuum vessel. The analysis of tiles material (RGT-91) to hold (accumulate) deuterium was made. The distribution of absorbed deuterium concentration along poloidal coordinate was measured. The elementary composition of the films deposited on the tiles was studied by Rutherford back scattering technique and by nuclear resonance reaction method. Other modern methods of surface and structural analysis of material

  7. Recrystallized graphite utilization as the first wall material in Globus-M spherical tokamak

    International Nuclear Information System (INIS)

    Gusev, V.; Novokhatsky, A.N.; Petrov, Y.V.; Sakharov, N.V.; Terukov, E.I.; Trapeznikova, I.N.; Denisov, E.A.; Kurdumov, A.A.; Kompaniec, T.N.; Lebedev, V.M.; Litunovstkii, N.V.; Mazul, I.

    2007-01-01

    Full text of publication follows: Globus-M spherical tokamak, built at A.F. Ioffe Physico-Technical Institute in 1999 is the first Russian spherical tokamak and has the broad area of research in controlled fusion [1]. Besides small aspect ratio (A=1.5) the distinguishing feature of the tokamak is the powerful energy supply system and auxiliary heating, which give opportunity to reach high specific power deposition up to few W/cm 3 . The utmost plasma current density and B/R ratio among spherical tokamaks allow operation in the range of high plasma densities ∼ 10 20 m -3 . This feature results in big power density loads to the first wall due to small plasma-wall spacing. The area of the first wall amour was gradually increased during few years since 2003, and nowadays reaches almost 90% of the inner vessel surface faced to plasma. Plasma facing protecting tiles are manufactured from recrystallized graphite doped by different elements (Ti, Si, B). Additionally the plasma facing surface was protected by films deposited during boronization. The tendency of short time and long time scale plasma parameters variation are discussed including the plasma performance improvement with increase of protected area. Technology of tiles preparation before installation into the tokamak vessel is briefly described, as well as technology of plasma facing armor preparation before the plasma experiments. Few protecting tiles doped by different elements which were exposed to plasma fluxes of dissimilar power densities for a long time were extracted from the vacuum vessel. The analysis of tiles material (RGT-91) to hold (accumulate) deuterium was made. The distribution of absorbed deuterium concentration along poloidal coordinate was measured. The elementary composition of the films deposited on the tiles was studied by Rutherford back scattering technique and by nuclear resonance reaction method. Other modern methods of surface and structural analysis of material exposed to prolonged

  8. A case study for cloud based high throughput analysis of NGS data using the globus genomics system

    Science.gov (United States)

    Bhuvaneshwar, Krithika; Sulakhe, Dinanath; Gauba, Robinder; Rodriguez, Alex; Madduri, Ravi; Dave, Utpal; Lacinski, Lukasz; Foster, Ian; Gusev, Yuriy; Madhavan, Subha

    2014-01-01

    Next generation sequencing (NGS) technologies produce massive amounts of data requiring a powerful computational infrastructure, high quality bioinformatics software, and skilled personnel to operate the tools. We present a case study of a practical solution to this data management and analysis challenge that simplifies terabyte scale data handling and provides advanced tools for NGS data analysis. These capabilities are implemented using the “Globus Genomics” system, which is an enhanced Galaxy workflow system made available as a service that offers users the capability to process and transfer data easily, reliably and quickly to address end-to-endNGS analysis requirements. The Globus Genomics system is built on Amazon 's cloud computing infrastructure. The system takes advantage of elastic scaling of compute resources to run multiple workflows in parallel and it also helps meet the scale-out analysis needs of modern translational genomics research. PMID:26925205

  9. A case study for cloud based high throughput analysis of NGS data using the globus genomics system

    Directory of Open Access Journals (Sweden)

    Krithika Bhuvaneshwar

    2015-01-01

    Full Text Available Next generation sequencing (NGS technologies produce massive amounts of data requiring a powerful computational infrastructure, high quality bioinformatics software, and skilled personnel to operate the tools. We present a case study of a practical solution to this data management and analysis challenge that simplifies terabyte scale data handling and provides advanced tools for NGS data analysis. These capabilities are implemented using the “Globus Genomics” system, which is an enhanced Galaxy workflow system made available as a service that offers users the capability to process and transfer data easily, reliably and quickly to address end-to-endNGS analysis requirements. The Globus Genomics system is built on Amazon's cloud computing infrastructure. The system takes advantage of elastic scaling of compute resources to run multiple workflows in parallel and it also helps meet the scale-out analysis needs of modern translational genomics research.

  10. Physiological and ecological consequences of sleeping-site selection by the Galapagos land iguana (Conolophus pallidus)

    Energy Technology Data Exchange (ETDEWEB)

    Christian, K.A.; Tracy, C.R.

    1984-01-01

    Field observations and biophysical models were combined to analyze sleeping-site selection by Galapagos land iguanas (Conolophus pallidus). Iguanas slept in different kinds of sleeping sites during different seasons. In the coolest season (garua), adult land iguanas were found in sleeping sites that were warmer than the coolest sites available. This may be because the garua season (cool, overcast, and foggy) is a time when environmental conditions mitigate against rapid warm-up in the mornings, so lizards may regulate nighttime body temperatures so that it is easier to warm up to preferred daytime body temperatures. In the warmest season, adult iguanas were found in the coolest sleeping sites available. This observation is consistent with hypotheses of voluntary hypothermia, which can be advantageous in energy conservation and in avoiding detrimental effects associated with maintenance of constant body temperatures throughout the day and night. Juvenile iguanas were found sleeping in rock crevices regardless of the ambient thermal environments. Such sites are likely to be important as refugia for this life stage, which, unlike the adult stage, is vulnerable to predation. It was concluded that selection of sleeping sites is a process that may help in avoidance of predation, optimization of body temperature at the end of the sleeping period, and reduction of metabolic costs during sleeping. The importance of some of these factors may change with the thermal milieu (e.g., season).

  11. Production and characterization of a new antibacterial peptide obtained from Aeribacillus pallidus SAT4

    Directory of Open Access Journals (Sweden)

    Syed Aun Muhammad

    2015-12-01

    Full Text Available A novel thermophilic bacterial strain of the genus Aeribacillus was isolated from Thar Dessert Pakistan. This strain showed significant antibacterial activity against Micrococcus luteus, Staphylococcus aureus, and Pseudomonas aeruginosa. The strain coded as ‘SAT4’ resembled with Aeribacillus pallidus in the morphological, biochemical and molecular tests. The production of antibacterial metabolites by SAT4 was optimized. These active metabolites were precipitated by 50% ammonium sulphate and purified through sephadex G-75 gel permeation chromatography and reverse phase HPLC. The molecular weight of 37 kDa was examined by SDS-PAGE. The structural elucidation of the purified product was studied by FTIR, 1H and 13C NMR. The X-ray diffractions study showed that the crystals belonged to the primitive orthorhombic lattice (a = 12.137, b = 13.421, c = 14.097 Å and 3D structure (proposed name: Aeritracin was determined. This new peptide antibacterial molecule can get a position in pharmaceutical and biotechnological industrial research.

  12. Production and characterization of a new antibacterial peptide obtained from Aeribacillus pallidus SAT4.

    Science.gov (United States)

    Muhammad, Syed Aun; Ahmed, Safia

    2015-12-01

    A novel thermophilic bacterial strain of the genus Aeribacillus was isolated from Thar Dessert Pakistan. This strain showed significant antibacterial activity against Micrococcus luteus , Staphylococcus aureus , and Pseudomonas aerugin osa. The strain coded as 'SAT4' resembled with Aeribacillus pallidus in the morphological, biochemical and molecular tests. The production of antibacterial metabolites by SAT4 was optimized. These active metabolites were precipitated by 50% ammonium sulphate and purified through sephadex G-75 gel permeation chromatography and reverse phase HPLC. The molecular weight of 37 kDa was examined by SDS-PAGE. The structural elucidation of the purified product was studied by FTIR, 1 H and 13 C NMR. The X-ray diffractions study showed that the crystals belonged to the primitive orthorhombic lattice ( a  = 12.137, b  = 13.421, c  = 14.097 Å) and 3D structure (proposed name: Aeritracin) was determined. This new peptide antibacterial molecule can get a position in pharmaceutical and biotechnological industrial research.

  13. Characterization of a novel protease from Aeribacillus pallidus strain VP3 with potential biotechnological interest.

    Science.gov (United States)

    Mechri, Sondes; Ben Elhoul Berrouina, Mouna; Omrane Benmrad, Maroua; Zaraî Jaouadi, Nadia; Rekik, Hatem; Moujehed, Emna; Chebbi, Alif; Sayadi, Sami; Chamkha, Mohamed; Bejar, Samir; Jaouadi, Bassem

    2017-01-01

    The present study investigates the purification and physico-chemical characterization of an extracellular protease from the Aeribacillus pallidus strain VP3 previously isolated from a geothermal oil-field (Sfax, Tunisia). The maximum protease activity recorded after 22h of incubation at 45°C was 3000U/ml. Pure enzyme, designated as SPVP, was obtained after ammonium sulfate fractionation (40-60%)-dialysis followed by heat-treatment (70°C for 30min) and UNO Q-6 FPLC anion-exchange chromatography. The purified enzyme is a monomer of molecular mass about 29kDa. The sequence of the 25 NH 2 -terminal residues of SPVP showed a high homology with those of Bacillus proteases. The almost complete inhibition by PMSF and DIFP confirmed that SPVP is a member of serine protease family. Its optima of pH and temperature were pH 10 and 60°C, respectively. Its half-life times at 70 and 80°C were 8 and 4h, respectively. Its catalytic efficiency was higher than those of SAPCG, Alcalase Ultra 2.5L, and Thermolysin type X. SPVP exhibited excellent stability to detergents and wash performance analysis revealed that it could remove blood-stains effectively and high resistance against organic solvents. These properties make SPVP a potential candidate for applications in detergent formulations and non-aqueous peptide biocatalysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Can two streams of auditory information be processed simultaneously? Evidence from the gleaning bat Antrozous pallidus.

    Science.gov (United States)

    Barber, J R; Razak, K A; Fuzessery, Z M

    2003-11-01

    A tenet of auditory scene analysis is that we can fully process only one stream of auditory information at a time. We tested this assumption in a gleaning bat, the pallid bat (Antrozous pallidus) because this bat uses echolocation for general orientation, and relies heavily on prey-generated sounds to detect and locate its prey. It may therefore encounter situations in which the echolocation and passive listening streams temporally overlap. Pallid bats were trained to a dual task in which they had to negotiate a wire array, using echolocation, and land on one of 15 speakers emitting a brief noise burst in order to obtain a food reward. They were forced to process both streams within a narrow 300 to 500 ms time window by having the noise burst triggered by the bats' initial echolocation pulses as it approached the wire array. Relative to single task controls, echolocation and passive sound localization performance was slightly, but significantly, degraded. The bats also increased echolocation interpulse intervals during the dual task, as though attempting to reduce temporal overlap between the signals. These results suggest that the bats, like humans, have difficulty in processing more than one stream of information at a time.

  15. The Role of the Modified Barium Swallow Study and Esophagram in Patients with Globus Sensation.

    Science.gov (United States)

    Dworkin, James P; Dowdall, Jayme R; Kubik, Mark; Thottam, Prasad John; Folbe, Adam

    2015-10-01

    Globus sensation (GS) is a common benign finding that is often associated with frequent throat clearing and is commonly a result of laryngopharyngeal reflux. The primary objective of this investigation was to examine the role of the modified barium swallow study (MBSS) with esophagram in the diagnosis and management patients who present with chief complaints of a GS. We hypothesize that these radiographic swallow studies do not add clinically significant information in the investigation of this common complaint. Retrospective chart review of patients with chief complaints of GS between 2000 and 2009 who underwent both MBSS and esophagram was conducted. Of the 380 patients who underwent MBSS, only 68 patients were eligible for this study. Over 70 % of patients were on reflux medicines, 81 % of the MBSS studies were normal, 62 % of the esophagram results were normal, 18 % of patients had a hiatal hernia, and 10 % exhibited signs of reflux. Esophagoscopy was performed in 45 % of patients, of which 35 % were normal. One patient initially had a normal esophagogastroduodenoscopy and then was subsequently diagnosed with gastric CA. Fifty-nine percent of patients underwent CT Neck with IV contrast, of which 67 % had minor findings. Positive findings are often benign and can be treated with reflux medications. Esophagoscopy was often normal and most sensitive only for hiatal hernia. No hypopharyngeal cancer was noted. Therefore, MBSS and esophagram for patients with GS are most often negative and fail to add significant diagnostic information.

  16. Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification

    Science.gov (United States)

    Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

    2011-01-01

    Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…

  17. Ebf1 controls early cell differentiation in the embryonic striatum.

    Science.gov (United States)

    Garel, S; Marín, F; Grosschedl, R; Charnay, P

    1999-12-01

    Ebf1/Olf-1 belongs to a small multigene family encoding closely related helix-loop-helix transcription factors, which have been proposed to play a role in neuronal differentiation. Here we show that Ebf1 controls cell differentiation in the murine embryonic striatum, where it is the only gene of the family to be expressed. Ebf1 targeted disruption affects postmitotic cells that leave the subventricular zone (SVZ) en route to the mantle: they appear to be unable to downregulate genes normally restricted to the SVZ or to activate some mantle-specific genes. These downstream genes encode a variety of regulatory proteins including transcription factors and proteins involved in retinoid signalling as well as adhesion/guidance molecules. These early defects in the SVZ/mantle transition are followed by an increase in cell death, a dramatic reduction in size of the postnatal striatum and defects in navigation and fasciculation of thalamocortical fibres travelling through the striatum. Our data therefore show that Ebf1 plays an essential role in the acquisition of mantle cell molecular identity in the developing striatum and provide information on the genetic hierarchies that govern neuronal differentiation in the ventral telencephalon.

  18. Attention modulates the dorsal striatum response to love stimuli.

    Science.gov (United States)

    Langeslag, Sandra J E; van der Veen, Frederik M; Röder, Christian H

    2014-02-01

    In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved-related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved-distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved-related information per se, but only by beloved-related information that is attended. Copyright © 2012 Wiley Periodicals, Inc.

  19. File list: Pol.Neu.50.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.AllAg.Corpus_Striatum mm9 RNA polymerase Neural Corpus Striatum SRX65717...3,SRX657178,SRX657174,SRX657179 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Corpus_Striatum.bed ...

  20. File list: ALL.Neu.50.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.50.AllAg.Corpus_Striatum mm9 All antigens Neural Corpus Striatum SRX686035,...033,SRX148353,SRX657170,SRX657175,SRX323781,SRX148352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.50.AllAg.Corpus_Striatum.bed ...

  1. File list: Unc.Neu.20.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.20.AllAg.Corpus_Striatum mm9 Unclassified Neural Corpus Striatum SRX148357,...SRX148356 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.20.AllAg.Corpus_Striatum.bed ...

  2. File list: InP.Neu.20.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Neu.20.AllAg.Corpus_Striatum mm9 Input control Neural Corpus Striatum SRX686031...,SRX686032,SRX657175,SRX657170 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.20.AllAg.Corpus_Striatum.bed ...

  3. File list: ALL.Neu.10.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.10.AllAg.Corpus_Striatum mm9 All antigens Neural Corpus Striatum SRX686034,...355,SRX657170,SRX657175,SRX148352,SRX686037,SRX148353 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.10.AllAg.Corpus_Striatum.bed ...

  4. File list: Pol.Neu.10.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.10.AllAg.Corpus_Striatum mm9 RNA polymerase Neural Corpus Striatum SRX65717...4,SRX657179,SRX657173,SRX657178 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Corpus_Striatum.bed ...

  5. File list: His.Neu.10.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Corpus_Striatum mm9 Histone Neural Corpus Striatum SRX686034,SRX68...686038,SRX686037 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Corpus_Striatum.bed ...

  6. File list: ALL.Neu.05.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Corpus_Striatum mm9 All antigens Neural Corpus Striatum SRX686038,...356,SRX148353,SRX148355,SRX657170,SRX657175,SRX148352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Corpus_Striatum.bed ...

  7. File list: InP.Neu.50.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Neu.50.AllAg.Corpus_Striatum mm9 Input control Neural Corpus Striatum SRX686031...,SRX686032,SRX657170,SRX657175 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.50.AllAg.Corpus_Striatum.bed ...

  8. File list: Unc.Neu.05.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.05.AllAg.Corpus_Striatum mm9 Unclassified Neural Corpus Striatum SRX148357,...SRX148356 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.05.AllAg.Corpus_Striatum.bed ...

  9. File list: Unc.Neu.50.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Corpus_Striatum mm9 Unclassified Neural Corpus Striatum SRX148357,...SRX148356 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Corpus_Striatum.bed ...

  10. File list: Oth.Neu.10.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.10.AllAg.Corpus_Striatum mm9 TFs and others Neural Corpus Striatum SRX14835...4,SRX148355,SRX148352,SRX148353 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.10.AllAg.Corpus_Striatum.bed ...

  11. File list: InP.Neu.10.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Neu.10.AllAg.Corpus_Striatum mm9 Input control Neural Corpus Striatum SRX686031...,SRX686032,SRX657170,SRX657175 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.10.AllAg.Corpus_Striatum.bed ...

  12. File list: Oth.Neu.50.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.AllAg.Corpus_Striatum mm9 TFs and others Neural Corpus Striatum SRX14835...4,SRX148355,SRX148353,SRX148352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Corpus_Striatum.bed ...

  13. File list: His.Neu.20.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.20.AllAg.Corpus_Striatum mm9 Histone Neural Corpus Striatum SRX323783,SRX68...686034,SRX686033 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.20.AllAg.Corpus_Striatum.bed ...

  14. File list: Pol.Neu.05.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.AllAg.Corpus_Striatum mm9 RNA polymerase Neural Corpus Striatum SRX65717...4,SRX657179,SRX657178,SRX657173 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.05.AllAg.Corpus_Striatum.bed ...

  15. File list: InP.Neu.05.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Neu.05.AllAg.Corpus_Striatum mm9 Input control Neural Corpus Striatum SRX686032...,SRX686031,SRX657170,SRX657175 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.05.AllAg.Corpus_Striatum.bed ...

  16. File list: Pol.Neu.20.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.AllAg.Corpus_Striatum mm9 RNA polymerase Neural Corpus Striatum SRX65717...3,SRX657178,SRX657179,SRX657174 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.AllAg.Corpus_Striatum.bed ...

  17. File list: Oth.Neu.20.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.20.AllAg.Corpus_Striatum mm9 TFs and others Neural Corpus Striatum SRX14835...4,SRX148355,SRX148353,SRX148352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Corpus_Striatum.bed ...

  18. File list: Oth.Neu.05.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.05.AllAg.Corpus_Striatum mm9 TFs and others Neural Corpus Striatum SRX14835...4,SRX148353,SRX148355,SRX148352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.05.AllAg.Corpus_Striatum.bed ...

  19. File list: Unc.Neu.10.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.10.AllAg.Corpus_Striatum mm9 Unclassified Neural Corpus Striatum SRX148357,...SRX148356 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.10.AllAg.Corpus_Striatum.bed ...

  20. File list: ALL.Neu.20.AllAg.Corpus_Striatum [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.20.AllAg.Corpus_Striatum mm9 All antigens Neural Corpus Striatum SRX323783,...034,SRX686033,SRX148353,SRX657175,SRX657170,SRX148352 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.20.AllAg.Corpus_Striatum.bed ...

  1. Seasonal shifts in body temperature and use of microhabitats by Galapagos land iguanas (Conolophus pallidus)

    Energy Technology Data Exchange (ETDEWEB)

    Christian, K.; Tracy, C.R.; Porter, W.P.

    1983-06-01

    Seasonal differences in the body temperatures (T/sub b/) of free-ranging Galapagos land iguanas (Conolophus pallidus) were detected by temperature sensitive telemetry transmitters. Midday T/sub b/'s of iguanas average 4.4/sup 0/C lower in the Garua (cool) season than in the Hot season. Measured T/sub b/'s and those predicted from biophysical models permitted the following conclusions: (1) lower T/sub b/'s during the Garua season represent an active shift in thermoregulation by the iguanas rather than a passive result of a cooler season; (2) the average midday T/sub b/ selected by the iguanas in either season is the T/sub b/ that allows maintenance of a constant T/sub b/ for the longest possible portion of the day; (3) by exploiting the warmer microclimate created by a cliff face, the iguanas are able to maintain a constant T/sub b/ for a full hour longer than they could elsewhere in their home range. Census data demonstrated that the iguanas exploited the warmer microclimate created by the cliff extensively during the Garua season, and the cliff face was visited by the iguanas relatively infrequently during the Hot season. Thus, the exploitation of the microclimate created by the cliff results in seasonal differences in the pattern of space utilization within the home ranges of the iguanas. Within the Garua season the iguanas moved away from the cliff more often on sunny days than during cloudy days. It is concluded that the physical environment is an important determinant of patterns of space utilization both within and between seasons.

  2. Glycinergic inhibition of BAT sympathetic premotor neurons in rostral raphe pallidus.

    Science.gov (United States)

    Conceição, Ellen Paula Santos da; Madden, Christopher J; Morrison, Shaun F

    2017-06-01

    The rostral raphe pallidus (rRPa) contains sympathetic premotor neurons controlling thermogenesis in brown adipose tissue (BAT). We sought to determine whether a tonic activation of glycine A receptors (Gly A R) in the rRPa contributes to the inhibitory regulation of BAT sympathetic nerve activity (SNA) and of cardiovascular parameters in anesthetized rats. Nanoinjection of the Gly A R antagonist, strychnine (STR), into the rRPa of intact rats increased BAT SNA (peak: +495%), BAT temperature (T BAT , +1.1°C), expired CO 2 , (+0.4%), core body temperature (T CORE , +0.2°C), mean arterial pressure (MAP, +4 mmHg), and heart rate (HR, +57 beats/min). STR into rRPa in rats with a postdorsomedial hypothalamus transection produced similar increases in BAT thermogenic and cardiovascular parameters. Glycine nanoinjection into the rRPa evoked a potent inhibition of the cooling-evoked increases in BAT SNA (nadir: -74%), T BAT (-0.2°C), T CORE (-0.2°C), expired CO 2 (-0.2%), MAP (-8 mmHg), and HR (-22 beats/min) but had no effect on the increases in these variables evoked by STR nanoinjection into rRPa. Nanoinjection of GABA into the rRPa inhibited the STR-evoked BAT SNA (nadir: -86%) and reduced the expired CO 2 (-0.4%). Blockade of glutamate receptors in rRPa reduced the STR-evoked increases in BAT SNA (nadir: -61%), T BAT (-0.5°C), expired CO 2 (-0.3%), MAP (-9 mmHg), and HR (-33 beats/min). We conclude that a tonically active glycinergic input to the rRPa contributes to the inhibitory regulation of the discharge of BAT sympathetic premotor neurons and of BAT thermogenesis and energy expenditure. Copyright © 2017 the American Physiological Society.

  3. Parvalbumin and calbindin expression in parallel thalamocortical pathways in a gleaning bat, Antrozous pallidus.

    Science.gov (United States)

    Martin del Campo, Heather; Measor, Kevin; Razak, Khaleel A

    2014-07-01

    The pallid bat (Antrozous pallidus) listens to prey-generated noise to localize and hunt terrestrial prey while reserving echolocation to avoid obstacles. The thalamocortical connections in the pallid bat are organized as parallel pathways that may serve echolocation and prey localization behaviors. Thalamic inputs to the cortical echolocation call- and noise-selective regions originate primarily in the suprageniculate nucleus (SG) and ventral division of medial geniculate body (MGBv), respectively. Here we examined the distribution of parvalbumin (PV) and calbindin (CB) expression in cortical regions and thalamic nuclei of these pathways. Electrophysiology was used to identify cortical regions selective for echolocation calls and noise. Immunohistochemistry was used to stain for PV and CB in the auditory cortex and MGB. A higher percentage (relative to Nissl-stained cells) of PV(+) cells compared with CB(+) cells was found in both echolocation call- and noise-selective regions. This was due to differences in cortical layers V-VI, but not layers I-IV. In the MGB, CB(+) cells were present across all divisions of the MGB, with a higher percentage in the MGBv than the SG. Perhaps the most surprising result was the virtual absence of PV staining in the MGBv. PV staining was present only in the SG. Even in the SG, the staining was mostly diffuse in the neuropil. These data support the notion that calcium binding proteins are differentially distributed in different processing streams. Our comparative data, however, do not support a general mammalian pattern of PV/CB staining that distinguishes lemniscal and nonlemniscal pathways. Copyright © 2014 Wiley Periodicals, Inc.

  4. Arizona bark scorpion venom resistance in the pallid bat, Antrozous pallidus.

    Directory of Open Access Journals (Sweden)

    Bradley H Hopp

    Full Text Available The pallid bat (Antrozous pallidus, a gleaning bat found in the western United States and Mexico, hunts a wide variety of ground-dwelling prey, including scorpions. Anecdotal evidence suggests that the pallid bat is resistant to scorpion venom, but no systematic study has been performed. Here we show with behavioral measures and direct injection of venom that the pallid bat is resistant to venom of the Arizona bark scorpion, Centruroides sculpturatus. Our results show that the pallid bat is stung multiple times during a hunt without any noticeable effect on behavior. In addition, direct injection of venom at mouse LD50 concentrations (1.5 mg/kg has no effect on bat behavior. At the highest concentration tested (10 mg/kg, three out of four bats showed no effects. One of the four bats showed a transient effect suggesting that additional studies are required to identify potential regional variation in venom tolerance. Scorpion venom is a cocktail of toxins, some of which activate voltage-gated sodium ion channels, causing intense pain. Dorsal root ganglia (DRG contain nociceptive neurons and are principal targets of scorpion venom toxins. To understand if mutations in specific ion channels contribute to venom resistance, a pallid bat DRG transcriptome was generated. As sodium channels are a major target of scorpion venom, we identified amino acid substitutions present in the pallid bat that may lead to venom resistance. Some of these substitutions are similar to corresponding amino acids in sodium channel isoforms responsible for reduced venom binding activity. The substitution found previously in the grasshopper mouse providing venom resistance to the bark scorpion is not present in the pallid bat, indicating a potentially novel mechanism for venom resistance in the bat that remains to be identified. Taken together, these results indicate that the pallid bat is resistant to venom of the bark scorpion and altered sodium ion channel function may

  5. Functional neuroanatomy of the basal ganglia as studied by dual-probe microdialysis

    International Nuclear Information System (INIS)

    O'Connor, William T.

    1998-01-01

    Dual probe microdialysis was employed in intact rat brain to investigate the effect of intrastriatal perfusion with selective dopamine D 1 and D 2 receptor agonists and with c-fos antisense oligonucleotide on (a) local GABA release in the striatum; (b) the internal segment of the globus pallidus and the substantia nigra pars reticulata, which is the output site of the strionigral GABA pathway; and (c) the external segment of the globus pallidus, which is the output site of the striopallidal GABA pathway. The data provide functional in vivo evidence for a selective dopamine D 1 receptor-mediated activation of the direct strionigral GABA pathway and a selective dopamine D 2 receptor inhibition of the indirect striopallidal GABA pathway and provides a neuronal substrate for parallel processing in the basal ganglia regulation of motor function. Taken together, these findings offer new therapeutic strategies for the treatment of dopamine-linked disorders such as Parkinson's disease, Huntington's disease, and schizophrenia

  6. Spike-timing dependent plasticity in the striatum

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    2010-06-01

    Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.

  7. Aversive Counterconditioning Attenuates Reward Signaling in the Ventral Striatum.

    Science.gov (United States)

    Kaag, Anne Marije; Schluter, Renée S; Karel, Peter; Homberg, Judith; van den Brink, Wim; Reneman, Liesbeth; van Wingen, Guido A

    2016-01-01

    Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient reward such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional magnetic resonance imaging (fMRI). In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signaling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signaling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula.

  8. Continuous cultivation of a thermophilic bacterium Aeribacillus pallidus 418 for production of an exopolysaccharide applicable in cosmetic creams.

    Science.gov (United States)

    Radchenkova, N; Panchev, I; Vassilev, S; Kuncheva, M; Dobreva, S; Kambourova, M

    2015-11-01

    The aim of this study was to evaluate the effectiveness of continuous cultivation approach for exopolysaccharide (EPS) production by a thermophilic micro-organism and the potential of the synthesized EPS for application in cosmetic industry. Study on the ability of Aeribacillus pallidus 418, isolated as a good EPS producer, to synthesize the polymer in continuous cultures showed higher production in comparison with batch cultures. The degree of the EPS in the precipitate after continuous cultivation significantly increased. Non-Newtonian pseudoplastic and thixotropic behaviour of EPS determines the ability of the received cream to become more fluid after increasing time of application on the skin. This study demonstrates a highly efficient way for production of EPS from a continuous growth culture of A. pallidus 418 that have many advantages and can outperform batch culture by eliminating time for cleaning and sterilization of the vessel and the comparatively long lag phases before the organisms enter a brief period of high productivity. The valuable physico-chemical properties of the synthesized EPS influenced positively the properties of a commercial cream. EPSs from thermophilic micro-organisms are of special interest due to the advantages of the thermophilic processes and nonpathogenic nature of the polymer molecules. However, their industrial application is hindered by the comparatively low biomass and correspondingly EPS yield. Suggested continuous approach for EPS could have an enormous economic potential for an industrial scale production of thermophilic EPSs. © 2015 The Society for Applied Microbiology.

  9. Zero-Dimensional Model to Study the Effectiveness of Plasma Heating and Thermal Energy Confinement in Globus-M Tokamak in Ohmic Heating Modes

    Science.gov (United States)

    Kurskiev, G. S.; Sakharov, N. V.; Schegolev, P. B.; Bakharev, N. N.; Kiselev, E. O.; Avdeeva, G. F.; Gusev, V. K.; Iblyaminova, A. D.; Minaev, V. B.; Miroshnikov, I. V.; Patrov, M. I.; Petrov, Yu. V.; Telnova, A. Yu.; Tolstyakov, S. Yu.; Tokarev, V. A.

    2017-12-01

    Experimental study of thermal energy confinement in magnetic confinement devices is one of the fundamental problems in plasma physics. The data processing technique covering kinetic and magnetic measurements performed for the Globus-M tokamak is described. A zero-dimensional code has been developed on the basis of this approach making it possible to calculate important discharge parameters during the experiment (between discharges): the electron and ion stored thermal energy content, plasma effective charge, and confinement time. Good agreement of the zero-dimensional calculations and ASTRA modeling indicates that this approach can be applied for routine data processing in Globus-M in view of the specifics of the device.

  10. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...

  11. Draft Genome Sequence of Aeribacillus pallidus Strain 8m3, a Thermophilic Hydrocarbon-Oxidizing Bacterium Isolated from the Dagang Oil Field (China).

    Science.gov (United States)

    Poltaraus, Andrey B; Sokolova, Diyana S; Grouzdev, Denis S; Ivanov, Timophey M; Malakho, Sophia G; Korshunova, Alena V; Rozanov, Aleksey S; Tourova, Tatiyana P; Nazina, Tamara N

    2016-06-09

    The draft genome sequence of Aeribacillus pallidus strain 8m3, a thermophilic aerobic oil-oxidizing bacterium isolated from production water from the Dagang high-temperature oil field, China, is presented here. The genome is annotated to provide insights into the genomic and phenotypic diversity of the genus Aeribacillus. Copyright © 2016 Poltaraus et al.

  12. Draft Genome Sequence of Aeribacillus pallidus Strain 8m3, a Thermophilic Hydrocarbon-Oxidizing Bacterium Isolated from the Dagang Oil Field (China)

    OpenAIRE

    Poltaraus, Andrey B.; Sokolova, Diyana S.; Grouzdev, Denis S.; Ivanov, Timophey M.; Malakho, Sophia G.; Korshunova, Alena V.; Rozanov, Aleksey S.; Tourova, Tatiyana P.; Nazina, Tamara N.

    2016-01-01

    The draft genome sequence of Aeribacillus pallidus strain 8m3, a thermophilic aerobic oil-oxidizing bacterium isolated from production water from the Dagang high-temperature oil field, China, is presented here. The genome is annotated to provide insights into the genomic and phenotypic diversity of the genus Aeribacillus.

  13. Exploring personality traits related to dopamine D2/3 receptor availability in striatal subregions of humans.

    Science.gov (United States)

    Caravaggio, Fernando; Fervaha, Gagan; Chung, Jun Ku; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

    2016-04-01

    While several studies have examined how particular personality traits are related to dopamine D2/3 receptor (D2/3R) availability in the striatum of humans, few studies have reported how multiple traits measured in the same persons are differentially related to D2/3R availability in different striatal sub-regions. We examined how personality traits measured with the Karolinska Scales of Personality are related to striatal D2/3R availability measured with [(11)C]-raclopride in 30 healthy humans. Based on previous the literature, five personality traits were hypothesized to be most likely related to D2/3R availability: impulsiveness, monotony avoidance, detachment, social desirability, and socialization. We found self-reported impulsiveness was negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. After controlling for age and gender, monotony avoidance was also negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. Socialization was positively correlated with D2/3R availability in the ventral striatum and putamen. After controlling for age and gender, the relationship between socialization and D2/3R availability in these regions survived correction for multiple comparisons (p-threshold=.003). Thus, within the same persons, different personality traits are differentially related to in vivo D2/3R availability in different striatal sub-regions. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  14. Chemical architecture of the posterior striatum in the human brain.

    Science.gov (United States)

    Bernácer, J; Prensa, L; Giménez-Amaya, J M

    2008-01-01

    The neurochemical organization of the posterior caudate nucleus (CN) (body, gyrus and tail) and putamen (Put) was analyzed in the human brain using adjacent sections stained for acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), enkephalin (ENK), parvalbumin (PV), calbindin (CB) and tyrosine hydroxylase (TH). Striosomes were visualized in all striatal regions but the anterior two thirds of the CN tail. They were highly immunoreactive (-ir) for ENK and LAMP, devoid of PV and AChE staining, and surrounded by a ring of tissue with pale TH- and CB-ir neuropil. In the Put, other rings of tissue completely free of ENK labeling surrounded certain striosomes (clear septa). In the CN body, gyrus and tail some markers revealed gradients and heterogeneities along the dorsoventral and mediolateral axes. A rim of striatal tissue densely stained for ENK and LAMP and poorly labeled for PV was noticeable along the lateral edge of the Put and the dorsolateral sector of the CN body. Our results illustrate a chemical architecture in the posterior striatum that is heterogeneous and slightly different from that found in the more anterior striatum.

  15. Kinetic diversity of dopamine transmission in the dorsal striatum.

    Science.gov (United States)

    Taylor, I Mitch; Nesbitt, Kathryn M; Walters, Seth H; Varner, Erika L; Shu, Zhan; Bartlow, Kathleen M; Jaquins-Gerstl, Andrea S; Michael, Adrian C

    2015-05-01

    Dopamine (DA), a highly significant neurotransmitter in the mammalian central nervous system, operates on multiple time scales to affect a diverse array of physiological functions. The significance of DA in human health is heightened by its role in a variety of pathologies. Voltammetric measurements of electrically evoked DA release have brought to light the existence of a patchwork of DA kinetic domains in the dorsal striatum (DS) of the rat. Thus, it becomes necessary to consider how these domains might be related to specific aspects of DA's functions. Responses evoked in the fast and slow domains are distinct in both amplitude and temporal profile. Herein, we report that responses evoked in fast domains can be further classified into four distinct types, types 1-4. The DS, therefore, exhibits a total of at least five distinct evoked responses (four fast types and one slow type). All five response types conform to kinetic models based entirely on first-order rate expressions, which indicates that the heterogeneity among the response types arises from kinetic diversity within the DS terminal field. We report also that functionally distinct subregions of the DS express DA kinetic diversity in a selective manner. Thus, this study documents five response types, provides a thorough kinetic explanation for each of them, and confirms their differential association with functionally distinct subregions of this key DA terminal field. The dorsal striatum is composed of five significantly different dopamine domains (types 1-4 and slow, average ± SEM responses to medial forebrain bundle (MFB) stimulation are shown in the figure). Responses from each of these five domains exhibit significantly different ascending and descending kinetic profiles and return to a long lasting elevated dopamine state, termed the dopamine hang-up. All features of these responses are modeled with high correlation using first-order modeling as well as our recently published restricted diffusion

  16. Language Processing within the Striatum: Evidence from a PET Correlation Study in Huntington's Disease

    Science.gov (United States)

    Teichmann, Marc; Gaura, Veronique; Demonet, Jean-Francois; Supiot, Frederic; Delliaux, Marie; Verny, Christophe; Renou, Pierre; Remy, Philippe; Bachoud-Levi, Anne-Catherine

    2008-01-01

    The role of sub-cortical structures in language processing, and more specifically of the striatum, remains controversial. In line with psycholinguistic models stating that language processing implies both the recovery of lexical information and the application of combinatorial rules, the striatum has been claimed to be involved either in the…

  17. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    NARCIS (Netherlands)

    Willuhn, Ingo; Burgeno, Lauren M; Groblewski, Peter A; Phillips, Paul E M

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

  18. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    NARCIS (Netherlands)

    Willuhn, Ingo; Burgeno, Lauren M.; Groblewski, Peter A.; Phillips, Paul E. M.

    2014-01-01

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

  19. Art for reward's sake: visual art recruits the ventral striatum.

    Science.gov (United States)

    Lacey, Simon; Hagtvedt, Henrik; Patrick, Vanessa M; Anderson, Amy; Stilla, Randall; Deshpande, Gopikrishna; Hu, Xiaoping; Sato, João R; Reddy, Srinivas; Sathian, K

    2011-03-01

    A recent study showed that people evaluate products more positively when they are physically associated with art images than similar non-art images. Neuroimaging studies of visual art have investigated artistic style and esthetic preference but not brain responses attributable specifically to the artistic status of images. Here we tested the hypothesis that the artistic status of images engages reward circuitry, using event-related functional magnetic resonance imaging (fMRI) during viewing of art and non-art images matched for content. Subjects made animacy judgments in response to each image. Relative to non-art images, art images activated, on both subject- and item-wise analyses, reward-related regions: the ventral striatum, hypothalamus and orbitofrontal cortex. Neither response times nor ratings of familiarity or esthetic preference for art images correlated significantly with activity that was selective for art images, suggesting that these variables were not responsible for the art-selective activations. Investigation of effective connectivity, using time-varying, wavelet-based, correlation-purged Granger causality analyses, further showed that the ventral striatum was driven by visual cortical regions when viewing art images but not non-art images, and was not driven by regions that correlated with esthetic preference for either art or non-art images. These findings are consistent with our hypothesis, leading us to propose that the appeal of visual art involves activation of reward circuitry based on artistic status alone and independently of its hedonic value. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Response inhibition signals and miscoding of direction in dorsomedial striatum

    Directory of Open Access Journals (Sweden)

    Daniel W Bryden

    2012-09-01

    Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

  1. Chemical heterogeneity of the striosomal compartment in the human striatum.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A

    1999-11-01

    The neurochemical organization of the striosomal compartment in the human striatum was analyzed by histochemical and immunohistochemical techniques applied to postmortem tissue from normal individuals. The striosomes were delineated by using the following markers: acetylcholinesterase (AChE), enkephalin (ENK), substance P (SP), calbindin-D28k (CB), parvalbumin (PV), calretinin (CR), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and NADPH-diaphorase. Comparisons were made between striosomal boundaries, as outlined by each marker applied on adjacent sections, and particular attention was paid to possible variations in the chemical features of striosomes along the rostrocaudal extent of the striatum. The main findings of this study are as follows: 1) the striosomal compartment is composed of two chemically distinct domains: a core and a peripheral region; 2) the core is largely devoid of CB and displays a less intense staining for ENK and LAMP than the peripheral region; 3) although striosomes are largely devoid of AChE, the activity of this enzyme is slightly higher in the core than in the peripheral region; 4) the core and peripheral regions are weakly stained for PV and intensely stained for SP; 5) ChAT-, CR- and NADPH-diaphorase-positive neurons are preferentially distributed in the peripheral region; 6) at rostral striatal levels, striosomes are largely devoid of TH, whereas the inverse is true caudally; and 7) at caudal striatal levels, the peripheral region of striosomes is intensely stained for CB and ChAT. These results demonstrate that the striosomes in human display a strikingly complex and heterogeneous chemical architecture. Copyright 1999 Wiley-Liss, Inc.

  2. Inhibiting PKM[zeta] Reveals Dorsal Lateral and Dorsal Medial Striatum Store the Different Memories Needed to Support Adaptive Behavior

    Science.gov (United States)

    Pauli, Wolfgang M.; Clark, Alexandra D.; Guenther, Heidi J.; O'Reilly, Randall C.; Rudy, Jerry W.

    2012-01-01

    Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or…

  3. Alleviation of overtraining reversal effect by transient inactivation of the dorsal striatum.

    Science.gov (United States)

    Van Golf Racht-Delatour, B; Massioui, N E

    2000-09-01

    In this study, we investigated the role of the dorsal striatum in the acquisition and the use (retrieval) of a specific learning developed during overtraining. The paradigm was such that rats had to respond differentially to two signals in order to obtain food or to avoid an electrical footshock. Overtraining was aimed at eliciting a facilitative effect on discrimination reversal as compared to simply trained rats. In this way, transient inactivation of the dorsal striatum by lidocaine enabled us to investigate, separately, the role of this structure during overtraining and reversal. The data show that inactivating the dorsal striatum before each reversal session prevented the overtraining reversal effect observed in control rats. Moreover, inactivation of the dorsal striatum during overtraining had no effect on the level of discriminative performance just as it did not affect the subsequent facilitative effect on reversal. These results show that even though the striatum might normally be part of a routine automatic system, clearly its contribution is not essential. Indeed, despite inactivation of the striatum in overtrained rats, their ability to develop an efficient selection process that can be used during reversal was observed. However, the integrity of the striatum became essential in order to mediate the modification of behaviour when this behavioural routine formed during overtraining had to be modified during reversal.

  4. Ventral and Dorsal Striatum Networks in Obesity: Link to Food Craving and Weight Gain.

    Science.gov (United States)

    Contreras-Rodríguez, Oren; Martín-Pérez, Cristina; Vilar-López, Raquel; Verdejo-Garcia, Antonio

    2017-05-01

    The food addiction model proposes that obesity overlaps with addiction in terms of neurobiological alterations in the striatum and related clinical manifestations (i.e., craving and persistence of unhealthy habits). Therefore, we aimed to examine the functional connectivity of the striatum in excess-weight versus normal-weight subjects and to determine the extent of the association between striatum connectivity and individual differences in food craving and changes in body mass index (BMI). Forty-two excess-weight participants (BMI > 25) and 39 normal-weight participants enrolled in the study. Functional connectivity in the ventral and dorsal striatum was indicated by seed-based analyses on resting-state data. Food craving was indicated with subjective ratings of visual cues of high-calorie food. Changes in BMI between baseline and 12 weeks follow-up were assessed in 28 excess-weight participants. Measures of connectivity in the ventral striatum and dorsal striatum were compared between groups and correlated with craving and BMI change. Participants with excess weight displayed increased functional connectivity between the ventral striatum and the medial prefrontal and parietal cortices and between the dorsal striatum and the somatosensory cortex. Dorsal striatum connectivity correlated with food craving and predicted BMI gains. Obesity is linked to alterations in the functional connectivity of dorsal striatal networks relevant to food craving and weight gain. These neural alterations are associated with habit learning and thus compatible with the food addiction model of obesity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Cerebral glucose metabolism in Parkinson's disease

    International Nuclear Information System (INIS)

    Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

    1984-01-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

  6. Effects of aging on nitrergic system in human basal nuclei

    Directory of Open Access Journals (Sweden)

    Bruno Lopes dos Santos

    2014-10-01

    Full Text Available Nitric oxide (NO is a gaseous molecule that plays a role in a number of physiologic processes. The available evidence suggests that NO is a major neurotransmitter involved in motor control and emotion/behavior modulation. To investigate the distribution and morphology of the nitrergic system in human basal nuclei, we studied samples from the striatum, globus pallidus, subthalamic nucleus, substantia nigra and pedunculopontine nucleus of 20 human brains from subjects without neurologic/psychiatric diseases. The samples were stained for NADPH-diaphorase using histochemistry and for neuronal NO synthase using immunohistochemistry. We then analyzed the nitrergic neuronal density and its morphometric parameters. Our data demonstrated that: (I the most posterior regions of the striatum exhibit a higher neuronal density; (II the limbic cortex-associated areas of the striatum exhibit higher neuronal density than other functional subdivisions; (III approximately 90% of the neurons in the subthalamic nucleus express NO; (IV the pedunculopontine nucleus exhibits a massive nitrergic neuronal density; (V in the globus pallidus, there is a marked presence of NO neurons in the medial medullary lamina; and (VI nitrergic neurons were not detected in the substantia nigra. Aging did not change the neuronal density or the morphometric parameters of nitrergic neurons in the analyzed nuclei.

  7. The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

    Science.gov (United States)

    Cole, Sindy; Stone, Andrew D; Petrovich, Gorica D

    2017-12-01

    The dorsomedial striatum (DMS) is an important sensorimotor region mediating the acquisition of goal-directed instrumental reward learning and behavioral flexibility. However, whether the DMS also regulates Pavlovian cue-food learning is less clear. The current study used excitotoxic lesions to determine whether the DMS is critical in Pavlovian appetitive learning and behavior, using discriminative conditioning and reversal paradigms. The results showed that DMS lesions transiently retarded cue-food learning and subsequent reversal of this learning. Rats with DMS lesions selectively attenuated responding to a food cue but not a control cue, early in training, suggesting the DMS is involved when initial associations are formed. Similarly, initial reversal learning was attenuated in rats with DMS lesions, which suggests impaired flexibility to adjust behavior when the cue meaning is reversed. We also examined the effect of DMS lesions on food intake during tests with access to a highly palatable food along with standard chow diet. Rats with DMS lesions showed an altered pattern of intake, with an initial reduction in high-fat diet followed by an increase in chow consumption. These results demonstrate that the DMS has a role in mediating cue-food learning and its subsequent reversal, as well as changes in food intake when a choice is provided. Together, these results demonstrate the DMS is involved in reward associative learning and reward consumption, when behavioral flexibility is needed to adjust responding or consumption to match the current value. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

    Directory of Open Access Journals (Sweden)

    Todd M. Mowery

    2017-06-01

    Full Text Available Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL, are commonly linked with processing deficits at or below the level of the auditory cortex (ACx. However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, adult ACx neurons recovered balanced excitatory-inhibitory synaptic gain and control-like firing rates, but striatal neuron synapses and firing properties did not recover. Thus, a brief period of abnormal cortical activity may induce cellular impairments that persist into adulthood and contribute to neurological disorders that are striatal in origin.

  9. An Extended Design of the "Grid-Enabled SEE++ System" Based on Globus Toolkit 4 and gLite Conference

    CERN Document Server

    Schreiner, W.; Buchberger, M.; Kaltofen, T.

    2006-01-01

    "Grid-Enabled SEE++" based on the SEE++ software system for the biomechanical 3D simulation of the human eye and its muscles. SEE++ simulates the common eye muscle surgery techniques in a graphic interactive way that is familiar to an experienced surgeon. The goal of "Grid-Enabled SEE++" is to adapt and to extend SEE++ in several steps and to develop an efficient grid-based tool for "Evidence Based Medicine", which supports the surgeons in choosing optimal surgery techniques for the treatments of different syndromes of strabismus. In our previous work, we combined the SEE++ software with the Globus (pre-Web Service) middleware and developed a parallel version of the simulation of the "Hess-Lancaster test" (typical medical examination). By this, we demonstrated how a noticeable speedup can be achieved in SEE++ by the exploitation of the computational power of the Grid. Furthermore, we reported the prototype implementation of a medical database component for "Grid-Enabled SEE++". Finally, we designed a so calle...

  10. Dissociated sequential activity and stimulus encoding in the dorsomedial striatum during spatial working memory.

    Science.gov (United States)

    Akhlaghpour, Hessameddin; Wiskerke, Joost; Choi, Jung Yoon; Taliaferro, Joshua P; Au, Jennifer; Witten, Ilana B

    2016-09-16

    Several lines of evidence suggest that the striatum has an important role in spatial working memory. The neural dynamics in the striatum have been described in tasks with short delay periods (1-4 s), but remain largely uncharacterized for tasks with longer delay periods. We collected and analyzed single unit recordings from the dorsomedial striatum of rats performing a spatial working memory task with delays up to 10 s. We found that neurons were activated sequentially, with the sequences spanning the entire delay period. Surprisingly, this sequential activity was dissociated from stimulus encoding activity, which was present in the same neurons, but preferentially appeared towards the onset of the delay period. These observations contrast with descriptions of sequential dynamics during similar tasks in other brains areas, and clarify the contribution of the striatum to spatial working memory.

  11. Task-specific contribution of the human striatum to perceptual-motor skill learning.

    Science.gov (United States)

    Cavaco, Sara; Anderson, Steven W; Correia, Manuel; Magalhaes, Marina; Pereira, Claudia; Tuna, Assuncao; Taipa, Ricardo; Pinto, Pedro; Pinto, Claudia; Cruz, Romeu; Lima, Antonio Bastos; Castro-Caldas, Alexandre; da Silva, Antonio Martins; Damasio, Hanna

    2011-01-01

    Acquisition of new perceptual-motor skills depends on multiple brain areas, including the striatum. However, the specific contribution of each structure to this type of learning is still poorly understood. Focusing on the striatum, we proposed (a) to replicate the finding of impaired rotary pursuit (RP) and preserved mirror tracing (MT) in Huntington's disease (HD); and (b) to further explore this putative learning dissociation with other human models of striatal dysfunction (i.e., Parkinson's disease and focal vascular damage) and two new paradigms (i.e., Geometric Figures, GF, and Control Stick, CS) of skill learning. Regardless of the etiology, participants with damage to the striatum showed impaired learning of visuomotor tracking skills (i.e., RP and GF), whereas the ability to learn skills that require motor adaptation (i.e., MT and CS) was not affected. These results suggest a task-specific involvement of the striatum in the early stages of skill learning.

  12. Human dorsal striatum encodes prediction errors during observational learning of instrumental actions.

    Science.gov (United States)

    Cooper, Jeffrey C; Dunne, Simon; Furey, Teresa; O'Doherty, John P

    2012-01-01

    The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of others. In this study, we investigated the extent to which human dorsal striatum is involved in observational as well as experiential instrumental reward learning. Human participants were scanned with fMRI while they observed a confederate over a live video performing an instrumental conditioning task to obtain liquid juice rewards. Participants also performed a similar instrumental task for their own rewards. Using a computational model-based analysis, we found reward prediction errors in the dorsal striatum not only during the experiential learning condition but also during observational learning. These results suggest a key role for the dorsal striatum in learning instrumental associations, even when those associations are acquired purely by observing others.

  13. Dopaminergic modulation of the functional ventrodorsal architecture of the human striatum

    NARCIS (Netherlands)

    Piray, P.; Ouden, H.E.M. den; Schaaf, M.E. van der; Toni, I.; Cools, R.

    2017-01-01

    Interactions between motivational, cognitive, and motor regions of the striatum are crucial for implementing behavioral control. Work with experimental animals indicates that such interactions are sensitive to modulation by dopamine. Using systematic pharmacological manipulation of dopamine

  14. Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction.

    Science.gov (United States)

    Brand, Matthias; Snagowski, Jan; Laier, Christian; Maderwald, Stefan

    2016-04-01

    One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Comparative imaging study on monkeys with hemi-parkinsonism

    International Nuclear Information System (INIS)

    Wang Wei; Yu Xiaoping; Mao Jun; Liu Sheng; Wang Xiaoyi; Peng Guangchun; Wang Ruiwen

    2003-01-01

    Objective: To study the imaging appearance of experimental Parkinson's disease (PD) and to evaluate the different medical imaging exams on PD. Methods: CT, MRI, SPECT (dopamine transporter imaging and regional cerebral blood flow imaging, DAT imaging and rCBF imaging), and PET (glucose metabolism imaging) were performed on 8 monkeys before and after the infusion of MPTP into unilateral internal carotid artery to develop hemi-Parkinsonism models. Results: Hemi-Parkinsonism models were successfully induced on all 8 monkeys. On DAT imaging, the uptake values of the lesioned striatums decreased obviously after the MPTP treatment and were lower than that of the contralateral ones. The glucose metabolic rates of the lesioned striatums and thalamus in PD models were lower, compared to that of the healthy monkeys and that of the contralateral sides of themselves. Neither DAT nor glucose metabolism abnormalities was found on both the contralateral sides of the healthy and PD monkeys. On MRI images before MPTP treatment, only 4 of 8 PD models showed hypointense in bilateral globus pallidus. No abnormal MRI findings occurred in the first 2 months after injection of MPTP. At tile third month, hypointense appeared in globus pallidus of three monkeys. Enlarged hyposignal region in globus pallidus were found in three models. Of the above 6 monkeys, two appeared hypointense in putamina. Substantia nigra demonstrated no abnormalities before and after MPTP treatment. All rCBF and CT images were normal. Conclusion: The decreased density of DAT and decreased glucose metabolism on experimental PD can be showed early by DAT imaging and glucose metabolism imaging, MRI can show abnormal signal in the basal ganglia of PD but it is later than DAT and glucose metabolism imaging. CT and rCBF find no abnormality on PD

  16. Ventromedial Prefrontal Cortex Damage Is Associated with Decreased Ventral Striatum Volume and Response to Reward.

    Science.gov (United States)

    Pujara, Maia S; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

    2016-05-04

    The ventral striatum and ventromedial prefrontal cortex (vmPFC) are two central nodes of the "reward circuit" of the brain. Human neuroimaging studies have demonstrated coincident activation and functional connectivity between these brain regions, and animal studies have demonstrated that the vmPFC modulates ventral striatum activity. However, there have been no comparable data in humans to address whether the vmPFC may be critical for the reward-related response properties of the ventral striatum. In this study, we used fMRI in five neurosurgical patients with focal vmPFC lesions to test the hypothesis that the vmPFC is necessary for enhancing ventral striatum responses to the anticipation of reward. In support of this hypothesis, we found that, compared with age- and gender-matched neurologically healthy subjects, the vmPFC-lesioned patients had reduced ventral striatal activity during the anticipation of reward. Furthermore, we observed that the vmPFC-lesioned patients had decreased volumes of the accumbens subregion of the ventral striatum. Together, these functional and structural neuroimaging data provide novel evidence for a critical role for the vmPFC in contributing to reward-related activity of the ventral striatum. These results offer new insight into the functional and structural interactions between key components of the brain circuitry underlying human affective function and decision-making. Maladaptive decision-making is a common problem across multiple mental health disorders. Developing new pathophysiologically based strategies for diagnosis and treatment thus requires a better understanding of the brain circuits responsible for adaptive decision-making and related psychological subprocesses (e.g., reward valuation, anticipation, and motivation). Animal studies provide evidence that these functions are mediated through direct interactions between two key nodes of a posited "reward circuit," the ventral striatum and the ventromedial prefrontal

  17. BAS-drive trait modulates dorsomedial striatum activity during reward response-outcome associations.

    Science.gov (United States)

    Costumero, Víctor; Barrós-Loscertales, Alfonso; Fuentes, Paola; Rosell-Negre, Patricia; Bustamante, Juan Carlos; Ávila, César

    2016-09-01

    According to the Reinforcement Sensitivity Theory, behavioral studies have found that individuals with stronger reward sensitivity easily detect cues of reward and establish faster associations between instrumental responses and reward. Neuroimaging studies have shown that processing anticipatory cues of reward is accompanied by stronger ventral striatum activity in individuals with stronger reward sensitivity. Even though establishing response-outcome contingencies has been consistently associated with dorsal striatum, individual differences in this process are poorly understood. Here, we aimed to study the relation between reward sensitivity and brain activity while processing response-reward contingencies. Forty-five participants completed the BIS/BAS questionnaire and performed a gambling task paradigm in which they received monetary rewards or punishments. Overall, our task replicated previous results that have related processing high reward outcomes with activation of striatum and medial frontal areas, whereas processing high punishment outcomes was associated with stronger activity in insula and middle cingulate. As expected, the individual differences in the activity of dorsomedial striatum correlated positively with BAS-Drive. Our results agree with previous studies that have related the dorsomedial striatum with instrumental performance, and suggest that the individual differences in this area may form part of the neural substrate responsible for modulating instrumental conditioning by reward sensitivity.

  18. PROJECTIONS OF DORSAL AND MEDIAN RAPHE NUCLEI TO DORSAL AND VENTRAL STRIATUM

    Directory of Open Access Journals (Sweden)

    G. R. Hassanzadeh G. Behzadi

    2007-08-01

    Full Text Available The ascending serotonergic projections are derived mainly from mesencephalic raphe nuclei. Topographical projections from mesencephalic raphe nuclei to the striatum were examined in the rat by the retrograde transport technique of HRP (horseradish peroxidase. In 29 rats stereotaxically injection of HRP enzyme were performed in dorsal and ventral parts of striatum separately. The extent of the injection sites and distribution of retrogradely labeled neuronal cell bodies were drawed on representative sections using a projection microscope. Following ipsilateral injection of HRP into the dorsal striatum, numerous labeled neurons were seen in rostral portion of dorsal raphe (DR nucleus. In the same level the cluster of labeled neurons were hevier through caudal parts of DR. A few neurons were also located in lateral wing of DR. More caudally some labeled neurons were found in lateral, medial line of DR. In median raphe nucleus (MnR the labeled neurons were scattered only in median portion of this nucleus. The ipsilateral injection of HRP into the ventral region of striatum resulted on labeling of numerous neurons in rostral, caudal and lateral portions of DR. Through the caudal extension of DR on 4th ventricle level, a large number of labeled neurons were distributed along the ventrocaudal parts of DR. In MnR, labeled neurons were observed only in median part of this nucleus. These findings suggest the mesencephalic raphe nuclei projections to caudo-putamen are topographically organized. In addition dorsal and median raphe nuclei have a stronger projection to the ventral striatum.

  19. Stable Encoding of Task Structure Coexists With Flexible Coding of Task Events in Sensorimotor Striatum

    Science.gov (United States)

    Kubota, Yasuo; Liu, Jun; Hu, Dan; DeCoteau, William E.; Eden, Uri T.; Smith, Anne C.

    2009-01-01

    The sensorimotor striatum, as part of the brain's habit circuitry, has been suggested to store fixed action values as a result of stimulus-response learning and has been contrasted with a more flexible system that conditionally assigns values to behaviors. The stability of neural activity in the sensorimotor striatum is thought to underlie not only normal habits but also addiction and clinical syndromes characterized by behavioral fixity. By recording in the sensorimotor striatum of mice, we asked whether neuronal activity acquired during procedural learning would be stable even if the sensory stimuli triggering the habitual behavior were altered. Contrary to expectation, both fixed and flexible activity patterns appeared. One, representing the global structure of the acquired behavior, was stable across changes in task cuing. The second, a fine-grain representation of task events, adjusted rapidly. Such dual forms of representation may be critical to allow motor and cognitive flexibility despite habitual performance. PMID:19625536

  20. "Zolotoi globus" dostalsja "Vaviljonu"

    Index Scriptorium Estoniae

    2007-01-01

    Kuldse Gloobuse auhinna draamakategoorias sai mängufilm "Paabel" ("Babel") : režissöör Alejandro Gonzalez Inarritu : Ameerika Ühendriigid - Mehhiko, 2006. Ka teised Golden Globe filmiauhinna saajad

  1. Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum.

    Science.gov (United States)

    Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C

    2011-05-01

    Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  2. Curvularia microspora sp. nov. associated with leaf diseases of Hippeastrum striatum in China

    Directory of Open Access Journals (Sweden)

    Yin Liang

    2018-01-01

    Full Text Available An undescribed Curvularia sp. was isolated from the leaf spot disease of Barbados Lily (Hippeastrum striatum (Lam. Moore. Phylogenetic analyses of combined ITS, 28S, GPD1 and TEF1 sequence data place nine strains of this species in the trifolii-clade, but they clustered together as an independent lineage with strong support. This species was morphologically compared with related species in the trifolii-clade. Based on differences in morphology and phylogeny, it is concluded that this species is a new taxon, introduced as Curvularia microspora sp. nov. Pathogenicity testing determined the new species to be pathogenic on H. striatum.

  3. Development of beta 1 and beta 2 adrenergic receptors in baboon brain: an autoradiographic study using [125I]iodocyanopindolol

    International Nuclear Information System (INIS)

    Slesinger, P.A.; Lowenstein, P.R.; Singer, H.S.; Walker, L.C.; Casanova, M.F.; Price, D.L.; Coyle, J.T.

    1988-01-01

    [125I]iodocyanopindolol (ICYP) autoradiography was used to investigate the temporal development and distribution of beta 1 and beta 2 receptors in brains of baboons at ages embryonic day 100 (E100), full-term gestation (El80), and 3 years. In all brain regions examined, with the exception of the hippocampus, binding to beta 1 receptors exceeded that to beta 2 receptors. The highest densities of beta 1 receptors were found in the caudate nucleus, putamen, globus pallidus, substantia nigra, and cerebral cortex; intermediate receptor densities were observed in most nuclei of thalamus, and the lowest concentrations were in the hippocampus. At E100, beta receptors were identified in the striatum, globus pallidus, and thalamus. During maturation, the number of beta 1 receptors declined in cortical areas but increased in the head of the caudate and putamen. Significant differences in the developmental distribution of beta receptors during development were also detected: at E100 and E180 beta 1 receptors appeared as patches in the caudate and putamen, but by 3 years of age they were more homogeneously distributed in both regions; changes also occurred in the distribution of binding within cortical layers. Autoradiograms of [125I]ICYP and [3H]mazindol binding show overlapping patches of labeling in the E180 striatum, suggesting a possible developmental association between beta receptors and dopamine high-affinity uptake carrier sites. This study demonstrates that noradrenergic receptors in the primate forebrain undergo significant developmental reorganization with regional variations

  4. Development of beta 1 and beta 2 adrenergic receptors in baboon brain: an autoradiographic study using (/sup 125/I)iodocyanopindolol

    Energy Technology Data Exchange (ETDEWEB)

    Slesinger, P.A.; Lowenstein, P.R.; Singer, H.S.; Walker, L.C.; Casanova, M.F.; Price, D.L.; Coyle, J.T.

    1988-07-15

    (125I)iodocyanopindolol (ICYP) autoradiography was used to investigate the temporal development and distribution of beta 1 and beta 2 receptors in brains of baboons at ages embryonic day 100 (E100), full-term gestation (El80), and 3 years. In all brain regions examined, with the exception of the hippocampus, binding to beta 1 receptors exceeded that to beta 2 receptors. The highest densities of beta 1 receptors were found in the caudate nucleus, putamen, globus pallidus, substantia nigra, and cerebral cortex; intermediate receptor densities were observed in most nuclei of thalamus, and the lowest concentrations were in the hippocampus. At E100, beta receptors were identified in the striatum, globus pallidus, and thalamus. During maturation, the number of beta 1 receptors declined in cortical areas but increased in the head of the caudate and putamen. Significant differences in the developmental distribution of beta receptors during development were also detected: at E100 and E180 beta 1 receptors appeared as patches in the caudate and putamen, but by 3 years of age they were more homogeneously distributed in both regions; changes also occurred in the distribution of binding within cortical layers. Autoradiograms of (125I)ICYP and (3H)mazindol binding show overlapping patches of labeling in the E180 striatum, suggesting a possible developmental association between beta receptors and dopamine high-affinity uptake carrier sites. This study demonstrates that noradrenergic receptors in the primate forebrain undergo significant developmental reorganization with regional variations.

  5. Effects of Bilateral Electrolytic Lesions of the Dorsomedial Striatum on Motor Behavior and Instrumental Learning in Rats

    Directory of Open Access Journals (Sweden)

    Pamphyle Abedi Mukutenga

    2012-08-01

    Full Text Available Introduction: The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum Methods: The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. Results: In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Discussion: Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control.

  6. Brain Magnetic Resonance Imaging in Tyrosinemia

    Energy Technology Data Exchange (ETDEWEB)

    Sener, R.N. [Ege Univ. Hospital, Izmir (Turkey). Dept. of Radiology

    2005-10-01

    A 3.5-year-old girl with tyrosinemia is reported. A computed tomography scan of the abdomen revealed multiple hepatic nodules. Brain magnetic resonance imaging revealed bilateral high-signal changes confined to the globus pallidus on T2-weighted images. Globus pallidus lesions likely represented neuropathologic changes such as astocytosis, delayed myelination, and status spongiosus (myelin splitting and vacuolation)

  7. Brain Magnetic Resonance Imaging in Tyrosinemia

    International Nuclear Information System (INIS)

    Sener, R.N.

    2005-01-01

    A 3.5-year-old girl with tyrosinemia is reported. A computed tomography scan of the abdomen revealed multiple hepatic nodules. Brain magnetic resonance imaging revealed bilateral high-signal changes confined to the globus pallidus on T2-weighted images. Globus pallidus lesions likely represented neuropathologic changes such as astocytosis, delayed myelination, and status spongiosus (myelin splitting and vacuolation)

  8. Human Dorsal Striatum Encodes Prediction Errors during Observational Learning of Instrumental Actions

    Science.gov (United States)

    Cooper, Jeffrey C.; Dunne, Simon; Furey, Teresa; O'Doherty, John P.

    2012-01-01

    The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of…

  9. Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum

    Directory of Open Access Journals (Sweden)

    Haiyan Jiang

    2018-05-01

    Full Text Available The caudal region of the rodent striatum, called the tail of the striatum (TS, is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

  10. Materials as regard about ecology and spreading of lycodine striatum bicolor nik in Tajikistan

    International Nuclear Information System (INIS)

    Sattorov, T.S.; Khidirov, Kh.; Mukhammadkulov, M.

    2003-01-01

    In this article is placed new scientific information about biology, ecology and spreading of Lycodine striatum bicolor within the territory of Tajikistan. Finding available in this article concerning spreading of flus snake are considered to be new. This scarce snake was discovered for the first time in Northern part of Tajikistan. This new information will enrich our notions about Reptile fauna of Tajikistan

  11. Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

    Directory of Open Access Journals (Sweden)

    Kevin D. Alloway

    2017-07-01

    Full Text Available The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD and related neurological disorders.

  12. Stress induces a shift towards striatum-dependent stimulus-response learning via the mineralocorticoid receptor

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernandez, G.

    2017-01-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  13. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernández, G.

    2017-01-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  14. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

    NARCIS (Netherlands)

    Vogel, Susanne; Klumpers, Floris; Schroeder, Tobias Navarro; Oplaat, Krista T.; Krugers, Harm J.; Oitzl, Melly S.; Joels, Marian; Doeller, Christian F.; Fernandez, Guillen

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  15. Hippocampal projections to the ventral striatum: from spatial memory to motivated behavior

    NARCIS (Netherlands)

    van der Meer, M.M.A; Ito, R.; Lansink, C.S.; Pennartz, C.M.A.; Derdikman, D.; Knierim, J.J.

    2014-01-01

    Multiple regions of the hippocampal formation project to the ventral striatum, a central node in brain circuits that subserve aspects of motivation. These projections emphasize information flow from the ventral (temporal) pole of the hippocampus and interact with converging projections and

  16. Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

    Science.gov (United States)

    Baker, Phillip M.; Ragozzino, Michael E.

    2014-01-01

    Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

  17. Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

    NARCIS (Netherlands)

    Holz, N.E.; Boecker-Schlier, R.; Buchmann, A.F.; Blomeyer, D.; Jennen-Steinmetz, C.; Baumeister, S.; Plichta, M.M.; Cattrell, A.; Schumann, G.; Esser, G.; Schmidt, M.; Buitelaar, J.K.; Meyer-Lindenberg, A.; Banaschewski, T.; Brandeis, D.; Laucht, M.

    2017-01-01

    Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At

  18. [Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

    Science.gov (United States)

    Liu, Ping; He, Xinrong; Guo, Mei

    2010-04-01

    To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P Calculus Bovis group was higher than combination group (P Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

  19. A revision of the South American snake genus Thamnodynastes Wagler, 1830 (Serpentes, Colubridae, Tachymenini. I. Two new species of Thamnodynastes from Central Brazil and adjacent areas, with a redefinition of and neotype designation for Thamnodynastes pallidus (Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Joseph R. Bailey

    2005-12-01

    Full Text Available Two new species of Thamnodynastes whose ranges are entirely or largely in Brazil are described. Thamnodynastes pallidus, one of the most easily identified species of the genus, is redefined and a neotype is designated, and Coluber strigilis Thunberg is placed in its synonymy, thus clarifying an enduring state of confusion in the taxonomy of this genus.

  20. The role of the dorsoanterior striatum in implicit motivation: The case of the need for power

    Directory of Open Access Journals (Sweden)

    Oliver C Schultheiss

    2013-04-01

    Full Text Available Implicit motives like the need for power (nPower scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (a enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions in behavioral studies and (b activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka, Nakamura, Sakai, and Nakahara's (2002; Current Opinion in Neurobiology, 12(2, 217-222 model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation.

  1. Fast and robust segmentation of the striatum using deep convolutional neural networks.

    Science.gov (United States)

    Choi, Hongyoon; Jin, Kyong Hwan

    2016-12-01

    Automated segmentation of brain structures is an important task in structural and functional image analysis. We developed a fast and accurate method for the striatum segmentation using deep convolutional neural networks (CNN). T1 magnetic resonance (MR) images were used for our CNN-based segmentation, which require neither image feature extraction nor nonlinear transformation. We employed two serial CNN, Global and Local CNN: The Global CNN determined approximate locations of the striatum. It performed a regression of input MR images fitted to smoothed segmentation maps of the striatum. From the output volume of Global CNN, cropped MR volumes which included the striatum were extracted. The cropped MR volumes and the output volumes of Global CNN were used for inputs of Local CNN. Local CNN predicted the accurate label of all voxels. Segmentation results were compared with a widely used segmentation method, FreeSurfer. Our method showed higher Dice Similarity Coefficient (DSC) (0.893±0.017 vs. 0.786±0.015) and precision score (0.905±0.018 vs. 0.690±0.022) than FreeSurfer-based striatum segmentation (p=0.06). Our approach was also tested using another independent dataset, which showed high DSC (0.826±0.038) comparable with that of FreeSurfer. Comparison with existing method Segmentation performance of our proposed method was comparable with that of FreeSurfer. The running time of our approach was approximately three seconds. We suggested a fast and accurate deep CNN-based segmentation for small brain structures which can be widely applied to brain image analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum.

    Science.gov (United States)

    Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan

    2016-12-14

    Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior. Converging evidence in human neuroimaging studies has shown that the reward prediction errors are correlated with activity in the ventral striatum. Our results demonstrate that this region is simultaneously correlated with a stimulus prediction error. Furthermore, the learning system that is currently dominating behavioral choice dynamically engages the ventral striatum for computing its prediction errors. This demonstrates that the prediction error representations are highly dynamic and influenced by various experimental context. This finding points to a general role of the ventral striatum in detecting expectancy violations and encoding error signals regardless of the specific nature of the reinforcer itself. Copyright © 2016 the authors 0270-6474/16/3612650-11$15.00/0.

  3. Quantitative Imaging of Cholinergic Interneurons Reveals a Distinctive Spatial Organization and a Functional Gradient across the Mouse Striatum.

    Directory of Open Access Journals (Sweden)

    Miriam Matamales

    Full Text Available Information processing in the striatum requires the postsynaptic integration of glutamatergic and dopaminergic signals, which are then relayed to the output nuclei of the basal ganglia to influence behavior. Although cellularly homogeneous in appearance, the striatum contains several rare interneuron populations which tightly modulate striatal function. Of these, cholinergic interneurons (CINs have been recently shown to play a critical role in the control of reward-related learning; however how the striatal cholinergic network is functionally organized at the mesoscopic level and the way this organization influences striatal function remains poorly understood. Here, we systematically mapped and digitally reconstructed the entire ensemble of CINs in the mouse striatum and quantitatively assessed differences in densities, spatial arrangement and neuropil content across striatal functional territories. This approach demonstrated that the rostral portion of the striatum contained a higher concentration of CINs than the caudal striatum and that the cholinergic content in the core of the ventral striatum was significantly lower than in the rest of the regions. Additionally, statistical comparison of spatial point patterns in the striatal cholinergic ensemble revealed that only a minor portion of CINs (17% aggregated into cluster and that they were predominantly organized in a random fashion. Furthermore, we used a fluorescence reporter to estimate the activity of over two thousand CINs in naïve mice and found that there was a decreasing gradient of CIN overall function along the dorsomedial-to-ventrolateral axis, which appeared to be independent of their propensity to aggregate within the striatum. Altogether this work suggests that the regulation of striatal function by acetylcholine across the striatum is highly heterogeneous, and that signals originating in external afferent systems may be principally determining the function of CINs in the

  4. Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

    Directory of Open Access Journals (Sweden)

    Silvana Vargas Superti

    2009-04-01

    Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

  5. SELEKSI RUMPUT LAUT Kappaphycus striatum DALAM UPAYA PENINGKATAN LAJU PERTUMBUHAN BIBIT UNTUK BUDIDAYA

    Directory of Open Access Journals (Sweden)

    Andi Parenrengi

    2017-01-01

    Full Text Available Budidaya rumput laut di Indonesia semakin berkembang seiring dengan peningkatan permintaan bahan baku industri untuk pasar domestik dan eksport. Rumput laut Kappaphycus striatum, salah satu spesies rumput laut komersil, telah intensif dibudidayakan di perairan pantai. Saat ini, masalah utama yang dihadapi pembudidaya adalah rendahnya kualitas bibit yang berasal dari hasil budidaya. Seleksi varietas merupakan salah satu metode yang diharapkan dapat meningkatkan laju pertumbuhan rumput laut. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh seleksi varietas terhadap pertumbuhan rumput laut sehingga dapat dilakukan produksi bibit unggul untuk keperluan budidaya. Budidaya rumput laut K. striatum telah dilakukan di Teluk Laikang, Kabupaten Takalar, Provinsi Sulawesi Selatan dengan menggunakan metode long line. Seleksi varietas dilakukan berdasarkan parameter laju pertumbuhan harian (LPH dan metode seleksi mengacu pada protokol seleksi yang telah dikembangkan pada rumput laut K. alvarezii. Hasil penelitian menunjukkan bahwa LPH bibit hasil seleksi lebih tinggi (P

  6. Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq

    Directory of Open Access Journals (Sweden)

    Ozgun Gokce

    2016-07-01

    Full Text Available The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed ten differentiated, distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSNs that have specific markers and that overexpress genes linked to cognitive disorders and addiction. We also describe continuous cellular identities, which increase heterogeneity within discrete cell types. Finally, we identified cell type-specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns. Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states.

  7. Isolation and characterization of neural stem cells from human fetal striatum

    International Nuclear Information System (INIS)

    Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

    2005-01-01

    This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

  8. Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

    Directory of Open Access Journals (Sweden)

    Paola Fuentes-Claramonte

    Full Text Available Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

  9. Existence and control of Go/No-Go decision transition threshold in the striatum.

    Directory of Open Access Journals (Sweden)

    Jyotika Bahuguna

    2015-04-01

    Full Text Available A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

  10. Striatum morphometry is associated with cognitive control deficits and symptom severity in internet gaming disorder.

    Science.gov (United States)

    Cai, Chenxi; Yuan, Kai; Yin, Junsen; Feng, Dan; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Jin, Chenwang; Qin, Wei; Tian, Jie

    2016-03-01

    Internet gaming disorder (IGD), identified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Section III as a condition warranting more clinical research, may be associated with impaired cognitive control. Previous IGD-related studies had revealed structural abnormalities in the prefrontal cortex, an important part of prefrontal-striatal circuits, which play critical roles in cognitive control. However, little is known about the relationship between the striatal nuclei (caudate, putamen, and nucleus accumbens) volumes and cognitive control deficit in individuals with IGD. Twenty-seven adolescents with IGD and 30 age-, gender- and education-matched healthy controls participated in this study. The volume differences of the striatum were assessed by measuring subcortical volume in FreeSurfer. Meanwhile, the Stroop task was used to detect cognitive control deficits. Correlation analysis was used to investigate the relationship between striatal volumes and performance in the Stroop task as well as severity in IGD. Relative to controls, the IGD committed more incongruent condition response errors during the Stroop task and showed increased volumes of dorsal striatum (caudate) and ventral striatum (nucleus accumbens). In addition, caudate volume was correlated with Stroop task performance and nucleus accumbens (NAc) volume was associated with the internet addiction test (IAT) score in the IGD group. The increased volumes of the right caudate and NAc and their association with behavioral characteristics (i.e., cognitive control and severity) in IGD were detected in the present study. Our findings suggest that the striatum may be implicated in the underlying pathophysiology of IGD.

  11. Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

    2004-01-01

    Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2→3.9%, CA: 57.4→14.1%, ST: 17.7→0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction

  12. Evidence that Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    OpenAIRE

    Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Logan, Jean; Benveniste, Helene; Kim, Ron; Thanos, Panayotis K.; Ferré, Sergi

    2012-01-01

    Dopamine D2 receptors are involved with wakefulness but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [11C]raclopride in controls) in striatum, but could not determine if this reflected dopamine increases ([11C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases in...

  13. Distribution of GABAergic interneurons and dopaminergic cells in the functional territories of the human striatum.

    Science.gov (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2012-01-01

    The afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. Among them, GABAergic interneurons are the most abundant, and can be sorted in three populations according to their content in the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin (CB). Conversely, striatal dopaminergic cells (whose role as interneurons is still unclear) are scarce. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment. We used immunohistochemical methods to visualize CR, PV, CB and tyrosine hydroxylase (TH) positive striatal neurons. The interneuronal distribution was assessed by stereological methods applied to every striatal functional territory. Considering the four cell groups altogether, their density was higher in the associative (2120±91 cells/mm(3)) than in the sensorimotor (959±47 cells/mm(3)) or limbic (633±119 cells/mm(3)) territories. CB- and TH-immunoreactive(-ir) cells were distributed rather homogeneously in the three striatal territories. However, the density of CR and PV interneurons were more abundant in the associative and sensorimotor striatum, respectively. Regarding to their compartmental organization, CR-ir interneurons were frequently found in the border between compartments in the associative and sensorimotor territories, and CB-ir interneurons abounded at the striosome/matrix border in the sensorimotor domain. The present study demonstrates that the architecture of the human striatum in terms of its interneuron composition varies in its three functional territories. Furthermore, our data highlight the importance of CR-ir striatal interneurons in the integration of associative information, and the selective role of PV-ir interneurons in

  14. Effect of electrolytic lesion of the dorsomedial striatum on sexual behaviour and locomotor activity in rats.

    Science.gov (United States)

    Ortiz-Pulido, R; Hernández-Briones, Z S; Tamariz-Rodríguez, A; Hernández, M E; Aranda-Abreu, G E; Coria-Avila, G A; Manzo, J; García, L I

    2017-06-01

    Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behaviour. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals.

    Science.gov (United States)

    Hwang, J W; Xin, S C; Ou, Y M; Zhang, W Y; Liang, Y L; Chen, J; Yang, X Q; Chen, X Y; Guo, T W; Yang, X J; Ma, W H; Li, J; Zhao, B C; Tu, Y; Kong, J

    2016-05-01

    Subthreshold depression (StD) is a highly prevalent condition associated with increased service utilization and social morbidity. Nevertheless, due to limitations in current diagnostic systems that set the boundary for major depressive disorder (MDD), very few brain imaging studies on the neurobiology of StD have been carried out, and its underlying neurobiological mechanism remains unclear. In recent years, accumulating evidence suggests that the disruption of the default mode network (DMN), a network involved in self-referential processing, affective cognition, and emotion regulation, is involved in major depressive disorder. Using independent component analysis, we investigated resting-state default mode network (DMN) functional connectivity (FC) changes in two cohorts of StD patients with different age ranges (young and middle-aged, n = 57) as well as matched controls (n = 79). We found significant FC increase between the DMN and ventral striatum (key region in the reward network), in both cohorts of StD patients in comparison with controls. In addition, we also found the FC between the DMN and ventral striatum was positively and significantly associated with scores on the Center for Epidemiologic Studies Depression Scale (CES-D), a measurement of depressive symptomatology. We speculate that this enhanced FC between the DMN and the ventral striatum may reflect a self-compensation to ameliorate the lowered reward function. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.

    Science.gov (United States)

    Xue, Bing; Chen, Elton C; He, Nan; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

    2017-01-01

    Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs. In addition, D1R and D2R coactivation recruited GluA1 and PKA preferentially to extrasynaptic sites. In sum, our in vivo data support an existence of a dynamic DA-ACh balance in the striatum which actively modulates GluA1 AMPAR phosphorylation and trafficking. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward.

    Science.gov (United States)

    Kishida, Kenneth T; Saez, Ignacio; Lohrenz, Terry; Witcher, Mark R; Laxton, Adrian W; Tatter, Stephen B; White, Jason P; Ellis, Thomas L; Phillips, Paul E M; Montague, P Read

    2016-01-05

    In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson's disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson's disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons.

  18. Characteristics of fast-spiking neurons in the striatum of behaving monkeys.

    Science.gov (United States)

    Yamada, Hiroshi; Inokawa, Hitoshi; Hori, Yukiko; Pan, Xiaochuan; Matsuzaki, Ryuichi; Nakamura, Kae; Samejima, Kazuyuki; Shidara, Munetaka; Kimura, Minoru; Sakagami, Masamichi; Minamimoto, Takafumi

    2016-04-01

    Inhibitory interneurons are the fundamental constituents of neural circuits that organize network outputs. The striatum as part of the basal ganglia is involved in reward-directed behaviors. However, the role of the inhibitory interneurons in this process remains unclear, especially in behaving monkeys. We recorded the striatal single neuron activity while monkeys performed reward-directed hand or eye movements. Presumed parvalbumin-containing GABAergic interneurons (fast-spiking neurons, FSNs) were identified based on narrow spike shapes in three independent experiments, though they were a small population (4.2%, 42/997). We found that FSNs are characterized by high-frequency and less-bursty discharges, which are distinct from the basic firing properties of the presumed projection neurons (phasically active neurons, PANs). Besides, the encoded information regarding actions and outcomes was similar between FSNs and PANs in terms of proportion of neurons, but the discharge selectivity was higher in PANs than that of FSNs. The coding of actions and outcomes in FSNs and PANs was consistently observed under various behavioral contexts in distinct parts of the striatum (caudate nucleus, putamen, and anterior striatum). Our results suggest that FSNs may enhance the discharge selectivity of postsynaptic output neurons (PANs) in encoding crucial variables for a reward-directed behavior. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward

    Science.gov (United States)

    Kishida, Kenneth T.; Saez, Ignacio; Lohrenz, Terry; Witcher, Mark R.; Laxton, Adrian W.; Tatter, Stephen B.; White, Jason P.; Ellis, Thomas L.; Phillips, Paul E. M.; Montague, P. Read

    2016-01-01

    In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson’s disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’s disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons. PMID:26598677

  20. Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum

    Science.gov (United States)

    Salinas, Armando G.; Davis, Margaret I.; Lovinger, David M.; Mateo, Yolanda

    2016-01-01

    The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson’s disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix. PMID:27036891

  1. SSRI antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum

    Science.gov (United States)

    Van Waes, Vincent; Beverley, Joel; Marinelli, Michela; Steiner, Heinz

    2010-01-01

    The psychostimulant methylphenidate (Ritalin) is used in conjunction with selective serotonin reuptake inhibitors (SSRIs) in the treatment of medical conditions such as attention-deficit hyperactivity disorder with anxiety/depression comorbidity and major depression. Co-exposure also occurs in patients on SSRIs that use psychostimulant “cognitive enhancers”. Methylphenidate is a dopamine/norepinephrine reuptake inhibitor that produces altered gene expression in the forebrain; these effects partly mimic gene regulation by cocaine (dopamine/norepinephrine/serotonin reuptake inhibitor). We investigated whether the addition of SSRIs (fluoxetine or citalopram; 5 mg/kg) modified gene regulation by methylphenidate (2–5 mg/kg) in the striatum and cortex of adolescent rats. Our results show that SSRIs potentiate methylphenidate-induced expression of the transcription factors zif 268 and c-fos in the striatum, rendering these molecular changes more cocaine-like. Present throughout most of the striatum, this potentiation was most robust in its sensorimotor parts. The methylphenidate + SSRI combination also enhanced behavioral stereotypies, consistent with dysfunction in sensorimotor striatal circuits. In so far as such gene regulation is implicated in psychostimulant addiction, our findings suggest that SSRIs may enhance the addiction liability of methylphenidate. PMID:20704593

  2. Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum.

    Science.gov (United States)

    Van Waes, Vincent; Beverley, Joel; Marinelli, Michela; Steiner, Heinz

    2010-08-01

    The psychostimulant methylphenidate (Ritalin) is used in conjunction with selective serotonin reuptake inhibitors (SSRIs) in the treatment of medical conditions such as attention-deficit hyperactivity disorder with anxiety/depression comorbidity and major depression. Co-exposure also occurs in patients on SSRIs who use psychostimulant 'cognitive enhancers'. Methylphenidate is a dopamine/norepinephrine reuptake inhibitor that produces altered gene expression in the forebrain; these effects partly mimic gene regulation by cocaine (dopamine/norepinephrine/serotonin reuptake inhibitor). We investigated whether the addition of SSRIs (fluoxetine or citalopram; 5 mg/kg) modified gene regulation by methylphenidate (2-5 mg/kg) in the striatum and cortex of adolescent rats. Our results show that SSRIs potentiate methylphenidate-induced expression of the transcription factor genes zif268 and c-fos in the striatum, rendering these molecular changes more cocaine-like. Present throughout most of the striatum, this potentiation was most robust in its sensorimotor parts. The methylphenidate + SSRI combination also enhanced behavioral stereotypies, consistent with dysfunction in sensorimotor striatal circuits. In so far as such gene regulation is implicated in psychostimulant addiction, our findings suggest that SSRIs may enhance the addiction potential of methylphenidate.

  3. Re-thinking the role of the dorsal striatum in egocentric/response strategy

    Directory of Open Access Journals (Sweden)

    Fanny BOTREAU

    2010-02-01

    Full Text Available Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

  4. Decreased rates of terpene emissions in Ornithopus compressus L. and Trifolium striatum L. by ozone exposure and nitrogen fertilization.

    Science.gov (United States)

    Llusia, Joan; Bermejo-Bermejo, Victoria; Calvete-Sogo, Héctor; Peñuelas, Josep

    2014-11-01

    Increasing tropospheric ozone (O3) and nitrogen soil availability (N) are two of the main drivers of global change. They both may affect gas exchange, including plant emission of volatiles such as terpenes. We conducted an experiment using open-top chambers to analyze these possible effects on two leguminous species of Mediterranean pastures that are known to have different O3 sensitivity, Ornithopus compressus and Trifolium striatum. O3 exposure and N fertilization did not affect the photosynthetic rates of O. compressus and T. striatum, although O3 tended to induce an increase in the stomatal conductance of both species, especially T. striatum, the most sensitive species. O3 and N soil availability reduced the emission of terpenes in O. compressus and T. striatum. If these responses are confirmed as a general pattern, O3 could affect the competitiveness of these species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. A molecular approach towards the taxonomy of fresh water prawns Macrobrachium striatum and M. equidens (Decapoda, Palaemonidae) using mitochondrial markers.

    Science.gov (United States)

    Jose, Deepak; Nidhin, B; Anil Kumar, K P; Pradeep, P J; Harikrishnan, M

    2016-07-01

    Genus Macrobrachium includes freshwater prawns which inhabit most diverse habitats ranging from low saline areas to inland hill streams and impounded water bodies. Being morphologically conserved, this genus has been exposed to severe disputes related to their taxonomy, systematics and phylogeny. Macrobrachium striatum and M. equidens represent two morphologically related congeneric species within this genus. Earlier, M. striatum was considered as a striped form of M. equidens. Though these species are now well-described morphologically and differentiated into two species, no molecular level investigation has been carried out in support of their speciation. We report a study on M. striatum and M. equidens with emphasis to their molecular data through mitochondrial markers (16S ribosomal RNA and cytochrome oxidase subunit I). Results obtained from developed molecular markers of the two species revealed considerable genetic differentiation between them. Phylogram generated using Minimum evolution and Neighbour joining analyses differentiated M. striatum and M. equidens as two independent species. Genetic distance data showed high interspecific divergence (ranging from 3.9% to 17.0% for 16S rRNA sequences and 13.8% to 21.0% for COI sequences) between M. striatum and M. equidens confirming the findings of phylogram. Hence, it could be delineated that M. striatum and M. equidens represent two distinct species within genus Macrobrachium with emphasis to their morphology and genetics.

  6. Biochemical and microbiological evidence for fermentative digestion in free-living land iguanas (Conolophus pallidus) and marine iguanas (Amblyrhynchus cristatus) on the Galápagos archipelago.

    Science.gov (United States)

    Mackie, Roderick I; Rycyk, Mathew; Ruemmler, Rebecca L; Aminov, Rustam I; Wikelski, Martin

    2004-01-01

    Herbivorous lizards are potentially capable of high digestive efficiency, but the presence of an indigenous microbial population has been implied from measurements of activity rather than directly studied. This study is the first to provide direct biochemical and microbiological evidence for fermentative digestion in free-living land iguanas (Conolophus pallidus) and marine iguanas (Amblyrhynchus cristatus) from the Galapagos archipelago. In marine iguanas, the stomach and large capacious colon contained ca. 32% and 60%, respectively, of the weight of total gut content. Total volatile fatty acid concentration was ca. 150 and 180 mM, respectively, for marine and land iguanas. Molar proportions of acetate, propionate, and butyrate (80.3%, 9.5%, and 3.5%) in land iguana fecal samples were similar to those for marine iguanas. Examination of fecal samples using confocal and transmission electron microscopy, as well as cultivable counts, revealed a dense and diverse population of bacteria, with spores prominent. Total culturable counts of anaerobes (2.22x10(8) g(-1) wet weight of fecal material) outnumbered aerobes on average by a factor of ca. 700. Combined, these results strongly support the contention that these unique herbivorous lizards are largely dependent on the presence and metabolic activities of a resident bacterial population in order to hydrolyze and ferment plant polymers that are indigestible to the host.

  7. Utility of thermo-alkali-stable γ-CA from polyextremophilic bacterium Aeribacillus pallidus TSHB1 in biomimetic sequestration of CO2 and as a virtual peroxidase.

    Science.gov (United States)

    Bose, Himadri; Satyanarayana, Tulasi

    2017-04-01

    Aeribacillus pallidus TSHB1 polyextremophilic bacterium produces a γ-carbonic anhydrase (ApCA), which is a homotrimeric biocatalyst with a subunit molecular mass of 32 ± 2 kDa. The enzyme is stable in the pH range between 8.0 and 11.0 and thus alkali-stable and moderately thermostable with T 1/2 values of 40 ± 1, 15 ± 1, and 8 ± 0.5 min at 60, 70, and 80 °C, respectively. Activation energy for irreversible inactivation "E d " of carbonic anhydrase is 67.119 kJ mol -1 . The enzyme is stable in the presence of various flue gas contaminants such as SO 3 2- ,SO 4 2- , and NO 3 - and cations Mg 2+ , Mn 2+ , Ca 2+ , and Ba 2+ . Fluorescence studies in the presence of N-bromosuccinimide and fluorescence quenching using KI and acrylamide revealed the importance of tryptophan residues in maintaining the structural integrity of the enzyme. ApCA is more efficient than the commercially available bovine carbonic anhydrase (BCA) in CO 2 sequestration. The enzyme was successfully used in biomineralization of CO 2 from flue gas. Replacement of active site Zn 2+ with Mn 2+ enabled ApCA to function as a peroxidase which exhibited alkali-stability and moderate thermostability like ApCA.

  8. Purification and biochemical characterization of a novel thermostable serine alkaline protease from Aeribacillus pallidus C10: a potential additive for detergents.

    Science.gov (United States)

    Yildirim, Vildan; Baltaci, Mustafa Ozkan; Ozgencli, Ilknur; Sisecioglu, Melda; Adiguzel, Ahmet; Adiguzel, Gulsah

    2017-12-01

    An extracellular thermostable alkaline serine protease enzyme from Aeribacillus pallidus C10 (GenBank No: KC333049), was purified 4.85 and 17. 32-fold with a yield of 26.9 and 19.56%, respectively, through DE52 anion exchange and Probond affinity chromatography. The molecular mass of the enzyme was determined through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), with approximately 38.35 kDa. The enzyme exhibited optimum activity at pH 9 and at temperature 60 °C. It was determined that the enzyme had remained stable at the range of pH 7.0-10.0, and that it had preserved more than 80% of its activity at a broad temperature range (20-80 °C). The enzyme activity was found to retain more than 70% and 55% in the presence of organic solvents and commercial detergents, respectively. In addition, it was observed that the enzyme activity had increased in the presence of 5% SDS. K M and V max values were calculated as 0.197 mg/mL and 7.29 μmol.mL - 1 .min - 1 , respectively.

  9. Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

    International Nuclear Information System (INIS)

    Kienast, Thorsten; Rapp, Michael; Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias; Wrase, Jana; Heinz, Andreas; Braus, Dieter F.; Smolka, Michael N.; Mann, Karl; Roesch, Frank; Cumming, Paul; Gruender, Gerhard; Bartenstein, Peter

    2008-01-01

    Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [ 18 F]DOPA for measurements of dopamine synthesis capacity and [ 18 F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [ 18 F]DOPA net influx constant K in app /[ 18 F]DMFP-binding potential (BP N D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

  10. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  11. Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

    Science.gov (United States)

    Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Mannisto, P. T.

    1992-01-01

    Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 micrograms/ml, or about 2% of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5% and 1.5%, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33% and 16%, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceeding 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

  12. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi, F.

    2012-01-01

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11 C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11 C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11 C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  13. Monitoring extracellular pH, oxygen, and dopamine during reward delivery in the striatum of primates.

    Science.gov (United States)

    Ariansen, Jennifer L; Heien, Michael L A V; Hermans, Andre; Phillips, Paul E M; Hernadi, Istvan; Bermudez, Maria A; Schultz, Wolfram; Wightman, R Mark

    2012-01-01

    Dopamine projections that extend from the ventral tegmental area to the striatum have been implicated in the biological basis for behaviors associated with reward and addiction. Until recently, it has been difficult to evaluate the complex balance of energy utilization and neural activity in the striatum. Many techniques such as electrophysiology, functional magnetic resonance imaging (fMRI), and fast-scan cyclic voltammetry have been employed to monitor these neurochemical and neurophysiological changes. In this brain region, physiological responses to cues and rewards cause local, transient pH changes. Oxygen and pH are coupled in the brain through a complex system of blood flow and metabolism as a result of transient neural activity. Indeed, this balance is at the heart of imaging studies such as fMRI. To this end, we measured pH and O(2) changes with fast-scan cyclic voltammetry in the striatum as indices of changes in metabolism and blood flow in vivo in three Macaca mulatta monkeys during reward-based behaviors. Specifically, the animals were presented with Pavlovian conditioned cues that predicted different probabilities of liquid reward. They also received free reward without predictive cues. The primary detected change consisted of pH shifts in the striatal extracellular environment following the reward predicting cues or the free reward. We observed three types of cue responses that consisted of purely basic pH shifts, basic pH shifts followed by acidic pH shifts, and purely acidic pH shifts. These responses increased with reward probability, but were not significantly different from each other. The pH changes were accompanied by increases in extracellular O(2). The changes in pH and extracellular O(2) are consistent with current theories of metabolism and blood flow. However, they were of sufficient magnitude that they masked dopamine changes in the majority of cases. The findings suggest a role of these chemical responses in neuronal reward processing.

  14. Atypical and typical neuroleptic treatments induce distinct programs of transcription factor expression in the striatum.

    Science.gov (United States)

    Hiroi, N; Graybiel, A M

    1996-10-07

    Atypical and typical neuroleptics, when administered chronically, can bring about profound but contrasting changes in schizophrenic symptoms and motor activation and dramatically modulate brain neurochemistry. To explore the transcriptional events that might be involved in this neurochemical regulation, we used immunohistochemistry and immunoblotting to examine the expression patterns of two bZip transcription factors, c-Fos and FosB, in the striatum of rats treated acutely and chronically with neuroleptic drugs of different classes. Typical and atypical neuroleptic drugs produced contrasting regulatory effects on a FosB-like protein of ca. 36-39 kDa, the molecular weight of truncated FosB (delta FosB). Chronic treatments with two typical neuroleptics, haloperidol and metoclopramide, but not with the atypical neuroleptic clozapine, led to markedly enhanced FosB-like immunoreactivity in the caudoputamen. Further, c-Fos-like protein in the striatum, considered a marker for the induction of antipsychotic actions by neuroleptic treatments, was downregulated by chronic treatment with the two potent antipsychotic drugs tested, but not by chronic treatment with metoclopramide, which has low antipsychotic efficacy but induces extrapyramidal side effects. These results suggest that chronic treatments with neuroleptics having different effects on cognitive and motor behavior induce different long-term changes in transcription factor expression in the striatum. Nevertheless, we found that neuroleptics of both classes regulated transcription factor expression in overlapping populations of striatal neurons expressing enkephalin or DARPP-32. Contrasting patterns of transcriptional regulation in these neurons may thus contribute to the distinct neurochemical and behavioral effects that characterize neuroleptics of different classes.

  15. Differential effect of quetiapine and lithium on functional connectivity of the striatum in first episode mania.

    Science.gov (United States)

    Dandash, Orwa; Yücel, Murat; Daglas, Rothanthi; Pantelis, Christos; McGorry, Patrick; Berk, Michael; Fornito, Alex

    2018-03-06

    Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months. Resting-state fMRI was acquired at baseline, 3 months (patient only) and 12 months. The effects of treatment group, time and their interaction, on striatal functional connectivity were assessed using voxel-wise general linear modelling. At baseline, FEM patients showed reduced connectivity in the dorsal (p = 0.05) and caudal (p = 0.008) cortico-striatal systems when compared to healthy controls at baseline. FEM patients also showed increased connectivity in a circuit linking the ventral striatum with the medial orbitofrontal cortex, cerebellum and thalamus (p = 0.02). Longitudinally, we found a significant interaction between time and treatment group, such that lithium was more rapid, compared to quetiapine, in normalizing abnormally increased functional connectivity, as assessed at 3-month and 12-month follow-ups. The results suggest that FEM is associated with reduced connectivity in dorsal and caudal corticostriatal systems, as well as increased functional connectivity of ventral striatal systems. Lithium appears to act more rapidly than quetiapine in normalizing hyperconnectivity of the ventral striatum with the cerebellum. The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12607000639426). http://www.anzctr.org.au.

  16. Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S; Logan, Jean; Benveniste, Helene; Kim, Ron; Thanos, Panayotis K; Ferré, Sergi

    2012-05-09

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [(11)C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([(11)C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [(11)C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  17. Functional interactions between dentate gyrus, striatum and anterior thalamic nuclei on spatial memory retrieval.

    Science.gov (United States)

    Méndez-Couz, M; Conejo, N M; González-Pardo, H; Arias, J L

    2015-04-24

    The standard model of memory system consolidation supports the temporal reorganization of brain circuits underlying long-term memory storage, including interactions between the dorsal hippocampus and extra-hippocampal structures. In addition, several brain regions have been suggested to be involved in the retrieval of spatial memory. In particular, several authors reported a possible role of the ventral portion of the hippocampus together with the thalamus or the striatum in the persistence of this type of memory. Accordingly, the present study aimed to evaluate the contribution of different cortical and subcortical brain regions, and neural networks involved in spatial memory retrieval. For this purpose, we used cytochrome c oxidase quantitative histochemistry as a reliable method to measure brain oxidative metabolism. Animals were trained in a hidden platform task and tested for memory retention immediately after the last training session; one week after completing the task, they were also tested in a memory retrieval probe. Results showed that retrieval of the previously learned task was associated with increased levels of oxidative metabolism in the prefrontal cortex, the dorsal and ventral striatum, the anterodorsal thalamic nucleus and the dentate gyrus of the dorsal and ventral hippocampus. The analysis of functional interactions between brain regions suggest that the dorsal and ventral dentate gyrus could be involved in spatial memory retrieval. In addition, the results highlight the key role of the extended hippocampal system, thalamus and striatum in this process. Our study agrees with previous ones reporting interactions between the dorsal hippocampus and the prefrontal cortex during spatial memory retrieval. Furthermore, novel activation patterns of brain networks involving the aforementioned regions were found. These functional brain networks could underlie spatial memory retrieval evaluated in the Morris water maze task. Copyright © 2015 Elsevier B

  18. Morphological features of neurons containing calcium-binding proteins in the human striatum.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A

    1998-01-26

    An immunohistochemical approach was used to characterize the morphological phenotype of neurons containing the calcium-binding proteins calretinin (CR), parvalbumin (PV), or calbindin-D28k (CB) in the normal human striatum. The protein CR occurs in at least four morphologically distinct types of neurons. Apart from the numerous medium-sized aspiny interneurons and the less abundant giant aspiny interneurons, CR also labels some medium-sized spiny neurons morphologically identical to striatal projection neurons. This finding indicates that CR is not only confined to striatal interneurons but also may be involved in the function of certain projection neurons. Some small and peculiar bushy-like aspiny neurons also are enriched with CR. These neurons could correspond to the dwarf or neurogliform neurons first described by Ramón y Cajal (1911). Three types of PV-immunoreactive striatal neurons can be visualized in the human striatum: 1) the common medium-sized aspiny leptodendritic neurons, 2) some smaller and profusely arborized aspiny neurons, and 3) a few large and intensely stained neurons with conspicuously beaded and poorly branched dendrites. The protein CB labels virtually all medium-sized spiny projection neurons located in the striatal matrix but also identifies a small subset of large and more intensely immunostained aspiny neurons. The latter finding indicates that CB is not entirely confined to striatal projection neurons but also may play a role in local circuit neurons. These normative data should help our understanding of the chemical anatomy of the human striatum in both health and disease.

  19. Chemical anatomy of the human ventral striatum and adjacent basal forebrain structures.

    Science.gov (United States)

    Prensa, Lucía; Richard, Sandra; Parent, André

    2003-06-02

    Calbindin D-28k (CB), calretinin (CR), substance P (SP), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) were used as chemical markers to investigate the organization of the ventral striatum (VST) and adjacent structures in healthy human individuals. No clear boundary could be established between the dorsal striatum and the VST, and the core/shell subdivisions of nucleus accumbens (Acb) could be distinguished only at the midrostrocaudal level of the VST. The CB-poor shell displayed intense immunostaining for SP and CR but only weak staining for LAMP. By contrast, the core was weakly stained for SP and CR and moderately stained for LAMP and CB. There was no difference between shell and core with regard to the cholinergic markers. The Acb harbored numerous ChAT- and CR-immunoreactive cell bodies, the latter being distributed according to a marked, mediolaterally increasing gradient. The size of the ChAT- and CR-immunoreactive perikarya in the Acb varied according to their location in the core and shell. The VST was surrounded by a chemically heterogeneous group of cell clusters referred to as interface islands. The CR-rich caudal portion of the VST merged with the bed nucleus of the stria terminalis dorsally and the diagonal band of Broca ventromedially, the latter two structures displaying complex immunostaining patterns. The claustrum was markedly enriched in LAMP and harbored different types of CR- and CB-immunopositive neurons. These results demonstrate that the neurochemical organization of the human VST is strikingly complex and exhibits a greater heterogeneity than the dorsal striatum. Copyright 2003 Wiley-Liss, Inc.

  20. Caffeine stimulates cytochrome oxidase expression and activity in the striatum in a sexually dimorphic manner.

    Science.gov (United States)

    Jones, Frederick S; Jing, Jie; Stonehouse, Anthony H; Stevens, Anthony; Edelman, Gerald M

    2008-09-01

    Epidemiological studies indicate that caffeine consumption reduces the risk of Parkinson's disease (PD) in men, and antagonists of the adenosine 2A receptor ameliorate the motor symptoms of PD. These findings motivated us to identify proteins whose expression is regulated by caffeine in a sexually dimorphic manner. Using mass spectroscopy, we found that Cox7c, a nuclear-encoded subunit of the mitochondrial enzyme cytochrome oxidase, is up-regulated in the striatum of male but not female mice after receiving a single dose of caffeine. The expression of two other Cox subunits, Cox1 and Cox4, was also stimulated by caffeine in a male-specific fashion. This up-regulation of Cox subunits by caffeine was accompanied by an increase in Cox enzyme activity in the male striatum. Caffeine-induced stimulation of Cox expression and activity were reproduced using the adenosine 2A receptor (A2AR)-specific antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-epsilon]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261), and coadministration of the A2AR-specific agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) counteracted the elevation of Cox expression and activity by caffeine. Caffeine also increased Cox activity in PC-12 cells. In contrast, small interfering RNA (siRNA) knockdown of Cox7c expression in PC-12 cells blunted Cox activity, and this was counteracted by caffeine treatment. Caffeine was also found to increase Cox7c mRNA expression in the striatum and in PC-12 cells. This occurred at the level of transcription and was mediated by a segment of the Cox7c promoter. Overall, these findings indicate that cytochrome oxidase is a metabolic target of caffeine and that stimulation of Cox activity by caffeine via blockade of A2AR signaling may be an important mechanism underlying the therapeutic benefits of caffeine in PD.

  1. Separate populations of neurons in ventral striatum encode value and motivation.

    Science.gov (United States)

    Bissonette, Gregory B; Burton, Amanda C; Gentry, Ronny N; Goldstein, Brandon L; Hearn, Taylor N; Barnett, Brian R; Kashtelyan, Vadim; Roesch, Matthew R

    2013-01-01

    Neurons in the ventral striatum (VS) fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.

  2. Identification of Functional Clusters in the Striatum Using Infinite Relational Modeling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther; Madsen, Kristoffer Hougaard; Siebner, Hartwig

    2011-01-01

    In this paper we investigate how the Infinite Relational Model can be used to infer functional groupings of the human striatum using resting state fMRI data from 30 healthy subjects. The Infinite Relational Model is a non-parametric Bayesian method for infering community structure in complex...... are involved in the same neural computations. The reproducibility of the groupings found are assessed by calculating mutual information between half splits of the subject sample for various hyperparameter values. Finally, the model's ability to predict unobserved links is assessed by randomly treating links...

  3. Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seeking

    DEFF Research Database (Denmark)

    Gjedde, Albert; Kumakura, Yoshitaka; Cumming, Paul

    2010-01-01

    Sensation seeking is a core personality trait that declines with age in both men and women, as do also both density and availability of the dopamine D(2/3) receptors in striatum and cortical regions. In contrast, novelty seeking at a given age relates inversely to dopamine receptor availability...... to dopamine concentrations. Higher dopamine occupancy and dopamine concentrations explain the motivation that drives afflicted individuals to seek sensations, in agreement with reduced protection against addictive behavior that is characteristic of individuals with low binding potentials....

  4. Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats.

    Directory of Open Access Journals (Sweden)

    Gabriela P Chaves-Kirsten

    Full Text Available The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson's Disease (PD. Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP, internal globus pallidus (IGP and substantia nigra pars reticulata (SNpr of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH, parvalbumin, calbindin and glutamic acid decarboxylase (GAD expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model.

  5. Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model.

    Science.gov (United States)

    Lu, Yi; Zhang, Xiaoxia; Zhao, Liangcai; Yang, Changwei; Pan, Linlin; Li, Chen; Liu, Kun; Bai, Guanghui; Gao, Hongchang; Yan, Zhihan

    2018-01-01

    Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD), while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo 1 H nuclear magnetic resonance (NMR) spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN) of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu) in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA) increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI) and taurine (Tau) were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

  6. Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact.

    Science.gov (United States)

    Spampinato, U; Esposito, E; Samanin, R

    1985-09-01

    The effects of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and m-chlorophenylpiperazine (CPP), two 5-hydroxytryptamine (5-HT, serotonin) agonists, on the accumulation of 3,4-dihydroxyphenylalanine (DOPA] were studied in the striatum of rats treated with gamma-butyrolactone (GBL). Unlike 2 mg/kg i.p. apomorphine, neither 5 mg/kg i.p. 5-MeO-DMT nor 2.5 mg/kg i.p. CPP significantly reduced the GBL-induced increase in DOPA accumulation in the striatum. 5-MeO-DMT and CPP significantly reduced DOPA accumulation in animals that had received the aromatic amino acid decarboxylase inhibitor Ro 4-4602 but not GBL. 5-HT (10 micrograms in 0.5 microliter) injected in the substantia nigra, pars compacta, like GBL, significantly increased Ro 4-4602-induced accumulation of DOPA in the striatum. The data indicate that 5-HT agonists can reduce 3,4-dihydroxyphenylethylamine (DA, dopamine) synthesis in the striatum of rats only when the impulse flow of DA neurons is intact. An indirect effect through mechanisms controlling DA synthesis in the striatum, for instance cholinergic and GABA-ergic neurons, is suggested.

  7. Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

    Science.gov (United States)

    Mattfeld, Aaron T.; Stark, Craig E. L.

    2015-01-01

    The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. PMID:25560298

  8. Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

    Science.gov (United States)

    Aravamuthan, Bhooma R; Waugh, Jeff L

    2016-01-01

    Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain

  9. Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner.

    Science.gov (United States)

    Ketzef, Maya; Spigolon, Giada; Johansson, Yvonne; Bonito-Oliva, Alessandra; Fisone, Gilberto; Silberberg, Gilad

    2017-05-17

    Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic innervation, particularly to the striatum. PD patients often exhibit sensory impairments, yet the underlying network mechanisms are unknown. Here we examined how dopamine (DA) depletion affects sensory processing in the mouse striatum. We used the optopatcher for online identification of direct and indirect pathway projection neurons (MSNs) during in vivo whole-cell recordings. In control mice, MSNs encoded the laterality of sensory inputs with larger and earlier responses to contralateral than ipsilateral whisker deflection. This laterality coding was lost in DA-depleted mice due to adaptive changes in the intrinsic and synaptic properties, mainly, of direct pathway MSNs. L-DOPA treatment restored laterality coding by increasing the separation between ipsilateral and contralateral responses. Our results show that DA depletion impairs bilateral tactile acuity in a pathway-dependent manner, thus providing unexpected insights into the network mechanisms underlying sensory deficits in PD. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure

    Science.gov (United States)

    Kim, Hak Rim

    2016-01-01

    The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs). EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF) of 835 MHz at a specific absorption rate (SAR) of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress. PMID:27073885

  11. Inputs to the dorsal striatum of the mouse conserve the parallel circuit architecture of the forebrain

    Directory of Open Access Journals (Sweden)

    Weixing X Pan

    2010-12-01

    Full Text Available The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and, manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

  12. Inputs to the dorsal striatum of the mouse reflect the parallel circuit architecture of the forebrain.

    Science.gov (United States)

    Pan, Weixing X; Mao, Tianyi; Dudman, Joshua T

    2010-01-01

    The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

  13. Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum

    Science.gov (United States)

    Goitia, Belen; Garcia-Rill, Edgar; Krasnova, Irina N.; Cadet, Jean Lud; Urbano, Francisco J.; Bisagno, Veronica

    2012-01-01

    Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4×5 mg/kg, i.p., 2 h apart) and modafinil co-administration (2×90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections) on glial cells (microglia and astroglia). We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum. PMID:23056363

  14. The role of the dorsal striatum in extinction: A memory systems perspective.

    Science.gov (United States)

    Goodman, Jarid; Packard, Mark G

    2018-04-01

    The present review describes a role for the dorsal striatum in extinction. Evidence from brain lesion and pharmacological studies indicate that the dorsolateral region of the striatum (DLS) mediates extinction in various maze learning and instrumental learning tasks. Within the context of a multiple memory systems view, the role of the DLS in extinction appears to be selective. Specifically, the DLS mediates extinction of habit memory and is not required for extinction of cognitive memory. Thus, extinction mechanisms mediated by the DLS may involve response-produced inhibition (e.g. inhibition of existing stimulus-response associations or formation of new inhibitory stimulus-response associations), as opposed to cognitive mechanisms (e.g. changes in expectation). Evidence also suggests that NMDA-dependent forms of synaptic plasticity may be part of the mechanism through which the DLS mediates extinction of habit memory. In addition, in some learning situations, DLS inactivation enhances extinction, suggesting a competitive interaction between multiple memory systems during extinction training. Consistent with a multiple memory systems perspective, it is suggested that the DLS represents one of several distinct neural systems that specialize in extinction of different kinds of memory. The relevance of these findings to the development of behavioral and pharmacological therapies that target the maladaptive habit-like symptoms in human psychopathology is also briefly considered. Published by Elsevier Inc.

  15. Volumetry of striatum and pallidum in man--anatomy, cytoarchitecture, connections, MRI and aging.

    Science.gov (United States)

    Brabec, J; Krásený, J; Petrovický, P

    2003-01-01

    For comparing of the pathological and normal healthy state it is essential to obtain sufficient amount of the volumetric data. Nevertheless most of the publicized works use only few healthy controls opposite to the patients for the measuring of the basal ganglia volume. Further essential condition is to take into account the effect of age to the basal ganglia volume in such analysis. The goal of our study was (1) to give the current review of the structure, neurotransmitters, connections and general integration of the basal ganglia in the pathways of the central nervous system, (2) aggregate sufficient amount of volumetric data by virtue of MRI and post-mortem studies, and appoint volumes of the striatum and pallidum, (3) evaluate aging of these structures in adult healthy patients. Another goal was (4) to inspect the correlations between the size of the basal ganglia and volume characteristics of the brain, cranial capacity or frequently measured dimensions within CNS. In the spite of the fact that it is not possible to measure all of these dimensions for clinicians who want to determine if the structure is "normal" or not. Another goal was (5) to find a simple measure, which could serve as the indicator of the real size of structure of the interest. By virtue of the classical anatomical methods and MRI examination we appointed volumes of the striatum (furthermore divided into the complex of the caudatum--nucleus accumbens--CD-Acc and putamen) and pallidum in the sample of 108 healthy adults (18-89 years old). From another measurements we calculated the cranial capacity and volume characteristics of each brain. In a general view that does not respect changes due to age neither volumetric difference between two sexes nor interhemispheric difference was significant for absolute volumes of the striatum, CD-Acc complex, putamen and pallidum. In the case of the striatum, significant correlation between size and age was found (p complex CD-Acc (p = 0.061). Age related

  16. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

    Science.gov (United States)

    Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén

    2017-05-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

  17. In vivo [11C]dihydrotetrabenazine binding in rat striatum: sensitivity to dopamine concentrations

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.; Butch, Elizabeth R.; Desmond, Timothy; Sherman, Phillip; Harris, Paul E.; Frey, Kirk A.

    2010-01-01

    Introduction: The sensitivity of the in vivo binding of [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ) and [ 11 C]methylphenidate ([ 11 C]MPH) to their respective targets - vesicular monoamine transporter type 2 (VMAT2) and neuronal membrane dopamine transporter - after alterations in endogenous levels of dopamine was examined in the rat brain. Methods: In vivo binding of [ 11 C]DTBZ and [ 11 C]MPH was determined using a bolus+infusion protocol. The in vitro number of VMAT2 binding sites was determined by autoradiography. Results: Repeated dosing with α-methyl-p-tyrosine (AMPT) at doses that significantly (-75%) depleted brain tissue dopamine levels resulted in increased (+36%) in vivo [ 11 C]DTBZ binding to VMAT2 in the striatum. The increase in binding could be completely reversed via treatment with L-DOPA/benserazide to restore dopamine levels. There were no changes in the total number of VMAT2 binding sites, as measured using in vitro autoradiography. No changes were observed for in vivo [ 11 C]MPH binding to the dopamine transporter in the striatum following AMPT pretreatment. Conclusion: These results indicate that large reductions in dopamine concentrations in the rat brain can produce modest but significant changes in the binding of radioligands to VMAT2, which can be reversed by replenishment of dopamine using exogenous L-DOPA.

  18. Motor Planning under Unpredictable Reward: Modulations of Movement Vigor and Primate Striatum Activity

    Directory of Open Access Journals (Sweden)

    Ioan eOpris

    2011-05-01

    Full Text Available Although reward probability is an important factor that shapes animal behavior, it is not well understood however, how the primate brain translates reward expectation into the vigor of movement (reaction time and speed. To address this question, we trained two monkeys in a reaction time task that required wrist movements in response to vibrotactile and visual stimuli, with a variable reward schedule. Correct performance was rewarded in 75 % of the trials. Monkeys were certain that they would be rewarded only in the trials immediately following withheld rewards. In these trials, the animals responded sooner and moved faster. Single-unit recordings from the dorsal striatum revealed that modulations in striatal neurons reflected such modulations of movement vigor. First, in the trials with certain rewards, striatal neurons modulated their firing rates earlier. Second, magnitudes of changes in neuronal firing rates depended on whether or not monkeys were certain about the reward. Third, these modulations depended on the sensory modality of the cue (visual vs. vibratory and/or movement direction (flexions vs. extensions. We conclude that dorsal striatum may be a part of the mechanism responsible for the modulation of movement vigor in response to changes of reward predictability.

  19. Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

    Directory of Open Access Journals (Sweden)

    Mariana Raineri

    Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

  20. Individual differences in striatum activity to food commercials predict weight gain in adolescents.

    Science.gov (United States)

    Yokum, Sonja; Gearhardt, Ashley N; Harris, Jennifer L; Brownell, Kelly D; Stice, Eric

    2014-12-01

    Adolescents view thousands of food commercials annually, but little is known about how individual differences in neural response to food commercials relate to weight gain. To add to our understanding of individual risk factors for unhealthy weight gain and environmental contributions to the obesity epidemic, we tested the associations between reward region (striatum and orbitofrontal cortex [OFC]) responsivity to food commercials and future change in body mass index (BMI). Adolescents (N = 30) underwent a scan session at baseline while watching a television show edited to include 20 food commercials and 20 nonfood commercials. BMI was measured at baseline and 1-year follow-up. Activation in the striatum, but not OFC, in response to food commercials relative to nonfood commercials and in response to food commercials relative to the television show was positively associated with change in BMI over 1-year follow-up. Baseline BMI did not moderate these effects. The results suggest that there are individual differences in neural susceptibility to food advertising. These findings highlight a potential mechanism for the impact of food marketing on adolescent obesity. © 2014 The Obesity Society.

  1. Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments

    International Nuclear Information System (INIS)

    Graybiel, A.M.; Moratalla, R.

    1989-01-01

    A major mechanism of neurotransmitter inactivation at catecholaminergic synapses in reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. The authors have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. The authors report here that desipramine-sensitive [ 3 H]mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, [ 3 H]mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, and that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP + ), that depend on the dopamine-uptake complex for entry into neurons

  2. Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments.

    Science.gov (United States)

    Graybiel, A M; Moratalla, R

    1989-01-01

    A major mechanism of neurotransmitter inactivation at catecholaminergic synapses is reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. We have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. We report here that desipramine-sensitive [3H]mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, [3H]mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP+), that depend on the dopamine-uptake complex for entry into neurons. Images PMID:2813436

  3. Comparison of characteristics of dopamine uptake and mazindol binding in mouse striatum.

    Science.gov (United States)

    Zimányi, I; Lajtha, A; Reith, M E

    1989-12-01

    Biochemical and pharmacological studies suggest that the binding of [3H]mazindol is functionally related to the dopamine uptake carrier complex in rodent striatum. In order to study further the relationship between the substrate recognition site for dopamine uptake and the high-affinity binding site for mazindol the uptake of [3H]dopamine and the binding of [3H]mazindol was studied in BALB/cBy mouse striatum in various buffers (Tris, HEPES, bicarbonate-phosphate). Kinetic analysis showed that the Kd of the binding of [3H]mazindol and the Km of the uptake of [3H]dopamine was changed by different sodium concentrations and/or by the presence of Tris, while the Bmax and the Vmax remained essentially the same. However, the shape of the Na+ dependency curves was not the same for mazindol binding and dopamine uptake in the various buffers. The inhibitory effect of other cations such as K+ and Tris was also different on binding and uptake under similar experimental circumstances. Dopamine did not slow down the dissociation of mazindol from its site and this effect was not sodium-sensitive. These complexities can be accommodated by a model that involves overlapping sites for mazindol and dopamine on the dopamine uptake carrier complex, and translocation-reorientation steps.

  4. Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments

    Energy Technology Data Exchange (ETDEWEB)

    Graybiel, A.M.; Moratalla, R. (Massachusetts Institute of Technology, Cambridge (USA))

    1989-11-01

    A major mechanism of neurotransmitter inactivation at catecholaminergic synapses in reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. The authors have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. The authors report here that desipramine-sensitive ({sup 3}H)mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, ({sup 3}H)mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, and that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP{sup +}), that depend on the dopamine-uptake complex for entry into neurons.

  5. Neuronal Adaptation to Amphetamine and Dopamine: Molecular Mechanisms of Prodynorphin Gene Regulation in Rat Striatum

    Science.gov (United States)

    Cole, Rebecca L.; Konradi, Christine; Douglass, James; Hyman, Steven E.

    2014-01-01

    Summary Induction of prodynorphin gene expression by psychostimulant drugs may represent a compensatory adaptation to excessive dopamine stimulation and may contribute to the aversive aspects of withdrawal. We therefore investigated the molecular mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene expression in vivo and in rat primary striatal cultures. We demonstrate that three recently described cAMP response elements (CREs), rather than a previously reported noncanonical AP-1 site, are critical for dopamine induction of the prodynorphin gene in striatal neurons. CRE-binding protein (CREB) binds to these CREs in striatal cell extracts and is phosphorylated on Ser-133 after dopamine stimulation in a D1 dopamine receptor-dependent manner. Surprisingly, following chronic administration of amphetamine, levels of phosphorylated CREB are increased above basal in rat striatum in vivo, whereas c-fos mRNA is suppressed below basal levels. D1 receptor-mediated CREB phosphorylation appears to mediate adaptations to psychostimulant drugs in the striatum. PMID:7718243

  6. Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

    International Nuclear Information System (INIS)

    Fang, Chun-Kai; Chen, Hong-Wen; Wang, Wei-Hsun; Liu, Ren-Shen; Hwang, Jeng-Jong

    2013-01-01

    In this work, we used quantitative autoradiography to study the acute effect of cocaine, methamphetamine, and ketamine on the uptake of [ 18 F]FDOPA in the striatum of rats. Drugs were treated 0.5 h before (pre-treated), and 1.5 h after (post-treated) [ 18 F]FDOPA injections, rats were then sacrificed at 2 h post [ 18 F]FDOPA injections to determine the striatum/frontal cortex binding ratios in the striatum. The ratios were lower in the post-treated groups than those of the pre-treated groups, suggesting a net effect of inhibition of trapping of the tracer. The order of uptake inhibition is: ketamine>methamphetamine>cocaine

  7. Antioxidant responses and photosynthetic behaviors of Kappaphycus alvarezii and Kappaphycus striatum (Rhodophyta, Solieriaceae) during low temperature stress.

    Science.gov (United States)

    Li, Hu; Liu, Jianguo; Zhang, Litao; Pang, Tong

    2016-12-01

    Kappaphycus are farmed in tropical countries as raw material for carrageenan, which is widely used in food industry. The sea area available for farming is one limiting factor in the production of seaweeds. Though cultivation is spreading into subtropical regions, the lower seawater temperature is an important problem encountered in subtropical regions for the farming of Kappaphycus. This research of physiological response to low temperature stress will be helpful for screening Kappaphycus strains for growth in a lower temperature environment. Responses of antioxidant systems and photosystem II (PSII) behaviors in Kappaphycus alvarezii and Kappaphycus striatum were evaluated during low temperature treatments (23, 20, 17 °C). Compared with the controls at 26 °C, the H 2 O 2 concentrations increased in both species when the thalli were exposed to low temperatures (23, 20, 17 °C), but these increases were much greater in K. striatum than in K. alvarezii thalli, suggesting that K. striatum suffered more oxidative stress. The activities of some important antioxidant enzymes (e.g. superoxide dismutase and ascorbate peroxidase) and the hydroxyl free radical scavenging capacity were substantially higher at 23, 20 and 17 °C than at the control 26 °C in K. alvarezii, indicating that the antioxidant system of K. alvarezii enhanced its resistance to low temperature. However, no significant increases of antioxidant enzymes activities were observed at 20 and 17 °C in K. striatum. In addition, both the maximal efficiency of PSII photochemistry (F V /F m ) and the performance index (PI ABS ) decreased significantly in K. striatum at 23 °C, indicating that the photosynthetic apparatus was damaged at 23 °C. In contrast, no significant decreases of either F V /F m or PI ABS were observed in K. alvarezii at 23 °C. It is concluded that K. alvarezii has greater tolerance to low temperature than K. striatum.

  8. Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

    Directory of Open Access Journals (Sweden)

    Julie eBoulanger Bertolus

    2014-05-01

    Full Text Available Interval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days post-natal during odor-fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed.

  9. In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

    2012-10-15

    In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

  10. Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats.

    Science.gov (United States)

    Nyhuis, Tara J; Masini, Cher V; Taufer, Kirsten L; Day, Heidi E W; Campeau, Serge

    2016-01-01

    The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 min of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-h intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-min to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similar attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress.

  11. Comparison of four methods of measurement on [11C]Raclopride  binding potential using regional specificity in the striatum

    DEFF Research Database (Denmark)

    Peterson, Ericka; Gjedde, Albert; Møller, Arne

    Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus  accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing effects of virtually all drugs...... of abuse. Objective/Hypotheses: The sensitivity of the measurement of DA transmission using raclopride as the surrogate marker may be affected by the type of analysis of raclopride binding potential (pB) chosen. Here, we compare striatal pB data obtained using three routine analyses of raclopride data...

  12. Comparison of four methods of measurement on [11C]Raclopride  binding potential using regional specificity in the striatum

    DEFF Research Database (Denmark)

    Peterson, Ericka; Gjedde, Albert; Møller, Arne

    Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus  accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing  effects of virtually all drugs...... of abuse. Objective/Hypotheses: The sensitivity of the measurement of DA transmission using raclopride  as the surrogate marker may be affected by the type of analysis of raclopride binding potential (pB) chosen. Here, we compare  striatal pB data obtained using three routine analyses of raclopride data...

  13. Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving.

    Science.gov (United States)

    Li, Xuan; Witonsky, Kailyn R; Lofaro, Olivia M; Surjono, Felicia; Zhang, Jianjun; Bossert, Jennifer M; Shaham, Yavin

    2018-02-28

    Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R-glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L→DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L→DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT→DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L→DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L→DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L→DMS glutamatergic projections in incubation of drug craving and drug seeking. SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of

  14. Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience

    Science.gov (United States)

    2016-01-01

    The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue–response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel “other” task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue–response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate

  15. Functional Specialization within the Striatum along Both the Dorsal/Ventral and Anterior/Posterior Axes during Associative Learning via Reward and Punishment

    Science.gov (United States)

    Mattfeld, Aaron T.; Gluck, Mark A.; Stark, Craig E. L.

    2011-01-01

    The goal of the present study was to elucidate the role of the human striatum in learning via reward and punishment during an associative learning task. Previous studies have identified the striatum as a critical component in the neural circuitry of reward-related learning. It remains unclear, however, under what task conditions, and to what…

  16. Progressive obtundation in a young woman with bilateral corpus striatum infarction: a case report

    Directory of Open Access Journals (Sweden)

    Zangana Hero M

    2011-07-01

    Full Text Available Abstract Background Bilateral ischemic infarction involving the corpus striatum is a rare event which usually results from global cerebral hypoxia, intoxications, and drug abuse. Case presentation We report a 28 year old Caucasian woman who presented with progressive obtundation and later development of severe expressive dysphasia and Parkinsonism after sustaining ischemic stroke of both corpora striata. Hemorrhagic transformation developed on day four of admission. Conclusion This is a rare case of bilateral basal ganglia infarction with hemorrhagic transformation in a young patient. Our patient's work up did not reveal any cause behind this stroke; however, advanced investigations (such as genetic testing and conventional angiography were not done. The damage resulted in motor dysphasia and Parkinsonism. Neither dystonia nor other involuntary movements developed, and cognitive function was not assessed because of the language disorder.

  17. GABA and Glutamate Synaptic Coadaptations to Chronic Ethanol in the Striatum.

    Science.gov (United States)

    Carlson, Verginia C Cuzon

    2018-02-20

    Alcohol (ethanol) is a widely used and abused drug with approximately 90% of adults over the age of 18 consuming alcohol at some point in their lifetime. Alcohol exerts its actions through multiple neurotransmitter systems within the brain, most notably the GABAergic and glutamatergic systems. Alcohol's actions on GABAergic and glutamatergic neurotransmission have been suggested to underlie the acute behavioral effects of ethanol. The striatum is the primary input nucleus of the basal ganglia that plays a role in motor and reward systems. The effect of ethanol on GABAergic and glutamatergic neurotransmission within striatal circuitry has been thought to underlie ethanol taking, seeking, withdrawal and relapse. This chapter reviews the effects of ethanol on GABAergic and glutamatergic transmission, highlighting the dynamic changes in striatal circuitry from acute to chronic exposure and withdrawal.

  18. Savoring the past: Positive memories evoke value representations in the striatum

    Science.gov (United States)

    Speer, Megan E.; Bhanji, Jamil P.; Delgado, Mauricio R.

    2014-01-01

    Summary Reminders of happy memories can bring back pleasant feelings tied to the original experience, suggesting an intrinsic value in reminiscing about the positive past. However, the neural circuitry underlying the rewarding aspects of autobiographical memory is poorly understood. Using fMRI, we observed enhanced activity during the recall of positive relative to neutral autobiographical memories in corticostriatal circuits that also responded to monetary rewards. Enhanced activity in the striatum and medial prefrontal cortex was associated with increases in positive emotion during recall and striatal engagement further correlated with individual measures of resiliency. Striatal response to the recall of positive memories was greater in individuals whose mood improved after the task. Notably, participants were willing to sacrifice more tangible monetary rewards in order to reminisce about positive past experiences. Our findings suggest that recalling positive autobiographical memories is intrinsically valuable, which may be adaptive for regulating positive emotion and promoting better well-being. PMID:25451197

  19. Effects of the neonicotinoids thiametoxam and clothianidin on in vivo dopamine release in rat striatum.

    Science.gov (United States)

    de Oliveira, Iris Machado; Nunes, Brenda Viviane Ferreira; Barbosa, Durán Rafael; Pallares, Alfonso Miguel; Faro, Lilian Rosana Ferreira

    2010-02-15

    Thiamethoxam (TMX) and clothianidin (CLO) are neonicotinoids insecticides. The main characteristic of these pesticides is their agonist action on nicotinic acetylcholine receptors (nAChRs). In the present work it was studied and characterized the effects of TMX and CLO, in different concentrations, on dopaminergic system of rat striatum using in vivo brain microdialysis coupled to HPLC-EC. Intrastriatal administration of 1mM or 5mM TMX has not produced significant increases on dopamine (DA) levels, nonetheless the infusion of 10mM TMX increases the DA output to 841+/-132%, when compared to basal levels. Infusion of 1mM CLO has not induced a significant increase in DA levels, even so 2, 3.5 and 5mM CLO have produced an increase of 438+/-8%, 2778+/-598% and 4604+/-516%, respectively, every compared to basal levels. Mecamylamine (MEC), a non-competitive nAChRs antagonist, was used to investigate the role of nAChRs on DA release induced by TMX and CLO. The increases in extracellular DA levels induced by TMX and CLO when associated to MEC are 80% and 68% lower than the effect produced by CLO and TMX isolated. These results confirm that TMX and CLO appear to induce in vivo DA increased release in striatum of rats and it seems to be concentration dependent. Moreover, these results indicate that this effect might be related to nAChRs. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  20. Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum.

    Science.gov (United States)

    Muñiz, Javier A; Gomez, Gimena; González, Betina; Rivero-Echeto, María Celeste; Cadet, Jean Lud; García-Rill, Edgar; Urbano, Francisco J; Bisagno, Veronica

    2016-05-01

    Caffeine is the world's most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 × 5 mg/kg), cocaine (3 × 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants.

  1. Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

    Directory of Open Access Journals (Sweden)

    Piechota Marcin

    2006-06-01

    Full Text Available Abstract Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q Khdrbs1 and ATPase Na+/K+ alpha2 subunit (Atp1a2 with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids.

  2. Changes in the development of striatum are involved in repetitive behavior in autism.

    Science.gov (United States)

    Langen, Marieke; Bos, Dienke; Noordermeer, Siri D S; Nederveen, Hilde; van Engeland, Herman; Durston, Sarah

    2014-09-01

    Repetitive behavior is a core feature of autism and has been linked to differences in striatum. In addition, the brain changes associated with autism appear to vary with age. However, most studies investigating striatal differences in autism are cross-sectional, limiting inferences on development. In this study, we set out to 1) investigate striatal development in autism, using a longitudinal design; and 2) examine the relationship between striatal development and repetitive behavior. We acquired longitudinal structural magnetic resonance imaging scans from 86 individuals (49 children with autism, 37 matched control subjects). Each individual was scanned twice, with a mean scan interval time of 2.4 years. Mean age was 9.9 years at time 1 and 12.3 years at time 2. Striatal structures were traced manually with high reliability. Multivariate analyses of variance were used to investigate differences in brain development between diagnostic groups. To examine the relationship with behavior, correlations between changes in brain volumes and clinical measures were calculated. Our results showed an increase in the growth rate of striatal structures for individuals with autism compared with control subjects. The effect was specific to caudate nucleus, where growth rate was doubled. Second, faster striatal growth was correlated with more severe repetitive behavior (insistence on sameness) at the preschool age. This longitudinal study of brain development in autism confirms the involvement of striatum in repetitive behavior. Furthermore, it underscores the significance of brain development in autism, as the severity of repetitive behavior was related to striatal growth, rather than volume per se. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Effects of Ventral Striatum Lesions on Stimulus-Based versus Action-Based Reinforcement Learning.

    Science.gov (United States)

    Rothenhoefer, Kathryn M; Costa, Vincent D; Bartolo, Ramón; Vicario-Feliciano, Raquel; Murray, Elisabeth A; Averbeck, Bruno B

    2017-07-19

    Learning the values of actions versus stimuli may depend on separable neural circuits. In the current study, we evaluated the performance of rhesus macaques with ventral striatum (VS) lesions on a two-arm bandit task that had randomly interleaved blocks of stimulus-based and action-based reinforcement learning (RL). Compared with controls, monkeys with VS lesions had deficits in learning to select rewarding images but not rewarding actions. We used a RL model to quantify learning and choice consistency and found that, in stimulus-based RL, the VS lesion monkeys were more influenced by negative feedback and had lower choice consistency than controls. Using a Bayesian model to parse the groups' learning strategies, we also found that VS lesion monkeys defaulted to an action-based choice strategy. Therefore, the VS is involved specifically in learning the value of stimuli, not actions. SIGNIFICANCE STATEMENT Reinforcement learning models of the ventral striatum (VS) often assume that it maintains an estimate of state value. This suggests that it plays a general role in learning whether rewards are assigned based on a chosen action or stimulus. In the present experiment, we examined the effects of VS lesions on monkeys' ability to learn that choosing a particular action or stimulus was more likely to lead to reward. We found that VS lesions caused a specific deficit in the monkeys' ability to discriminate between images with different values, whereas their ability to discriminate between actions with different values remained intact. Our results therefore suggest that the VS plays a specific role in learning to select rewarded stimuli. Copyright © 2017 the authors 0270-6474/17/376902-13$15.00/0.

  4. The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples

    NARCIS (Netherlands)

    Pennartz, C.M.A.; Lee, E.; Verheul, J.; Lipa, P.; Barnes, C.A.; Mc. Naughton, B.L.

    2004-01-01

    Previously it has been shown that the hippocampus and neocortex can spontaneously reactivate ensemble activity patterns during post-behavioral sleep and rest periods. Here we examined whether such reactivation also occurs in a subcortical structure, the ventral striatum, which receives a direct

  5. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

    NARCIS (Netherlands)

    Westerink, B.H.C.; Kawahara, Y; de Boer, P; Geels, C; de Vries, J.B; Wikström, H.V; van Kalkeren, A; van Vliet, B; Kruse, C.H; Long, S.K

    2001-01-01

    Dose-effect curves were established for the effects of the antipsychotic drugs haloperidol, clozapine, olanzapine, risperidone and ziprasidone on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex, and of dopamine in the striatum. Haloperidol was more effective in

  6. Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model

    DEFF Research Database (Denmark)

    Aidt, Frederik Heurlin; Nielsen, Signe Marie Borch; Kanters, Jørgen

    2013-01-01

    Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system...

  7. Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated with memory of moderate and intense training.

    Science.gov (United States)

    Bello-Medina, Paola C; Flores, Gonzalo; Quirarte, Gina L; McGaugh, James L; Prado Alcalá, Roberto A

    2016-10-18

    A growing body of evidence indicates that treatments that typically impair memory consolidation become ineffective when animals are given intense training. This effect has been obtained by treatments interfering with the neural activity of several brain structures, including the dorsal striatum. The mechanisms that mediate this phenomenon are unknown. One possibility is that intense training promotes the transfer of information derived from the enhanced training to a wider neuronal network. We now report that inhibitory avoidance (IA) induces mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum in rats, which is dependent upon the intensity of the foot-shock used for training; that is, the effect is seen only when high-intensity foot-shock is used in training. We also found that the relative density of thin spines was reduced. These changes were evident at 6 h after training and persisted for at least 24 h afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine density in MSNs in the accumbens was also increased, but the increase did not correlate with the associative process involved in IA; rather, it resulted from the administration of the aversive stimulation alone. These findings suggest that mushroom spines of MSNs of the dorsal striatum receive afferent information that is involved in the integrative activity necessary for memory consolidation, and that intense training facilitates transfer of information from the dorsal striatum to other brain regions through augmented spinogenesis.

  8. Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntington's disease mice.

    Science.gov (United States)

    Achour, Mayada; Le Gras, Stéphanie; Keime, Céline; Parmentier, Frédéric; Lejeune, François-Xavier; Boutillier, Anne-Laurence; Néri, Christian; Davidson, Irwin; Merienne, Karine

    2015-06-15

    Huntington's disease (HD) is a neurodegenerative disease associated with extensive down-regulation of genes controlling neuronal function, particularly in the striatum. Whether altered epigenetic regulation underlies transcriptional defects in HD is unclear. Integrating RNA-sequencing (RNA-seq) and chromatin-immunoprecipitation followed by massively parallel sequencing (ChIP-seq), we show that down-regulated genes in HD mouse striatum associate with selective decrease in H3K27ac, a mark of active enhancers, and RNA Polymerase II (RNAPII). In addition, we reveal that decreased genes in HD mouse striatum display a specific epigenetic signature, characterized by high levels and broad patterns of H3K27ac and RNAPII. Our results indicate that this signature is that of super-enhancers, a category of broad enhancers regulating genes defining tissue identity and function. Specifically, we reveal that striatal super-enhancers display extensive H3K27 acetylation within gene bodies, drive transcription characterized by low levels of paused RNAPII, regulate neuronal function genes and are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Together, our results provide evidence for preferential down-regulation of genes controlled by super-enhancers in HD striatum and indicate that enhancer topography is a major parameter determining the propensity of a gene to be deregulated in a neurodegenerative disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

    Science.gov (United States)

    Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

    2008-04-01

    Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (Self-ratings of alcohol craving. The combination treatment decreased craving for alcohol. Naltrexone with (P = .02) or without (P = .049) ondansetron decreased alcohol cue-induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

  10. Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders.

    Science.gov (United States)

    Rapanelli, M; Frick, L; Pogorelov, V; Ohtsu, H; Bito, H; Pittenger, C

    2017-01-24

    Tic disorders affect ~5% of the population and are frequently comorbid with obsessive-compulsive disorder, autism, and attention deficit disorder. Histamine dysregulation has been identified as a rare genetic cause of tic disorders; mice with a knockout of the histidine decarboxylase (Hdc) gene represent a promising pathophysiologically grounded model. How alterations in the histamine system lead to tics and other neuropsychiatric pathology, however, remains unclear. We found elevated expression of the histamine H3 receptor in the striatum of Hdc knockout mice. The H3 receptor has significant basal activity even in the absence of ligand and thus may modulate striatal function in this knockout model. We probed H3R function using specific agonists. The H3 agonists R-aminomethylhistamine (RAMH) and immepip produced behavioral stereotypies in KO mice, but not in controls. H3 agonist treatment elevated intra-striatal dopamine in KO mice, but not in controls. This was associated with elevations in phosphorylation of rpS6, a sensitive marker of neural activity, in the dorsal striatum. We used a novel chemogenetic strategy to demonstrate that this dorsal striatal activity is necessary and sufficient for the development of stereotypy: when RAMH-activated cells in the dorsal striatum were chemogenetically activated (in the absence of RAMH), stereotypy was recapitulated in KO animals, and when they were silenced the ability of RAMH to produce stereotypy was blocked. These results identify the H3 receptor in the dorsal striatum as a contributor to repetitive behavioral pathology.

  11. Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration.

    Science.gov (United States)

    Gao, Ping; Limpens, Jules H W; Spijker, Sabine; Vanderschuren, Louk J M J; Voorn, Pieter

    2017-03-01

    The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs) implicated in transcriptional regulation, synaptic plasticity and intracellular signalling. However, little is known about how IEG expression patterns change during long-term drug self-administration. The present study, therefore, compares the effects of 10 and 60-day self-administration of cocaine and sucrose on the expression of 17 IEGs in brain regions implicated in addictive behaviour, i.e. dorsal striatum, ventral striatum and medial prefrontal cortex (mPFC). Increased expression after cocaine self-administration was found for 6 IEGs in dorsal and ventral striatum (c-fos, Mkp1, Fosb/ΔFosb, Egr2, Egr4, and Arc) and 10 IEGs in mPFC (same 6 IEGs as in striatum, plus Bdnf, Homer1, Sgk1 and Rgs2). Five of these 10 IEGs (Egr2, Fosb/ΔFosb, Bdnf, Homer1 and Jun) and Trkb in mPFC were responsive to long-term sucrose self-administration. Importantly, no major differences were found between IEG expression patterns after 10 or 60 days of cocaine self-administration, except Fosb/ΔFosb in dorsal striatum and Egr2 in mPFC, whereas the amount of cocaine obtained per session was comparable for short-term and long-term self-administration. These steady changes in IEG expression are, therefore, associated with stable self-administration behaviour rather than the total amount of cocaine consumed. Thus, sustained impulses to IEG regulation during prolonged cocaine self-administration may evoke neuroplastic changes underlying compulsive drug use. © 2015 Society for the Study of Addiction.

  12. Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

    Directory of Open Access Journals (Sweden)

    Hiroaki Kawamichi

    2016-11-01

    Full Text Available Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68. Furthermore, we also conducted a voxel-based morphometry (VBM study of the effects of being in a romantic relationship (N = 113. Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward.

  13. Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness

    Science.gov (United States)

    Kawamichi, Hiroaki; Sugawara, Sho K.; Hamano, Yuki H.; Makita, Kai; Matsunaga, Masahiro; Tanabe, Hiroki C.; Ogino, Yuichi; Saito, Shigeru; Sadato, Norihiro

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68). Furthermore, we also conducted a voxel-based morphometry study of the effects of being in a romantic relationship (N = 113). Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward. PMID:27895606

  14. A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

    Science.gov (United States)

    Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

    2016-12-01

    The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

  15. Brain activation to favorite music in healthy controls and depressed patients.

    Science.gov (United States)

    Osuch, Elizabeth A; Bluhm, Robyn L; Williamson, Peter C; Théberge, Jean; Densmore, Maria; Neufeld, Richard W J

    2009-08-26

    Reward-processing neurocircuitry has been delineated using verbal or visual processing and/or decision-making tasks. We examined more basic processes of listening to enjoyable music in healthy and depressed patients. The paradigm was passive, individualized, and brief. Sixteen depressed and 15 control individuals provided favorite music and identified neutral music from selections provided. In the fMRI scanner, individuals heard their neutral and their favorite music for 3 min each. Favorite versus neutral music-listening contrasts showed greater activation in controls than depressed patients in medial orbital frontal cortex and nucleus accumbens/ventral striatum. Left medial prefrontal cortex activity was positively correlated with pleasure scores, whereas middle temporal cortex and globus pallidus were negatively correlated with pleasure. This paradigm activated neurocircuitry of reward processing and showed clinically meaningful alterations in depression.

  16. Zolpidem in Progressive Supranuclear Palsy

    Directory of Open Access Journals (Sweden)

    Sandip K. Dash

    2013-01-01

    Full Text Available Progressive supranuclear palsy (PSP is a progressive neurodegenerative disorder, characterized by motor symptoms, postural instability, personality changes, and cognitive impairment. There is no effective treatment for this disorder. Reduced neurotransmission of GABA in the striatum and globus pallidus may contribute to the symptoms of motor and cognitive symptoms seen in PSP. Zolpidem is a GABA agonist of the benzodiazepine subreceptor BZ1. Here a nondiabetic, normotensive case of PSP is (Progressive Supranuclear Palsy described, which showed improvement in swallowing, speech, and gaze paresis after zolpidem therapy and possible mechanism of actions are discussed. However, more trials are needed with large number of patients to confirm the effectiveness of zolpidem in progressive supranuclear palsy.

  17. Effects of cyclamen mite (Phytonemus pallidus) and leaf beetle (Galerucella tenella) damage on volatile emission from strawberry (Fragaria x ananassa Duch.) plants and orientation of predatory mites (Neoseiulus cucumeris, N. californicus, and Euseius finlandicus).

    Science.gov (United States)

    Himanen, Sari; Vuorinen, Terhi; Tuovinen, Tuomo; Holopainen, Jarmo K

    2005-11-02

    Volatile emission profile of strawberry (Fragaria x ananassa Duch.) plants (cvs. Polka and Honeoye) damaged by cyclamen mite (Phytonemus pallidus Banks) or leaf beetle Galerucella tenella (L.) (cv. Polka) was analyzed to determine the potential of these strawberry plants to emit herbivore-induced volatiles. The total volatile emissions as well as emissions of many green leaf volatiles (e.g., (Z)-3-hexen-1-ol and (Z)-3-hexenyl acetate) and methyl salicylate were greater from cyclamen mite-damaged strawberry plants than from intact plants. Leaf beetle feeding increased emissions of monoterpenes (Z)-ocimene and (E)-beta-ocimene, sesquiterpenes (E)-beta-caryophyllene, (E,E)-alpha-farnesene, and germacrene-D, and a homoterpene (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) significantly. Nevertheless, the naïve generalist predatory mites, Neoseiulus cucumeris, Neoseiulus californicus, and Euseius finlandicus did not prefer P. pallidus- or G. tenella-damaged plants over intact plants in a Y-tube olfactometer, suggesting that these predatory mite species are not attracted by the herbivore-induced volatiles being released from young strawberry plants.

  18. Radiologic evaluation of globus symptom

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Tae Sub; Lee, Jong Tae; Yoo, Hyung Sik; Suh, Jung Ho; Kim, Ki Whang; Jang, Tae Young; Park, In Yong [Yeonsei University College of Medicine, Seoul (Korea, Republic of)

    1986-12-15

    The globs symptom is a condition in which a patient, often middle aged women, complains of lump and chocking sensation in the throat. Functional disturbance of the cricopharyngeal muscle, rendering it incapable of relaxing during swallowing, has long been recognized as a cause of globs symptom and dysphagia. We wanted to find out how often and to what extent disturbed relaxation of the cricopharyngeal muscle can be seen in patients with globs symptom with routine examination and videoesophagogram. The results were as follow: 1. Male: female ratio was 1:2.4. 2. Globs symptom was most frequent in the age group between 30-39 of female. 3. Organic lesions were seen in 43.6% (24 Pts) of globs patients. 4. Cricopharyngeal muscle was visualized in 29.1% (16 Pts) of globs patients. And other findings were esophageal web in 7.3% (4 Pts), esophageal diverticulum in 3.6% (2 Pts) and degenerative spondylosis in 3.6% (2 Pts). 5. Incidence of visualization of cricopharyngeal muscle were higher in male group (50%) than female one (20.5%). 6. Cricopharyngeal muscle was most frequently visualized on early swallowing phase (12/16 Pts)

  19. Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli.

    Science.gov (United States)

    Siessmeier, Thomas; Kienast, Thorsten; Wrase, Jana; Larsen, Jennifer Lynne; Braus, Dieter F; Smolka, Michael N; Buchholz, Hans Georg; Schreckenberger, Mathias; Rösch, Frank; Cumming, Paul; Mann, Karl; Bartenstein, Peter; Heinz, Andreas

    2006-07-01

    Dopaminergic neurotransmission in the ventral and dorsal striatum interact with central processing of rewarding and reward-indicating stimuli, and may affect frontocortical-striatal-thalamic circuits regulating goal-directed behaviour. Thirteen healthy male volunteers were investigated with multimodal imaging, using the radioligand 6-[(18)F]fluoro-l-DOPA (FDOPA) for positron emission tomography (PET) measurements of dopamine synthesis capacity, and also functional magnetic resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the correlation between FDOPA net blood-brain influx (; ml/g/min) in the ventral and associative dorsal striatum and BOLD signal changes elicited by standardized affectively positive, negative and neutral visual stimuli. The magnitude of in the ventral striatum was positively correlated with BOLD signal increases in the left anterior cingulate cortex and right insular operculum elicited by positive vs. neutral stimuli, but not negative vs. neutral stimuli. In the dorsal striatum, the magnitude of was positively correlated with processing of positive and negative stimuli in the left dorsolateral prefrontal cortex. These findings suggest that dopamine synthesis capacity in the ventral striatum correlates with the attentional processing of rewarding positive stimuli in the anterior cingulate cortex of healthy subjects. Dopaminergic neurotransmission in the associative dorsal striatum has been associated previously with habit learning. The observed correlation between dopamine synthesis capacity in the dorsal striatum and BOLD signal changes in the dorsolateral prefrontal cortex suggests dopaminergic modulation of processing of emotional stimuli in brain areas associated with motor planning and executive behaviour control.

  20. Thalamic involvement in a patient with kernicterus

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, Yueksel [Department of Pediatrics, Marmara University School of Medicine, Istanbul (Turkey); Ekinci, Gazanfer [Department of Radiology, Marmara University School of Medicine, Istanbul (Turkey)

    2002-07-01

    We report the MR imaging findings of a 16-month-old boy with dyskinetic cerebral palsy resulting from kernicterus. T2-weighted images showed symmetric bilateral hyperintensity in the thalamus in addition to the globus pallidus. (orig.)

  1. Structural Findings in the Brain MRI of Patients with Acute Carbon Monoxide Poisoning

    Directory of Open Access Journals (Sweden)

    Yasmin Davoudi

    2014-09-01

    Conclusion: The white matter and globus pallidus were the most common affected regions in brain following acute CO poisoning. Signal abnormalities and restricted diffusion in MRI were correlated with duration of exposure to CO but not with the carboxyhemoglobin levels.

  2. Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus.

    Science.gov (United States)

    Kathirvelu, Balachandar; Colombo, Paul J

    2013-11-01

    Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  3. Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.

    Science.gov (United States)

    Diederen, Kelly M J; Ziauddeen, Hisham; Vestergaard, Martin D; Spencer, Tom; Schultz, Wolfram; Fletcher, Paul C

    2017-02-15

    Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness. SIGNIFICANCE STATEMENT To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that

  4. The Neurotrophic Factor Receptor p75 in the Rat Dorsolateral Striatum Drives Excessive Alcohol Drinking

    Science.gov (United States)

    Darcq, Emmanuel; Morisot, Nadege; Phamluong, Khanhky; Warnault, Vincent; Jeanblanc, Jerome; Longo, Frank M.; Massa, Stephen M.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) signaling in the dorsolateral striatum (DLS) keeps alcohol intake in moderation. For example, activation of the BDNF receptor tropomyosin receptor kinase B (TrkB) in the DLS reduces intake in rats that consume moderate amounts of alcohol. Here, we tested whether long-term excessive consumption of alcohol produces neuroadaptations in BDNF signaling in the rat DLS. We found that BDNF was no longer able to gate alcohol self-administration after a history of repeated cycles of binge alcohol drinking and withdrawal. We then elucidated the possible neuroadaptations that could block the ability of BDNF to keep consumption of alcohol in moderation. We report that intermittent access to 20% alcohol in a two-bottle choice paradigm that models excessive alcohol drinking produces a mobilization of DLS p75 neurotrophin receptor (p75NTR), whose activities oppose those of the Trk receptors, including TrkB. These neuroadaptations were not observed in the DLS of rats exposed to continuous access to 10% alcohol or in rats consuming sucrose. Furthermore, short hairpin RNA (shRNA)-mediated knockdown of the p75NTR gene in the DLS, as well as intra-DLS infusion or systemic administration of the p75NTR modulator, LM11A-31, significantly reduced binge drinking of alcohol. Together, our results suggest that excessive alcohol consumption produces a change in BDNF signaling in the DLS, which is mediated by the recruitment of p75NTR. Our data also imply that modulators of p75NTR signaling could be developed as medications for alcohol abuse disorders. SIGNIFICANCE STATEMENT Neuroadaptations gate or drive excessive, compulsive alcohol drinking. We previously showed that brain-derived neurotrophic factor and its receptor, TrkB, in the dorsolateral striatum (DLS), are part of an endogenous system that keeps alcohol drinking in moderation. Here, we show that a history of excessive alcohol intake produces neuroadaptations in the DLS that preclude BDNF

  5. Regionally distinct phasic dopamine release patterns in the striatum during reversal learning.

    Science.gov (United States)

    Klanker, Marianne; Fellinger, Lisanne; Feenstra, Matthijs; Willuhn, Ingo; Denys, Damiaan

    2017-03-14

    Striatal dopamine (DA) plays a central role in reward-related learning and behavioral adaptation to changing environments. Recent studies suggest that rather than being broadcast as a uniform signal throughout the entire region, DA release dynamics diverge between different striatal regions. In a previous study, we showed that phasic DA release patterns in the ventromedial striatum (VMS) rapidly adapt during reversal learning. However, it is unknown how DA dynamics in the dorsolateral striatum (DLS) are modulated during such adaptive behavior. Here, we used fast-scan cyclic voltammetry to measure phasic DA release in the DLS during spatial reversal learning. In the DLS, we observed minor DA release after the onset of a visual cue signaling reward availability, followed by more pronounced DA release during more proximal reward cues (e.g., lever extension) and execution of the operant response (i.e., lever press), both in rewarded and non-rewarded trials. These release dynamics (minor DA after onset of the predictive visual cue, prominent DA during the operant response) did not change significantly during or following a reversal of response-reward contingencies. Notably, the DA increase to the lever press did not reflect a general signal related to the initiation of any motivated motor response, as we did not observe DA release when rats initiated nose pokes into the food receptacle during inter-trial intervals. This suggests that DA release in the DLS occurs selectively during the initiation and execution of a learned operant response. Together with our previous results obtained in the VMS, these findings reveal distinct phasic DA release patterns during adaptation of established behavior in DLS and VMS. The VMS DA signal, which is highly sensitive to reversal of response-reward contingences, may provide a teaching signal to guide reward-related learning and facilitate behavioral adaptation, whereas DLS DA may reflect a 'response execution signal' largely

  6. Altered effective connectivity network of the basal ganglia in low-grade hepatic encephalopathy: a resting-state fMRI study with Granger causality analysis.

    Directory of Open Access Journals (Sweden)

    Rongfeng Qi

    Full Text Available BACKGROUND: The basal ganglia often show abnormal metabolism and intracranial hemodynamics in cirrhotic patients with hepatic encephalopathy (HE. Little is known about how the basal ganglia affect other brain system and is affected by other brain regions in HE. The purpose of this study was to investigate whether the effective connectivity network associated with the basal ganglia is disturbed in HE patients by using resting-state functional magnetic resonance imaging (rs-fMRI. METHODOLOGY/PRINCIPAL FINDINGS: Thirty five low-grade HE patients and thirty five age- and gender- matched healthy controls participated in the rs-fMRI scans. The effective connectivity networks associated with the globus pallidus, the primarily affected region within basal ganglia in HE, were characterized by using the Granger causality analysis and compared between HE patients and healthy controls. Pearson correlation analysis was performed between the abnormal effective connectivity and venous blood ammonia levels and neuropsychological performances of all HE patients. Compared with the healthy controls, patients with low-grade HE demonstrated mutually decreased influence between the globus pallidus and the anterior cingulate cortex (ACC, cuneus, bi-directionally increased influence between the globus pallidus and the precuneus, and either decreased or increased influence from and to the globus pallidus in many other frontal, temporal, parietal gyri, and cerebellum. Pearson correlation analyses revealed that the blood ammonia levels in HE patients negatively correlated with effective connectivity from the globus pallidus to ACC, and positively correlated with that from the globus pallidus to precuneus; and the number connectivity test scores in patients negatively correlated with the effective connectivity from the globus pallidus to ACC, and from superior frontal gyrus to globus pallidus. CONCLUSIONS/SIGNIFICANCE: Low-grade HE patients had disrupted effective

  7. Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia.

    Science.gov (United States)

    Holubiec, Mariana I; Romero, Juan I; Blanco, Eduardo; Tornatore, Tamara Logica; Suarez, Juan; Rodríguez de Fonseca, Fernando; Galeano, Pablo; Capani, Francisco

    2017-07-13

    Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα). We found a decrease in NAPE-PLD and PPARα expression. Since NAPE-PLD and PPARα take part in the production and reception of biochemical actions of AEs, such as oleoylethanolamide, these results may suggest that PA plays a key role in the regulation of this system. These data agree with previous results obtained in the hippocampus and encourage us to develop further studies using AEs as potential neuroprotective compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

    Science.gov (United States)

    Holz, Nathalie E; Boecker-Schlier, Regina; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2017-02-01

    Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Yearning for connection? Loneliness is associated with increased ventral striatum activity to close others.

    Science.gov (United States)

    Inagaki, Tristen K; Muscatell, Keely A; Moieni, Mona; Dutcher, Janine M; Jevtic, Ivana; Irwin, Michael R; Eisenberger, Naomi I

    2016-07-01

    Loneliness is a distressing state indicating that one's basic need for social connection is not being met. In an effort to satisfy the need for social connection, loneliness may increase the processing of social cues and desire to connect with others. Yet the neural substrates that contribute to the drive for increased connection in response to loneliness are not known. The ventral striatum (VS), previously shown to increase in response to craving food and other rewarding stimuli, may contribute to "social craving" when one is lonely. That is, the VS may track one's 'hunger' for reconnection much as it tracks hunger for food. To examine this, participants reported on their feelings of loneliness before undergoing an fMRI scan where they viewed cues of potential social reconnection (images of a close other). Consistent with the hypothesis that loneliness stems from an unmet need for connection, loneliness was associated with reduced feelings of connection with the close other. Furthermore, greater reported loneliness was associated with increased VS activity to viewing a close other (vs stranger). Results extend the current literature by showing that lonely individuals show increased activity in reward-related regions to their closest loved ones, possibly reflecting an increased desire for social connection. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens

    International Nuclear Information System (INIS)

    Goeders, N.E.; Kuhar, M.J.

    1987-01-01

    A variety of clinical and animal data suggest that the repeated administration of cocaine and related psychomotor stimulants may be associated with a behavioral sensitization whereby the same dose of the drug results in increasing behavioral pathology. This investigation was designed to determine the effects of chronic cocaine administration on the binding of [ 3 H]sulpiride, a relatively specific ligand for D2 dopaminergic receptors, in the rat brain using in vitro homogenate binding and light microscopic quantitative autoradiographic methodologies. Chronic daily injections of cocaine (10 mg/kg, i.p.) for 15 days resulted in a significant decrease in the maximum concentration of sulpiride binding sites in the striatum and a significant increase in the maximum number of these binding sites in the nucleus accumbens. No significant differences in binding affinity were observed in either brain region. These data suggest that chronic cocaine administration may result in differential effects on D2 receptors in the nigro-striatal and mesolimbic dopaminergic systems

  11. Downregulation of the endogenous opioid peptides in the dorsal striatum of human alcoholics

    Directory of Open Access Journals (Sweden)

    Daniil eSarkisyan

    2015-05-01

    Full Text Available The endogenous opioid peptides dynorphins and enkephalins may be involved in brain-area specific synaptic adaptations relevant for different stages of an addiction cycle. We compared the levels of prodynorphin (PDYN and proenkephalin (PENK mRNAs (by qRT-PCR, and dynorphins and enkephalins (by radioimmunoassay in the caudate nucleus and putamen between alcoholics and control subjects. We also evaluated whether PDYN promoter variant rs1997794 associated with alcoholism affects PDYN expression. Postmortem specimens obtained from 24 alcoholics and 26 controls were included in final statistical analysis. PDYN mRNA and Met-enkephalin-Arg-Phe, a marker of PENK were downregulated in the caudate of alcoholics, while PDYN mRNA and Leu-enkephalin-Arg, a marker of PDYN were decreased in the putamen of alcoholics carrying high risk rs1997794 C allele. Downregulation of opioid peptides in the dorsal striatum may contribute to development of alcoholism including changes in goal directed behavior and formation of a compulsive habit in alcoholics.

  12. Differential effects of neural inactivation of the dorsolateral striatum on response and latent extinction.

    Science.gov (United States)

    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2017-04-01

    The present study examined the role of the dorsolateral striatum (DLS) in extinction behavior. Male Long-Evans rats were initially trained on the straight alley maze, in which they were reinforced to traverse a straight runway and retrieve food reward at the opposite end of the maze. After initial acquisition, animals were given extinction training using 1 of 2 distinct protocols: response extinction or latent extinction. For response extinction, the animal was released from the same starting position and had the opportunity to perform the originally reinforced approach response to the goal end of the maze, which no longer contained food. For latent extinction, the animal was confined to the original goal location without food, allowing the animal to form a new cognitive expectation (i.e., that the goal location is no longer reinforced). Immediately before response or latent extinction training, animals received bilateral intra-DLS administration of the sodium channel blocker bupivacaine or control injections of physiological saline. Results indicated that neural inactivation of the DLS with bupivacaine impaired response extinction, but did not influence latent extinction. The dissociation observed indicates that the DLS selectively mediates extinction mechanisms involving suppression of the original response, as opposed to cognitive mechanisms involving a change in expectation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Interest in politics modulates neural activity in the amygdala and ventral striatum.

    Science.gov (United States)

    Gozzi, Marta; Zamboni, Giovanna; Krueger, Frank; Grafman, Jordan

    2010-11-01

    Studies on political participation have found that a person's interest in politics contributes to the likelihood that he or she will be involved in the political process. Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters. Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self-report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion- and reward-related brain areas even when simply agreeing with written political opinions. © 2010 Wiley-Liss, Inc.

  14. Huntington disease: a single-gene degenerative disorder of the striatum.

    Science.gov (United States)

    Nopoulos, Peggy C

    2016-03-01

    Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.

  15. [The action of epidermal growth factor on the development of cultured striatum cells].

    Science.gov (United States)

    Castillo-Díaz, L; Castellano-Benítez, O; Soto-Alonso, J; Rosillo-Martí, J C; de la Cuétara-Bernal, K

    1997-10-01

    Epidermic growth factor (EGF) has a neurotrophic mitogenic effect on different cell populations in the nervous system. This is modulated by the stage of development and microenvironment of the cells. In this paper we describe the action of EGF on embryonic striatum cells of a culture system dissociated from neurons and glias. The cell culture is prepared from 16-17 day rat embryos. In the system used, the cell population was cultured for 20-24 hours in a medium containing serum. This medium was later replaced by a mixture of specific nutrients and treated for 6 days with 20 mg/ml of EGF. The substitution of serum during the initial period of development led to an appreciable reduction in the living cells in the treated cultures and in the controls. The surviving cells were mainly cellular precursors, taking into account their morphological characteristics and capacity for proliferation. The effect of EGF was seen in an increase in the number of cells and was shown to be a stimulus to the proliferation of neuronal and astrocyte precursors. The specific activity of choline acetyl-transferases determined in the cultures at 16 days showed differentiation of a cholinergic neurons subpopulation, which responded to treatment with nerve growth factor with an increase in the activity of this enzyme.

  16. Tetrodotoxin effects in the stimulated acetylcholine release by agonist of glutamate in mice striatum tissue

    International Nuclear Information System (INIS)

    Paes, Paulo Cesar de Arruda; Camillo, Maria A.P.; Rogero, Jose Roberto; Troncone, Lanfranco R.P.

    2002-01-01

    The toxins of animal venoms have been used as important tools for biochemical studies of physiological and pathological processes of diverse systems. In this work we used the action of tetrodotoxin on sodium channels to map the localization of glutamate receptors in cholinergic neurons from striatum tissue of rats. All glutamate receptors are exciting, so they promote the release of other neurotransmitters. In this work we focus on acetylcholine. The localization of glutamate receptor, on the soma or on the excitatory terminal, may contribute for a better understanding of its function. For this work we applied the in vitro method of tritiated neurotransmitter release. The agonists of glutamate receptors chosen were glutamic acid 500μM, NMDA 100μM, kainic acid 300μM, quisqualic acid 300μM and AMPA 1mM. In the first part of the assay the basal and stimulated releases were measured and in the second, the same protocol was performed in the presence of tetrodotoxin 1μM. The reductions observed in basal and stimulated release in the presence of tetrodotoxin suggested that the receptors type AMPA and NMDA were located in soma of cholinergic cell preferentially and the other ones presented a more equilibrate distribution among the axons and the soma. (author)

  17. Mindfulness meditation modulates reward prediction errors in the striatum in a passive conditioning task

    Directory of Open Access Journals (Sweden)

    Ulrich eKirk

    2015-02-01

    Full Text Available Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of rewards and cues that predict reward. Evidence indicates that mindfulness-based approaches reduce reward anticipation signal in the striatum to negative and positive incentives suggesting the hypothesis that such training influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error signals. We found diminished positive and negative prediction error-related blood-oxygen level-dependent (BOLD responses in the putamen in meditators compared with controls. In the meditators, this decrease in striatal BOLD responses to reward prediction was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1 were elevated in both meditators and controls. These results provide evidence that experienced mindfulness meditators show attenuated reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

  18. N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia

    DEFF Research Database (Denmark)

    Sager, T.N.; Laursen, H; Fink-Jensen, A

    1999-01-01

    is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined......]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during...... normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA...

  19. Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum

    Directory of Open Access Journals (Sweden)

    Noël F.

    2000-01-01

    Full Text Available Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.

  20. Dopamine release in ventral striatum during Iowa Gambling Task performance is associated with increased excitement levels in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Møller, Arne; Peterson, Ericka

    2011-01-01

    Aims Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls. Design Pathological Gamblers...... and Healthy Controlswere experimentally compared in a non-gambling (baseline) and gambling condition. Measurements We used Positron Emission Tomography (PET) with the tracer raclopride to measure dopamine D 2/3 receptor availability in the ventral striatum during a non-gambling and gambling condition...... of the Iowa GamblingTask (IGT). After each condition participants rated their excitement level. Setting Laboratory experiment. Participants 18 Pathological Gamblers and 16 Healthy Controls. Findings Pathological Gamblers with dopamine release in the ventral striatum had significantly higher excitement levels...

  1. Glucocorticoid administration into the dorsolateral but not dorsomedial striatum accelerates the shift from a spatial toward procedural memory.

    Science.gov (United States)

    Siller-Pérez, Cristina; Serafín, Norma; Prado-Alcalá, Roberto A; Roozendaal, Benno; Quirarte, Gina L

    2017-05-01

    Glucocorticoid stress hormones are known to enhance the consolidation of hippocampus-dependent spatial and contextual memory. Recent findings indicate that glucocorticoids also enhance the consolidation of procedural memory that relies on the dorsal striatum. The dorsal striatum can be functionally subdivided into the dorsolateral striatum (DLS), which is primarily implicated in shaping procedural memories, and the dorsomedial striatum (DMS), which is engaged in spatial memory. Here, we investigated the hypothesis that posttraining glucocorticoid administration into the DLS promotes the formation of a procedural memory that will normally take place only with extensive training. Male Wistar rats were trained to find a reward in a cross maze that can be solved through either place or response learning. Rats received four trials per day for 5days, a probe trial on Day 6, further training on Days 7-13, and an additional probe trial on Day 14. On Days 2-4 of training, they received posttraining infusions of corticosterone (10 or 30ng) or vehicle into either the DLS or DMS. Rats treated with vehicle into either the DLS or DMS displayed place learning on Day 6 and response learning on Day 14, indicating a shift in control of learned behavior toward a habit-like procedural strategy with extended training. Rats administered corticosterone (10ng) into the DLS displayed response learning on both Days 6 and 14, indicating an accelerated shift to response learning. In contrast, corticosterone administered posttraining into the DMS did not significantly alter the shift from place to response learning. These findings indicate that glucocorticoid administration into the DLS enhances memory consolidation of procedural learning and thereby influences the timing of the switch from the use of spatial/contextual memory to habit-like procedural memory to guide behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior.

    Science.gov (United States)

    Pauli, Wolfgang M; Clark, Alexandra D; Guenther, Heidi J; O'Reilly, Randall C; Rudy, Jerry W

    2012-06-20

    Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.

  3. Nicotine-induced and D1-receptor-dependent dendritic remodeling in a subset of dorsolateral striatum medium spiny neurons.

    Science.gov (United States)

    Ehlinger, Daniel G; Burke, Julian C; McDonald, Craig G; Smith, Robert F; Bergstrom, Hadley C

    2017-07-25

    Nicotine is one of the most addictive substances known, targeting multiple memory systems, including the ventral and dorsal striatum. One form of neuroplasticity commonly associated with nicotine is dendrite remodeling. Nicotine-induced dendritic remodeling of ventral striatal medium spiny neurons (MSNs) is well-documented. Whether MSN dendrites in the dorsal striatum undergo a similar pattern of nicotine-induced structural remodeling is unknown. A morphometric analysis of Golgi-stained MSNs in rat revealed a natural asymmetry in dendritic morphology across the mediolateral axis, with larger, more complex MSNs found in the dorsolateral striatum (DLS). Chronic nicotine produced a lasting (at least 21day) expansion in the dendritic complexity of MSNs in the DLS, but not dorsomedial striatum (DMS). Given prior evidence that MSN subtypes can be distinguished based on dendritic morphology, MSNs were segregated into morphological subpopulations based on the number of primary dendrites. Analysis of these subpopulations revealed that DLS MSNs with more primary dendrites were selectively remodeled by chronic nicotine exposure and remodeling was specific to the distal-most portions of the dendritic arbor. Co-administration of the dopamine D1 receptor (D1R) antagonist SCH23390 completely reversed the selective effects of nicotine on DLS MSN dendrite morphology, supporting a causal role for dopamine signaling at D1 receptors in nicotine-induced dendrite restructuring. Considering the functional importance of the DLS in shaping and expressing habitual behavior, these data support a model in which nicotine induces persistent and selective changes in the circuit connectivity of the DLS that may promote and sustain addiction-related behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Differential Arc expression in the hippocampus and striatum during the transition from attentive to automatic navigation on a plus maze

    Science.gov (United States)

    Gardner, Robert S.; Suarez, Daniel F.; Robinson-Burton, Nadira K.; Rudnicky, Christopher J.; Gulati, Asish; Ascoli, Giorgio A.; Dumas, Theodore C.

    2016-01-01

    The strategies utilized to effectively perform a given task change with practice and experience. During a spatial navigation task, with relatively little training, performance is typically attentive enabling an individual to locate the position of a goal by relying on spatial landmarks. These (place) strategies require an intact hippocampus. With task repetition, performance becomes automatic; the same goal is reached using a fixed response or sequence of actions. These (response) strategies require an intact striatum. The current work aims to understand the activation patterns across these neural structures during this experience-dependent strategy transition. This was accomplished by region-specific measurement of activity-dependent immediate early gene expression among rats trained to different degrees on a dual-solution task (i.e., a task that can be solved using either place or response navigation). As expected, rats increased their reliance on response navigation with extended task experience. In addition, dorsal hippocampal expression of the immediate early gene Arc was considerably reduced in rats that used a response strategy late in training (as compared with hippocampal expression in rats that used a place strategy early in training). In line with these data, vicarious trial and error, a behavior linked to hippocampal function, also decreased with task repetition. Although Arc mRNA expression in dorsal medial or lateral striatum alone did not correlate with training stage, the ratio of expression in the medial striatum to that in the lateral striatum was relatively high among rats that used a place strategy early in training as compared with the ratio among over-trained response rats. Altogether, these results identify specific changes in the activation of dissociated neural systems that may underlie the experience-dependent emergence of response-based automatic navigation. PMID:26976088

  5. Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

    Directory of Open Access Journals (Sweden)

    Makoto Ito

    2015-11-01

    Full Text Available Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS, the dorsomedial striatum (DMS, and the ventral striatum (VS identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

  6. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    OpenAIRE

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly...

  7. Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

    Science.gov (United States)

    Ito, Makoto; Doya, Kenji

    2015-11-01

    Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS), the dorsomedial striatum (DMS), and the ventral striatum (VS) identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

  8. Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

    OpenAIRE

    Hiroaki Kawamichi; Hiroaki Kawamichi; Hiroaki Kawamichi; Sho K Sugawara; Yuki H Hamano; Yuki H Hamano; Kai Makita; Masahiro Matsunaga; Hiroki C Tanabe; Yuichi Ogino; Shigeru Saito; Norihiro Sadato; Norihiro Sadato

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

  9. Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness

    OpenAIRE

    Kawamichi, Hiroaki; Sugawara, Sho K.; Hamano, Yuki H.; Makita, Kai; Matsunaga, Masahiro; Tanabe, Hiroki C.; Ogino, Yuichi; Saito, Shigeru; Sadato, Norihiro

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

  10. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  11. Prenatal ethanol exposure alters synaptic plasticity in the dorsolateral striatum of rat offspring via changing the reactivity of dopamine receptor.

    Directory of Open Access Journals (Sweden)

    Rong Zhou

    Full Text Available Prenatal exposure to high-level ethanol (EtOH has been reported to produce hyperlocomotion in offspring. Previous studies have demonstrated synaptic plasticity in cortical afferent to the dorsolateral (DL striatum is involved in the pathogensis of hyperlocomotion. Here, prenatal EtOH-exposed rat offspring were used to investigate whether maternal EtOH exposure affected synaptic plasticity in the DL striatum. We found high-frequency stimulation (HFS induced a weaker long-term potentiation (LTP in EtOH rats than that in control rats at postnatal day (PD 15. The same protocol of HFS induced long-term depression (LTD in control group but still LTP in EtOH group at PD 30 or PD 40. Furthermore, enhancement of basal synaptic transmission accompanied by the decrease of pair-pulse facilitation (PPF was observed in PD 30 EtOH offspring. The perfusion with D1-type receptors (D1R antagonist SCH23390 recovered synaptic transmission and blocked the induction of abnormal LTP in PD 30 EtOH offspring. The perfusion with D2-type receptors (D2R agonist quinpirole reversed EtOH-induced LTP into D1R- and metabotropic glutamate receptor-dependent LTD. The data provide the functional evidence that prenatal ethanol exposure led to the persistent abnormal synaptic plasticity in the DL striatum via disturbing the balance between D1R and D2R.

  12. Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

    Science.gov (United States)

    Pan, Pedro Mario; Sato, João R; Salum, Giovanni A; Rohde, Luis A; Gadelha, Ary; Zugman, Andre; Mari, Jair; Jackowski, Andrea; Picon, Felipe; Miguel, Eurípedes C; Pine, Daniel S; Leibenluft, Ellen; Bressan, Rodrigo A; Stringaris, Argyris

    2017-11-01

    Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.

  13. Segmentation of the Striatum from MR Brain Images to Calculate the -TRODAT-1 Binding Ratio in SPECT Images

    Directory of Open Access Journals (Sweden)

    Ching-Fen Jiang

    2013-01-01

    Full Text Available Quantification of regional -TRODAT-1 binding ratio in the striatum regions in SPECT images is essential for differential diagnosis between Alzheimer's and Parkinson's diseases. Defining the region of the striatum in the SPECT image is the first step toward success in the quantification of the TRODAT-1 binding ratio. However, because SPECT images reveal insufficient information regarding the anatomical structure of the brain, correct delineation of the striatum directly from the SPECT image is almost impossible. We present a method integrating the active contour model and the hybrid registration technique to extract regions from MR T1-weighted images and map them into the corresponding SPECT images. Results from three normal subjects suggest that the segmentation accuracy using the proposed method was compatible with the expert decision but has a higher efficiency and reproducibility than manual delineation. The binding ratio derived by this method correlated well (R2 = 0.76 with those values calculated by commercial software, suggesting the feasibility of the proposed method.

  14. A fundamental study on accumulation of [125I]IBZM in the rat striatum and on effect of non-labeled ligand

    International Nuclear Information System (INIS)

    Ishikawa, Nobuyoshi; Nakamura, Toshihiko; Satou, Motohiro; Takeda, Tohoru; Wu, Jin; Motoji, Naomi; Shigematsu, Akiyo.

    1995-01-01

    Iodo-125-labeled iodobenzamide ([ 125 I]IBZM) is used as a specific binding radioligand to dopamine D 2 receptors with high affinity and selectivity. The radioligand was homogeneously distributed in the whole brain initially after anministration, and rapidly washed out from the dopamine receptor-poor area followed by persistent retention in the striatum. Regression curve generated from striatum/cortex PSL ratio indicated the constant washout rate from striatum and cortex respectively. In the pretreated rat by cold benzamide (2 mg/kg), the accumulation of the radioligand was significantly suppressed in the striatum (48.8%). Iodine-125-labeled iodo-benzamide has the promise for investigation of dopamine D 2 receptors in the living brain. (author)

  15. Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain

    International Nuclear Information System (INIS)

    Maeda, H.; Sato, M.; Yoshikawa, A.; Kimura, M.; Sonomura, T.; Terada, M.; Kishi, K.

    1997-01-01

    In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 ± 0.38, 2.12 ± 0.37, and 1.38 ± 0.24 (μg/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50 % more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus. (orig.). With 2 figs., 2 tabs

  16. Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

    Science.gov (United States)

    Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

    2009-01-01

    Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

  17. Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

    Science.gov (United States)

    Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

    2009-02-11

    Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

  18. Methyllycaconitine prevents methamphetamine-induced effects in mouse striatum: involvement of alpha7 nicotinic receptors.

    Science.gov (United States)

    Escubedo, Elena; Chipana, Carlos; Pérez-Sánchez, Mónica; Camarasa, Jordi; Pubill, David

    2005-11-01

    In a previous study, we demonstrated that in rat striatal synaptosomes, methamphetamine (METH)-induced reactive oxygen species (ROS) production was prevented by methyllycaconitine (MLA), a specific antagonist of alpha7 neuronal nicotinic acetylcholine receptors (alpha7 nAChR). The aim of this study was to test the influence of MLA on acute METH effects and neurotoxicity in mice, using both in vivo and in vitro models. MLA inhibited METH-induced climbing behavior by 50%. Acute effects after 30-min preincubation with 1 microM METH also included a decrease in striatal synaptosome dopamine (DA) uptake, which was prevented by MLA. METH-induced neurotoxicity was assessed in vivo in terms of loss of striatal dopaminergic terminals (73%) and of tyrosine hydroxylase levels (by 90%) at 72 h post-treatment, which was significantly attenuated by MLA. Microglial activation [measured as 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide binding] was also present at 24 h post-treatment and was fully prevented by MLA, tending to confirm its neuroprotective activity. MLA had no effect on METH-induced hyperthermia. Additionally, flow cytometry assays showed that METH-induced ROS generation occurs inside synaptosomes from mouse striatum. This effect implied release of vesicular DA and was calcium-, neuronal nitric-oxide synthase-, and protein kinase C-dependent. MLA and alpha-bungarotoxin, but not dihydro-beta-erythroidine (an antagonist that blocks nAChR-containing beta2 subunits), fully prevented METH-induced ROS production without affecting vesicular DA uptake. The importance of this study lies not only in the neuroprotective effect elicited by the blockade of the alpha7 nicotinic receptors by MLA but also in that it proposes a new mechanism with which to study METH-induced acute and long-term effects.

  19. Enhancing and impairing extinction of habit memory through modulation of NMDA receptors in the dorsolateral striatum.

    Science.gov (United States)

    Goodman, Jarid; Ressler, Reed L; Packard, Mark G

    2017-06-03

    The present experiments investigated the involvement of N-methyl-d-aspartate (NMDA) receptors of the dorsolateral striatum (DLS) in consolidation of extinction in a habit memory task. Adult male Long-Evans rats were initially trained in a food-reinforced response learning version of a plus-maze task and were subsequently given extinction training in which the food was removed from the maze. In experiment 1, immediately after the first day of extinction training, rats received bilateral intra-DLS injections of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 2µg/side) or physiological saline. In experiment 2, immediately following the first day of extinction training, animals were given intra-DLS injections of NMDA receptor partial agonist d-cycloserine (DCS; 10 or 20µg/side) or saline. In both experiments, the number of perseverative trials (a trial in which a rat made the same previously reinforced body-turn response) and latency to reach the previously correct food well were used as measures of extinction behavior. Results indicated that post-training intra-DLS injections of AP5 impaired extinction. In contrast, post-training intra-DLS infusions of DCS (20µg) enhanced extinction. Intra-DLS administration of AP5 or DCS given two hours after extinction training did not influence extinction of response learning, indicating that immediate post-training administration of AP5 and DCS specifically influenced consolidation of the extinction memory. The present results indicate a critical role for DLS NMDA receptors in modulating extinction of habit memory and may be relevant to developing therapeutic approaches to combat the maladaptive habits observed in human psychopathologies in which DLS-dependent memory has been implicated (e.g. drug addiction and relapse and obsessive compulsive disorder). Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Stress-related anhedonia is associated with ventral striatum reactivity to reward and transdiagnostic psychiatric symptomatology

    Science.gov (United States)

    Corral-Frías, Nadia S.; Nikolova, Yuliya S.; Michalski, Lindsay J.; Baranger, David A.A.; Hariri, Ahmad R.; Bogdan, Ryan

    2015-01-01

    Background Early life stress (ELS) is consistently associated with increased risk for subsequent psychopathology. Individual differences in neural response to reward may confer vulnerability to stress-related psychopathology. Using data from the ongoing Duke Neurogenetics Study, the present study examined whether reward-related ventral striatum (VS) reactivity moderates the relationship between retrospectively reported ELS and anhedonic symptomatology. We further assessed whether individual differences in reward-related VS reactivity were associated with other depressive symptoms and problematic alcohol use via stress-related anhedonic symptoms and substance use-associated coping. Method Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) was collected while participants (n = 906) completed a card-guessing task, which robustly elicits VS reactivity. ELS, anhedonic symptoms, other depressive symptoms, coping behavior, and alcohol use behavior were assessed with self-report questionnaires. Linear regressions were run to examine whether VS reactivity moderated the relationship between ELS and anhedonic symptoms. Structural equation models examined whether this moderation was indirectly associated with other depression symptoms and problematic alcohol use through its association with anhedonia. Results Analyses of data from 820 participants passing quality control procedures revealed that the VS × ELS interaction was associated with anhedonic symptoms (p = 0.011). Moreover, structural equation models indirectly linked this interaction to non-anhedonic depression symptoms and problematic alcohol use through anhedonic symptoms and substance-related coping. Conclusions These findings suggest that reduced VS reactivity to reward is associated with increased risk for anhedonia in individuals exposed to ELS. Such stress-related anhedonia is further associated with other depressive symptoms and problematic alcohol use through substance-related coping

  1. Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

    Directory of Open Access Journals (Sweden)

    John M Burkhardt

    2009-10-01

    Full Text Available Previous studies showed that dopamine depletion leads to both changes in firing rate and in neuronal synchrony in the basal ganglia. Since dopamine D1 and D2 receptors are preferentially expressed in striatonigral and striatopallidal medium spiny neurons, respectively, we investigated the relative contribution of lack of D1 and/or D2-type receptor activation to the changes in striatal firing rate and synchrony observed after dopamine depletion. Similar to what was observed after dopamine depletion, co-administration of D1 and D2 antagonists to mice chronically implanted with multielectrode arrays in the striatum caused significant changes in firing rate, power of the local field potential (LFP oscillations, and synchrony measured by the entrainment of neurons to striatal local field potentials. However, although blockade of either D1 or D2 type receptors produced similarly severe akinesia, the effects on neural activity differed. Blockade of D2 receptors affected the firing rate of medium spiny neurons and the power of the LFP oscillations substantially, but it did not affect synchrony to the same extent. In contrast, D1 blockade affected synchrony dramatically, but had less substantial effects on firing rate and LFP power. Furthermore, there was no consistent relation between neurons changing firing rate and changing LFP entrainment after dopamine blockade. Our results suggest that the changes in rate and entrainment to the LFP observed in medium spiny neurons after dopamine depletion are somewhat dissociable, and that lack of D1- or D2-type receptor activation can exert independent yet interactive pathological effects during the progression of Parkinson’s disease.

  2. Craving behavioral intervention for internet gaming disorder: remediation of functional connectivity of the ventral striatum.

    Science.gov (United States)

    Zhang, Jin-Tao; Ma, Shan-Shan; Li, Chiang-Shan R; Liu, Lu; Xia, Cui-Cui; Lan, Jing; Wang, Ling-Jiao; Liu, Ben; Yao, Yuan-Wei; Fang, Xiao-Yi

    2018-01-01

    Psychobehavioral intervention is an effective treatment of Internet addiction, including Internet gaming disorder (IGD). However, the neural mechanisms underlying its efficacy remain unclear. Cortical-ventral striatum (VS) circuitry is a common target of psychobehavioral interventions in drug addiction, and cortical-VS dysfunction has been reported in IGD; hence, the primary aim of the study was to investigate how the VS circuitry responds to psychobehavioral interventions in IGD. In a cross-sectional study, we examined resting-state functional connectivity of the VS in 74 IGD subjects (IGDs) and 41 healthy controls (HCs). In a follow-up craving behavioral intervention (CBI) study, of the 74 IGD subjects, 20 IGD subjects received CBI (CBI+) and 16 IGD subjects did not (CBI-). All participants were scanned twice with similar time interval to assess the effects of CBI. IGD subjects showed greater resting-state functional connectivity of the VS to left inferior parietal lobule (lIPL), right inferior frontal gyrus and left middle frontal gyrus, in positive association with the severity of IGD. Moreover, compared with CBI-, CBI+ showed significantly greater decrease in VS-lIPL connectivity, along with amelioration in addiction severity following the intervention. These findings demonstrated that functional connectivity between VS and lIPL, each presumably mediating gaming craving and attentional bias, may be a potential biomarker of the efficacy of psychobehavioral intervention. These results also suggested that non-invasive techniques such as transcranial magnetic or direct current stimulation targeting the VS-IPL circuitry may be used in the treatment of Internet gaming disorders. © 2016 Society for the Study of Addiction.

  3. Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention

    International Nuclear Information System (INIS)

    Tomasi, D.; Fowler, J.; Tomasi, D.; Volkow, N.D.; Wang, R.L.; Telang, F.; Wang, Chang L.; Ernst, T.; Fowler, J.S.

    2009-01-01

    Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [ 11 C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus. These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.

  4. Dopamine transporters in striatum correlate with deactivation in the default mode network during visuospatial attention.

    Directory of Open Access Journals (Sweden)

    Dardo Tomasi

    2009-06-01

    Full Text Available Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN. Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task.For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [(11C]cocaine used as DAT radiotracer and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7 and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32. With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus.These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness and cingulate gyrus (region deactivated in proportion to emotional interference. These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT in inattention reflect in part their ability to facilitate the deactivation of the DMN.

  5. Spiny Neurons of Amygdala, Striatum and Cortex Use Dendritic Plateau Potentials to Detect Network UP States

    Directory of Open Access Journals (Sweden)

    Katerina D Oikonomou

    2014-09-01

    Full Text Available Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: [1] they are the most abundant cell type within their respective brain area, [2] covered by thousands of thorny protrusions (dendritic spines, [3] possess high levels of dendritic NMDA conductances, and [4] experience sustained somatic depolarizations in vivo and in vitro (UP states. In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (dendritic UP states characterized by (i fast rise, (ii plateau phase lasting several hundred milliseconds and (iii abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates towards the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200 – 800 ms steady depolarization (~20 mV amplitude, which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states. We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

  6. Post-training cocaine administration facilitates habit learning and requires the infralimbic cortex and dorsolateral striatum.

    Science.gov (United States)

    Schmitzer-Torbert, Neil; Apostolidis, Steven; Amoa, Romeo; O'Rear, Connor; Kaster, Michael; Stowers, Josh; Ritz, Robert

    2015-02-01

    Human drug addiction is a complex disorder, in which exogenous substances are able to recruit and maintain behaviors involved in drug taking. Many drugs that are addictive in humans are able to act on natural brain systems for learning and memory, and while many memory systems may be affected by addictive drugs, work with operant tasks has shown that addictive drugs (e.g. cocaine and alcohol) are particularly effective in recruiting habit learning systems, compared to natural rewards. It is currently unknown if the ability of addictive drugs to facilitate habit learning depends on a direct action on habit learning systems in the brain, versus the rewarding properties of drug administration. To differentiate between these options, rats were trained to perform two actions (lever pressing), each of which was rewarded with a different natural reward. After acquiring the behavior, rats received three training sessions which were followed by post-training injections of saline or cocaine (5 or 10mg/kg, i.p.). Using sensory-specific satiety, extinction tests revealed that lever pressing for actions which were paired with saline were sensitive to devaluation (typical of goal-directed behaviors) while actions which were paired with cocaine were not sensitive to devaluation (typical of habitual behaviors). Lesions of the infralimbic or dorsolateral striatum were able to block the action of post-training cocaine injections. These data indicate that, within individual rats, cocaine injections facilitate the transition of behavior to habitual control for actions that have been recently performed, without a general facilitation of habit learning, and that this action of cocaine requires brain areas that are critical for learning natural habits. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Dopamine Transporters in Striatum Correlated with Deactivation in the Default Mode Network during Visuospatial Attention

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi, D.; Fowler, J.; Tomasi, D.; Volkow, N.D.; Wang, R.L.; Telang, F.; Wang, Chang, L.; Ernst, T.; /Fowler, J.S.

    2009-06-01

    Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [{sup 11}C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus. These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.

  8. Glucocorticoid enhancement of dorsolateral striatum-dependent habit memory requires concurrent noradrenergic activity.

    Science.gov (United States)

    Goodman, J; Leong, K-C; Packard, M G

    2015-12-17

    Previous findings indicate that post-training administration of glucocorticoid stress hormones can interact with the noradrenergic system to enhance consolidation of hippocampus- or amygdala-dependent cognitive/emotional memory. The present experiments were designed to extend these findings by examining the potential interaction of glucocorticoid and noradrenergic mechanisms in enhancement of dorsolateral striatum (DLS)-dependent habit memory. In experiment 1, different groups of adult male Long-Evans rats received training in two DLS-dependent memory tasks. In a cued water maze task, rats were released from various start points and were reinforced to approach a visibly cued escape platform. In a response-learning version of the water plus-maze task, animals were released from opposite starting positions and were reinforced to make a consistent egocentric body-turn to reach a hidden escape platform. Immediately post-training, rats received peripheral injections of the glucocorticoid corticosterone (1 or 3 mg/kg) or vehicle solution. In both tasks, corticosterone (3 mg/kg) enhanced DLS-dependent habit memory. In experiment 2, a separate group of animals received training in the response learning version of the water plus-maze task and were given peripheral post-training injections of corticosterone (3 mg/kg), the β-adrenoreceptor antagonist propranolol (3 mg/kg), corticosterone and propranolol concurrently, or control vehicle solution. Corticosterone injections again enhanced DLS-dependent memory, and this effect was blocked by concurrent administration of propranolol. Propranolol administration by itself (3 mg/kg) did not influence DLS-dependent memory. Taken together, the findings indicate an interaction between glucocorticoid and noradrenergic mechanisms in DLS-dependent habit memory. Propranolol administration may be useful in treating stress-related human psychopathologies associated with a dysfunctional DLS-dependent habit memory system. Copyright © 2015

  9. Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder.

    Science.gov (United States)

    Posner, Jonathan; Marsh, Rachel; Maia, Tiago V; Peterson, Bradley S; Gruber, Allison; Simpson, H Blair

    2014-06-01

    Cortico-striato-thalamo-cortical (CSTC) loops project from the cortex to the striatum, then from the striatum to the thalamus via the globus pallidus, and finally from the thalamus back to the cortex again. These loops have been implicated in Obsessive-Compulsive Disorder (OCD) with particular focus on the limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate cortices, as well as the ventral striatum. Resting state functional-connectivity MRI (rs-fcMRI) studies, which examine temporal correlations in neural activity across brain regions at rest, have examined CSTC loop connectivity in patients with OCD and suggest hyperconnectivity within these loops in medicated adults with OCD. We used rs-fcMRI to examine functional connectivity within CSTC loops in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20). Contrary to prior rs-fcMRI studies in OCD patients on medications that report hyperconnectivity in the limbic CSTC loop, we found that compared with HCs, unmedicated OCD participants had reduced connectivity within the limbic CSTC loop. Exploratory analyses revealed that reduced connectivity within the limbic CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential confounding effects of antidepressants on connectivity measures and the value of future examinations of the effects of pharmacological and/or behavioral treatments on limbic CSTC loop connectivity. Copyright © 2013 Wiley Periodicals, Inc.

  10. Involvement of dopamine loss in extrastriatal basal ganglia nuclei in the pathophysiology of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Abdelhamid eBenazzouz

    2014-05-01

    Full Text Available Parkinson’s disease is a neurological disorder characterized by the manifestation of motor symptoms, such as akinesia, muscle rigidity and tremor at rest. These symptoms are classically attributed to the degeneration of dopamine neurons in the pars compacta of substantia nigra (SNc, which results in a marked dopamine depletion in the striatum. It is well established that dopamine neurons in the SNc innervate not only the striatum, which is the main target, but also other basal ganglia nuclei including the two segments of globus pallidus and the subthalamic nucleus. The role of dopamine and its depletion in the striatum is well known, however, the role of dopamine depletion in the pallidal complex and the subthalamic nucleus in the genesis of their abnormal neuronal activity and in parkinsonian motor deficits is still not clearly determined. Based on recent experimental data from animal models of Parkinson's disease in rodents and non-human primates and also from parkinsonian patients, this review summarizes current knowledge on the role of dopamine in the modulation of basal ganglia neuronal activity and also the role of dopamine depletion in these nuclei in the pathophysiology of Parkinson's disease.

  11. Aberrant topology of striatum's connectivity is associated with the number of episodes in depression.

    Science.gov (United States)

    Meng, Chun; Brandl, Felix; Tahmasian, Masoud; Shao, Junming; Manoliu, Andrei; Scherr, Martin; Schwerthöffer, Dirk; Bäuml, Josef; Förstl, Hans; Zimmer, Claus; Wohlschläger, Afra M; Riedl, Valentin; Sorg, Christian

    2014-02-01

    In major depressive disorder, depressive episodes reoccur in ∼60% of cases; however, neural mechanisms of depressive relapse are poorly understood. Depressive episodes are characterized by aberrant topology of the brain's intrinsic functional connectivity network, and the number of episodes is one of the most important predictors for depressive relapse. In this study we hypothesized that specific changes of the topology of intrinsic connectivity interact with the course of episodes in recurrent depressive disorder. To address this hypothesis, we investigated which changes of connectivity topology are associated with the number of episodes in patients, independently of current symptoms and disease duration. Fifty subjects were recruited including 25 depressive patients (two to 10 episodes) and 25 gender- and age-matched control subjects. Resting-state functional magnetic resonance imaging, Harvard-Oxford brain atlas, wavelet-transformation of atlas-shaped regional time-series, and their pairwise Pearson's correlation were used to define individual connectivity matrices. Matrices were analysed by graph-based methods, resulting in outcome measures that were used as surrogates of intrinsic network topology. Topological scores were subsequently compared across groups, and, for patients only, related with the number of depressive episodes and current symptoms by partial correlation analysis. Concerning the whole brain connectivity network of patients, small-world topology was preserved but global efficiency was reduced and global betweenness-centrality increased. Aberrant nodal efficiency and centrality of regional connectivity was found in the dorsal striatum, inferior frontal and orbitofrontal cortex as well as in the occipital and somatosensory cortex. Inferior frontal changes were associated with current symptoms, whereas aberrant right putamen network topology was associated with the number of episodes. Results were controlled for effects of total grey matter

  12. Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1Receptor Heteromers in the Dorsal Striatum.

    Science.gov (United States)

    Moreno, Estefanía; Chiarlone, Anna; Medrano, Mireia; Puigdellívol, Mar; Bibic, Lucka; Howell, Lesley A; Resel, Eva; Puente, Nagore; Casarejos, María J; Perucho, Juan; Botta, Joaquín; Suelves, Nuria; Ciruela, Francisco; Ginés, Silvia; Galve-Roperh, Ismael; Casadó, Vicent; Grandes, Pedro; Lutz, Beat; Monory, Krisztina; Canela, Enric I; Lluís, Carmen; McCormick, Peter J; Guzmán, Manuel

    2018-04-01

    The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A 2A receptor (A 2A R) and cannabinoid CB 1 receptor (CB 1 R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A 2A R and CB 1 R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A 2A R-CB 1 R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically modified animal models, together with biochemical and pharmacological approaches, we provide a high-resolution expression map and a detailed functional characterization of A 2A R-CB 1 R heteromers in the dorsal striatum. Specifically, our data unveil that the A 2A R-CB 1 R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington's disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases.

  13. Primary food reward and reward-predictive stimuli evoke different patterns of phasic dopamine signaling throughout the striatum.

    Science.gov (United States)

    Brown, Holden D; McCutcheon, James E; Cone, Jackson J; Ragozzino, Michael E; Roitman, Mitchell F

    2011-12-01

    Phasic changes in dopamine activity play a critical role in learning and goal-directed behavior. Unpredicted reward and reward-predictive cues evoke phasic increases in the firing rate of the majority of midbrain dopamine neurons--results that predict uniformly broadcast increases in dopamine concentration throughout the striatum. However, measurement of dopamine concentration changes during reward has cast doubt on this prediction. We systematically measured phasic changes in dopamine in four striatal subregions [nucleus accumbens shell and core (Core), dorsomedial (DMS) and dorsolateral striatum] in response to stimuli known to activate a majority of dopamine neurons. We used fast-scan cyclic voltammetry in awake and behaving rats, which measures changes in dopamine on a similar timescale to the electrophysiological recordings that established a relationship between phasic dopamine activity and reward. Unlike the responses of midbrain dopamine neurons, unpredicted food reward and reward-predictive cues evoked a phasic increase in dopamine that was subregion specific. In rats with limited experience, unpredicted food reward evoked an increase exclusively in the Core. In rats trained on a discriminative stimulus paradigm, both unpredicted reward and reward-predictive cues evoked robust phasic dopamine in the Core and DMS. Thus, phasic dopamine release in select target structures is dynamic and dependent on context and experience. Because the four subregions assayed receive different inputs and have differential projection targets, the regional selectivity of phasic changes in dopamine has important implications for information flow through the striatum and plasticity that underlies learning and goal-directed behavior. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  14. Inability to acquire spatial information and deploy spatial search strategies in mice with lesions in dorsomedial striatum.

    Science.gov (United States)

    Pooters, Tine; Gantois, Ilse; Vermaercke, Ben; D'Hooge, Rudi

    2016-02-01

    Dorsal striatum has been shown to contribute to spatial learning and memory, but the role of striatal subregions in this important aspect of cognitive functioning remains unclear. Moreover, the spatial-cognitive mechanisms that underlie the involvement of these regions in spatial navigation have scarcely been studied. We therefore compared spatial learning and memory performance in mice with lesions in dorsomedial (DMS) and dorsolateral striatum (DLS) using the hidden-platform version of the Morris water maze (MWM) task. Compared to sham-operated controls, animals with DMS damage were impaired during MWM acquisition training. These mice displayed delayed spatial learning, increased thigmotaxis, and increased search distance to the platform, in the absence of major motor dysfunction, working memory defects or changes in anxiety or exploration. They failed to show a preference for the target quadrant during probe trials, which further indicates that spatial reference memory was impaired in these animals. Search strategy analysis moreover demonstrated that DMS-lesioned mice were unable to deploy cognitively advanced spatial search strategies. Conversely, MWM performance was barely affected in animals with lesions in DLS. In conclusion, our results indicate that DMS and DLS display differential functional involvement in spatial learning and memory. Our results show that DMS, but not DLS, is crucial for the ability of mice to acquire spatial information and their subsequent deployment of spatial search strategies. These data clearly identify DMS as a crucial brain structure for spatial learning and memory, which could explain the occurrence of neurocognitive impairments in brain disorders that affect the dorsal striatum. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Subregion-specific modulation of excitatory input and dopaminergic output in the striatum by tonically activated glycine and GABAA receptors

    Directory of Open Access Journals (Sweden)

    Louise eAdermark

    2011-10-01

    Full Text Available The flow of cortical information through the basal ganglia is a complex spatiotemporal pattern of increased and decreased firing. The striatum is the biggest input nucleus to the basal ganglia and the aim of this study was to assess the role of inhibitory GABAA and glycine receptors in regulating synaptic activity in the dorsolateral (DLS and ventral striatum (nucleus accumbens, nAc. Local field potential recordings from coronal brain slices of juvenile and adult Wistar rats showed that GABAA receptors and strychnine-sensitive glycine receptors are tonically activated and inhibit excitatory input to the DLS and to the nAc. Strychnine-induced disinhibition of glutamatergic transmission was insensitive to the muscarinic receptor inhibitor scopolamine (10 µM, inhibited by the nicotinic acetylcholine receptor antagonist mecamylamine (10 µM and blocked by GABAA receptor inhibitors, suggesting that tonically activated glycine receptors depress excitatory input to the striatum through modulation of cholinergic and GABAergic neurotransmission. As an end-product example of striatal GABAergic output in vivo we measured dopamine release in the DLS and nAc by microdialysis in the awake and freely moving rat. Reversed dialysis of bicuculline (50 μM in perfusate only increased extrasynaptic dopamine levels in the nAc, while strychnine administered locally (200 μM in perfusate decreased dopamine output by 60% in both the DLS and nAc. Our data suggest that GABAA and glycine receptors are tonically activated and modulate striatal transmission in a partially sub-region specific manner.

  16. The role of the intrinsic cholinergic system of the striatum: What have we learned from TAN recordings in behaving animals?

    Science.gov (United States)

    Apicella, Paul

    2017-09-30

    Cholinergic interneurons provide rich local innervation of the striatum and play an important role in controlling behavior, as evidenced by the variety of movement and psychiatric disorders linked to disrupted striatal cholinergic transmission. Much progress has been made in recent years regarding our understanding of how these interneurons contribute to the processing of information in the striatum. In particular, investigation of the activity of presumed striatal cholinergic interneurons, identified as tonically active neurons or TANs in behaving animals, has pointed to their role in the signaling and learning of the motivational relevance of environmental stimuli. Although the bulk of this work has been conducted in monkeys, several studies have also been carried out in behaving rats, but information remains rather disparate across studies and it is still questionable whether rodent TANs correspond to TANs described in monkeys. Consequently, our current understanding of the function of cholinergic transmission in the striatum is challenged by the rapidly growing, but often confusing literature on the relationship between TAN activity and specific behaviors. As regards the precise nature of the information conveyed by the cholinergic TANs, a recent influential view emphasized that these local circuit neurons may play a special role in the processing of contextual information that is important for reinforcement learning and selection of appropriate actions. This review provides a summary of recent progress in TAN physiology from which it is proposed that striatal cholinergic interneurons are crucial elements for flexible switching of behaviors under changing environmental conditions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Study on microstructure of corpus striatum in patients with idiopathic rapid eye movement sleep behavior disorder using magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Ya-meng ZHANG

    2017-07-01

    Full Text Available Objective To investigate the structure of corpus striatum and the integrity of white matter fiber in patients with Parkinson's disease (PD and idiopathic rapid eye movement sleep behavior disorder (iRBD.  Methods Twelve patients with iRBD, 12 patients with PD and 10 healthy subjects that were well matched in gender, age and education were enrolled in this study. Head MRI examination was performed to all subjects to observe the changes of corpus striatum structure (the gray matter volume and the integrity of white matter fiber [fractional anisotropy (FA] by combining voxel?based morphometry (VBM and diffusion tensor imaging (DTI.  Results Compared with healthy subjects, the gray matter volume of left caudate nucleus was significantly decreased (P < 0.005, and FA values of left caudate nucleus (P < 0.005, right caudate nucleus (P < 0.001 and right putamen (P < 0.05 were all significantly reduced in iRBD patients; FA value of right putamen was significantly decreased in PD patients (P < 0.05. Compared with PD patients, the gray matter volume of left caudate nucleus of iRBD patients was significantly reduced (P < 0.001, FA values of left caudate nucleus (P < 0.01 and right caudate nucleus (P < 0.005 of iRBD patients were significantly reduced.  Conclusions There is atrophy of gray matter volume and extensive white matter fiber impairment in corpus striatum of patients with iRBD, and the white matter fiber impairment was similar to PD, which provides an anatomical evidence for iRBD being presymptom of PD. DOI: 10.3969/j.issn.1672-6731.2017.05.008

  18. Effects of co-administration of ketamine and ethanol on the dopamine system via the cortex-striatum circuitry.

    Science.gov (United States)

    Liu, Qing; Xu, Tian-Yong; Zhang, Zhi-Bi; Leung, Chi-Kwan; You, Ding-Yun; Wang, Shang-Wen; Yi, Shuai; Jing, Qiang; Xie, Run-Fang; Li, Huifang-Jie; Zeng, Xiao-Feng

    2017-06-15

    Ketamine and ethanol are increasingly being used together as recreational drugs in rave parties. Their effects on the dopamine (DA) system remain largely unknown. This study aimed to investigate the effects of consuming two different concentrations of ketamine with and without alcohol on the DA system. We employed the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of the combined administration of two different doses of ketamine (30mg/kg and 60mg/kg) with ethanol (0.3156g/kg). We evaluated the effects of the combined drug treatment on the transcriptional output of tyrosine hydroxylase (TH), dopa decarboxylase (DDC), synaptosomal-associated protein 25 (SNAP25), and vesicular monoamine transporter 2 (VMAT2) as well as protein expression level of brain-derived neurotrophic factor (BDNF) in rat prefrontal cortex (PFC) and striatum. We found that rats exhibited a dose-dependent, drug-paired, place preference to ketamine and ethanol associated with an elevated DA level in the striatum but not in the PFC. Moreover, treatment involving low- or high-dose ketamine with or without ethanol caused a differential regulatory response in the mRNA levels of the four DA metabolism genes and the cellular protein abundance of BDNF via the cortex-striatum circuitry. This study investigated the molecular mechanisms that occur following the combined administration of ketamine and ethanol in the DA system, which could potentially lead to alterations in the mental status and behavior of ketamine/ethanol users. Our findings may aid the development of therapeutic strategies for substance abuse patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli

    Directory of Open Access Journals (Sweden)

    Lanuza Enrique

    2007-11-01

    Full Text Available Abstract Background Vertebrates sense chemical stimuli through the olfactory receptor neurons whose axons project to the main olfactory bulb. The main projections of the olfactory bulb are directed to the olfactory cortex and olfactory amygdala (the anterior and posterolateral cortical amygdalae. The posterolateral cortical amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly minor outputs are directed to the ventral striatum, in particular to the olfactory tubercle and the islands of Calleja. Results Although the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with the aim of delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus in our own material. Injection of dextran-amines into the posterolateral cortical amygdaloid nucleus of rats resulted in anterograde labeling in the ventral striatum, in particular in the core of the nucleus accumbens, and in the medial olfactory tubercle including some islands of Calleja and the cell bridges across the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were performed to allow retrograde confirmation of these projections. Conclusion The present results extend previous descriptions of the posterolateral cortical amygdaloid nucleus efferent projections, which are mainly directed to the core of the nucleus accumbens and the medial olfactory tubercle. Our data indicate that the projection to the core of the nucleus accumbens arises from layer III; the projection to the olfactory tubercle arises from layer II and is much more robust than previously thought. This latter projection is directed to the medial olfactory tubercle including the corresponding islands of Calleja, an area recently described as critical node for the neural circuit of addiction to some stimulant drugs of abuse.

  20. Functional relationships between the hippocampus and dorsomedial striatum in learning a visual scene-based memory task in rats.

    Science.gov (United States)

    Delcasso, Sébastien; Huh, Namjung; Byeon, Jung Seop; Lee, Jihyun; Jung, Min Whan; Lee, Inah

    2014-11-19

    The hippocampus is important for contextual behavior, and the striatum plays key roles in decision making. When studying the functional relationships with the hippocampus, prior studies have focused mostly on the dorsolateral striatum (DLS), emphasizing the antagonistic relationships between the hippocampus and DLS in spatial versus response learning. By contrast, the functional relationships between the dorsomedial striatum (DMS) and hippocampus are relatively unknown. The current study reports that lesions to both the hippocampus and DMS profoundly impaired performance of rats in a visual scene-based memory task in which the animals were required to make a choice response by using visual scenes displayed in the background. Analysis of simultaneous recordings of local field potentials revealed that the gamma oscillatory power was higher in the DMS, but not in CA1, when the rat performed the task using familiar scenes than novel ones. In addition, the CA1-DMS networks increased coherence at γ, but not at θ, rhythm as the rat mastered the task. At the single-unit level, the neuronal populations in CA1 and DMS showed differential firing patterns when responses were made using familiar visual scenes than novel ones. Such learning-dependent firing patterns were observed earlier in the DMS than in CA1 before the rat made choice responses. The present findings suggest that both the hippocampus and DMS process memory representations for visual scenes in parallel with different time courses and that flexible choice action using background visual scenes requires coordinated operations of the hippocampus and DMS at γ frequencies. Copyright © 2014 the authors 0270-6474/14/3415534-14$15.00/0.

  1. Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.

    Directory of Open Access Journals (Sweden)

    Atsushi Tamura

    Full Text Available The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+ signaling. To characterize Ca(2+ signaling in striatal cells, spontaneous cytoplasmic Ca(2+ transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP in the astrocytes. In both the GFP-negative cells (putative-neurons and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+ transients (referred to as slow Ca(2+ oscillations, which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+ oscillation. Depletion of the intracellular Ca(2+ store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+ oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+ oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+ oscillation in both putative-neurons and astrocytes. The slow Ca(2+ oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+ oscillation may involve in the neuron-glia interaction in the striatum.

  2. Effects of Deltamethrin on striatum and hippocampus mitochondrial integrity and the protective role of Quercetin in rats.

    Science.gov (United States)

    Gasmi, Salim; Rouabhi, Rachid; Kebieche, Mohamed; Boussekine, Samira; Salmi, Aya; Toualbia, Nadjiba; Taib, Chahinez; Bouteraa, Zina; Chenikher, Hajer; Henine, Sara; Djabri, Belgacem

    2017-07-01

    The present work is to evaluate the neurotoxicity induced by pyrethroid insecticide "Deltamethrin" at 0.32 mg/kg/day in two main regions of the Wistar rat brain (hippocampus and striatum) and the protective effects of Quercetin at 10 mg/kg/day on this toxicity after 90 days of exposure. The assay of brain parameters showed that Deltamethrin caused a significant increase of mitochondrial metabolite level (proteins, lipids, and carbohydrates) and enzyme activity (glutathione S-transferase and superoxide dismutase); a decreased amount of mitochondrial glutathione level and catalase and glutathione peroxidase activities; and an increase of malondialdehyde (MDA) acid levels of the two regions. Furthermore, mitochondrial functional testing in the brains of treated rats exhibited a significant increase in permeability followed by a mitochondrial swelling. Instead, a statistically significant decrease in mitochondrial respiration (O 2 consumption) was recorded in the striatum and hippocampus. Our study showed that the pesticide caused a significant increase of the cytochrome c amount correlated with activation of neuronal apoptosis mechanisms by the significant increase of caspase-3 of hippocampus and striatum. In particular, the results of behavioral tests (open field, classic maze tests of sucrose, and Morris water maze) have significant changes, namely bad behavior of the treated rats, affecting the level of anxiety, learning, and memory, and general motor activity has mainly been shown in treated rats. In addition, the histological cuts clearly confirm cerebral necrosis in the hippocampus and the striatum caused by the pesticide. They allow us to consider the necrotic areas, black spots, reduction, and denaturation of these brain regions in the treated rats. On the other hand, we have studied the protective effects against the neurotoxicity of Deltamethrin (DLM). In this context, after the gavage of Quercetin at the dose of 10 mg/kg/day, we have noticed an

  3. Editing for an AMPA receptor subunit RNA in prefrontal cortex and striatum in Alzheimer's disease, Huntington's disease and schizophrenia

    Science.gov (United States)

    Akbarian, S.; Smith, M. A.; Jones, E. G.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    Animal studies and cell culture experiments demonstrated that posttranscriptional editing of the transcript of the GluR-2 gene, resulting in substitution of an arginine for glutamine in the second transmembrane region (TM II) of the expressed protein, is associated with a reduction in Ca2+ permeability of the receptor channel. Thus, disturbances in GluR-2 RNA editing with alteration of intracellular Ca2+ homeostasis could lead to neuronal dysfunction and even neuronal degeneration. The present study determined the proportions of edited and unedited GluR-2 RNA in the prefrontal cortex of brains from patients with Alzheimer's disease, in the striatum of brains from patients with Huntington's disease, and in the same areas of brains from age-matched schizophrenics and controls, by using reverse transcriptase-polymerase chain reaction, restriction endonuclease digestion, gel electrophoresis and scintillation radiometry. In the prefrontal cortex of controls, RNA molecules were unedited and > 99.9% were edited; in the prefrontal cortex both of schizophrenics and of Alzheimer's patients approximately 1.0% of all GluR-2 RNA molecules were unedited and 99% were edited. In the striatum of controls and of schizophrenics, approximately 0.5% of GluR-2 RNA molecules were unedited and 99.5% were edited; in the striatum of Huntington's patients nearly 5.0% of GluR-2 RNA was unedited. In the prefrontal white matter of controls, approximately 7.0% of GluR-2 RNA was unedited. In the normal human prefrontal cortex and striatum, the large majority of GluR-2 RNA molecules contains a CGG codon for arginine in the TMII coding region; this implies that the corresponding AMPA receptors have a low Ca2+ permeability, as previously demonstrated for the rat brain. The process of GluR-2 RNA editing is compromised in a region-specific manner in schizophrenia, in Alzheimer's disease and Huntington's Chorea although in each of these disorders there is still a large excess of edited GluR-2 RNA

  4. The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance

    DEFF Research Database (Denmark)

    Innocenti, Giorgio M.; Dyrby, Tim Bjørn; Andersen, Kasper Winther

    2017-01-01

    -striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported......, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4–0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon...

  5. Estradiol alters Fos-immunoreactivity in the hippocampus and dorsal striatum during place and response learning in middle-aged but not young adult female rats.

    Science.gov (United States)

    Pleil, Kristen E; Glenn, Melissa J; Williams, Christina L

    2011-03-01

    Evidence from lesion and inactivation studies suggests that the hippocampus (HPC) and dorsal striatum compete for control over navigation behavior, and there is some evidence in males that the structure with greater relative activation controls behavior. Estradiol has been shown to enhance HPC-dependent place learning and impair dorsal striatum-dependent response learning in female rats, possibly by increasing hippocampal activation and/or decreasing striatal activation. We used Fos-immunoreactivity (Fos-IR) to examine the activation of several subregions of the HPC and striatum in ovariectomized female rats with or without estradiol replacement 30 min after place or response learning. In 4-month-old rats, neither task nor estradiol increased Fos-IR above explore control levels in any subregion analyzed, even though estradiol impaired response learning. In 12-month-old rats, estradiol increased Fos-IR in the dentate gyrus, dorsal medial striatum, and dorsal lateral striatum in place task learners, while the absence of estradiol increased Fos-IR in these regions in response task learners. However, learning rate was not affected by estradiol in either task. We also included a group of long-term ovariectomized 12-month-old rats that displayed impaired place learning and altered Fos-IR in CA1 of the HPC. These results suggest that task-specific effects of estradiol on hippocampal and striatal activation emerge across age but that relative hippocampal and striatal activation are not related to learning rate during spatial navigation learning.

  6. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  7. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    International Nuclear Information System (INIS)

    Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

    2001-01-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  8. The effects of serotonergic and dopaminergic lesions on sodium-sensitive [3H]mazindol binding in rat hypothalamus and corpus striatum.

    Science.gov (United States)

    Angel, I; Janowsky, A; Paul, S M

    1989-12-04

    The effects of intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-DHT) on sodium-sensitive [3H]mazindol binding were investigated in the rat hypothalamus and corpus striatum. In the hypothalamus, specific [3H]mazindol binding was inhibited by low concentrations of sodium and stimulated by high-sodium concentrations, whereas in the corpus striatum, only a sodium-dependent stimulation of [3H]mazindol binding was observed. Lesions with 6-OHDA significantly reduced sodium-dependent [3H]mazindol binding in the corpus striatum, but had no effect on the binding of [3H]mazindol in the absence of sodium. Lesions of serotonergic neurons with 5,7-DHT, however, had no effect on [3H]mazindol binding in the striatum, but resulted in a significant increase in the number of [3H]mazindol binding sites in the hypothalamus. These data suggest that [3H]mazindol may bind to two anatomically distinct binding sites, one that is stimulated and the other inhibited by sodium. The sodium-stimulated binding sites appear to be located on dopaminergic terminals in the striatum, and in the hypothalamus, the sodium-inhibited sites appear to be regulated by serotonergic neuronal activity.

  9. Altered Neuronal Dynamics in the Striatum on the Behavior of Huntingtin Interacting Protein 14 (HIP14 Knockout Mice

    Directory of Open Access Journals (Sweden)

    Ana María Estrada-Sánchez

    2013-11-01

    Full Text Available Huntington’s disease (HD, a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, impairs information processing in the striatum, which, as part of the basal ganglia, modulates motor output. Growing evidence suggests that huntingtin interacting protein 14 (HIP14 contributes to HD neuropathology. Here, we recorded local field potentials (LFPs in the striatum as HIP14 knockout mice and wild-type controls freely navigated a plus-shaped maze. Upon entering the choice point of the maze, HIP14 knockouts tend to continue in a straight line, turning left or right significantly less often than wild-types, a sign of motor inflexibility that also occurs in HD mice. Striatal LFP activity anticipates this difference. In wild-types, the power spectral density pattern associated with entry into the choice point differs significantly from the pattern immediately before entry, especially at low frequencies (≤13 Hz, whereas HIP14 knockouts show no change in LFP activity as they enter the choice point. The lack of change in striatal activity may explain the turning deficit in the plus maze. Our results suggest that HIP14 plays a critical role in the aberrant behavioral modulation of striatal neuronal activity underlying motor inflexibility, including the motor signs of HD.

  10. Comparative study of D2 receptors and content of DA in striatum before and after electro-acupuncture treatment

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    1999-01-01

    Objective: To evaluate the change of D 2 receptors and its relationship with DA content in experimental hemi-parkinsonism rats before and after electron-acupuncture treatment. Methods: 125 I-IBZM D 2 receptor cerebral autoradiographic analysis, HPLC-ECD DA and its metabolites, homovanillic acid (HVA), 3,4-di-hydroxyphenylacetic acid (DOPAC) content detection were used to study in striatum in before treatment, electro-acupuncture treatment and treatment control group. Results: 1) The DA, HVA and DOPAC level in striatum of lesioned side in electro-acupuncture group was increased comparing with the before treatment and treatment control group (P 125 I-IBZM uptake ratio was 8.04 +- 0.71, (29.34 +- 4.83)% more than that of the contralateral side, but no significant difference was observed as compared with that of the pretreatment group [(8.09 +- 0.52), P>0.05]; however it was much lower than that of the treatment control group (8.61 +- 0.63), P 2 receptors' up regulation in rats with experimental hemi-parkinsonism

  11. Mechanisms of Neuroplasticity and Ethanol's Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis.

    Science.gov (United States)

    Lovinger, David M; Kash, Thomas L

    2015-01-01

    Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction.Two brain regions subject to alcohol's effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol's actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder.

  12. No differences in ventral striatum responsivity between adolescents with a positive family history of alcoholism and controls.

    Science.gov (United States)

    Müller, Kathrin U; Gan, Gabriela; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Ströhle, Andreas; Struve, Maren; Schumann, Gunter; Smolka, Michael N

    2015-05-01

    Individuals with alcohol-dependent parents show an elevated risk of developing alcohol-related problems themselves. Modulations of the mesolimbic reward circuit have been postulated as a pre-existing marker of alcoholism. We tested whether a positive family history of alcoholism is correlated with ventral striatum functionality during a reward task. All participants performed a modified version of the monetary incentive delay task while their brain responses were measured with functional magnetic resonance imaging. We compared 206 healthy adolescents (aged 13-15) who had any first- or second-degree relative with alcoholism to 206 matched controls with no biological relative with alcoholism. Reward anticipation as well as feedback of win recruited the ventral striatum in all participants, but adolescents with a positive family history of alcoholism did not differ from their matched peers. Also we did not find any correlation between family history density and reward anticipation or feedback of win. This finding of no differences did not change when we analyzed a subsample of 77 adolescents with at least one parent with alcohol use disorder and their matched controls. Because this result is in line with another study reporting no differences between children with alcohol-dependent parents and controls at young age, but contrasts with studies of older individuals, one might conclude that at younger age the effect of family history has not yet exerted its influence on the still developing mesolimbic reward circuit. © 2014 Society for the Study of Addiction.

  13. Gene profiling the response to repeated cocaine self-administration in dorsal striatum: a focus on circadian genes.

    Science.gov (United States)

    Lynch, Wendy J; Girgenti, Matthew J; Breslin, Florence J; Newton, Samuel S; Taylor, Jane R

    2008-06-05

    Alterations in gene expression in the dorsal striatum caused by chronic cocaine exposure have been implicated in the long-term behavioral changes associated with cocaine addiction. To gain further insight into the molecular alterations that occur as a result of cocaine self-administration, we conducted a microarray analysis of gene expression followed by bioinformatic gene network analysis that allowed us to identify adaptations at the level of gene expression as well as into interconnected networks. Changes in gene expression were examined in the dorsal striatum of rats 1 day after they had self-administered cocaine for 7 days under a 24-h access, discrete trial paradigm (averaging 98 mg/kg/day). Here we report the regulation of the circadian genes Clock, Bmal1, Cryptochrome1, Period2, as well as several genes that are regulated by/associated with the circadian system (i.e., early growth response 1, dynorphin). We also observed regulation of other relevant genes (i.e., Nur77, beta catenin). These changes were then linked to curated pathways and formulated networks which identified circadian rhythm processes as affected by cocaine self-administration. These data strongly suggest involvement of circadian-associated genes in the brain's response to cocaine and may contribute to an understanding of addictive behavior including disruptions in sleep and circadian rhythmicity.

  14. MicroRNA-124 slows down the progression of Huntington′s disease by promoting neurogenesis in the striatum

    Directory of Open Access Journals (Sweden)

    Tian Liu

    2015-01-01

    Full Text Available MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington′s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington′s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Huntington′s disease transgenic mouse in the rotarod test. 5-Bromo-2′-deoxyuridine (BrdU staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was decreased. These findings suggest that microRNA-124 slows down the progression of Huntington′s disease possibly through its important role in neuronal differentiation and survival.

  15. Pentobarbital decreased nitric oxide release in the rat striatum but ketamine increased the release independent of cholinergic regulation.

    Science.gov (United States)

    Kimura-Kuroiwa, Kaori; Adachi, Yushi U; Mimuro, Soichiro; Kawamata, Mikito; Sato, Shigehito; Matsuda, Naoyuki

    2012-01-01

    Pentobarbital (PB) and ketamine (Ket) influence the concentration of neurotransmitters in the brain. PB has been reported to decrease the extracellular nitric oxide (NO) concentration through a decrease in acetylcholine (ACh) release, while Ket has been shown to increase the NO concentration via an increase in ACh release. Here, we investigated effects of PB and Ket on NO release and the relationship between NO and ACh in the rat striatum by in vivo microdialysis experiments. Male Sprague-Dawley rats were used. A microdialysis probe was inserted into the right striatum and perfused with modified Ringer's solution. Samples were collected every 15 min and injected into an HPLC system. The rats were freely moving, and PB and Ket were administered intraperitoneally. Neostigmine (1 and 10 µM) and mecamylamine (100 µM) were added to the perfusate. Calcium and magnesium concentrations were modified for each anesthetic to influence ACh release. PB decreased NO products (NOx) while Ket increased them. While perfusion with neostigmine showed no effect on baseline NOx concentrations, it diminished the PB-induced NOx reduction at low concentrations and abolished it at high concentrations. Magnesium-free perfusion had no effect on baseline NOx concentrations, whereas perfusion at a low magnesium concentration antagonized the PB-induced NOx reduction. Mecamylamine and calcium-free perfusion had no effect on baseline NOx concentrations and Ket-induced NOx increases. PB may decrease NO release through reduction in ACh release, whereas Ket may increase NO release independent of ACh regulation.

  16. The histamine system in human brain. Changes in neurological and psychiatric disorders

    Energy Technology Data Exchange (ETDEWEB)

    Goodchild, R.E

    1999-09-01

    Autoradiographical examination of the distribution of H{sub 1}- and H{sub 3}- histamine receptor subtypes, using [{sup 3}H]-mepyramine and [{sup 3}H]-R-({alpha}) methylhistamine respectively, found high H{sub 1}-receptor binding densities in neocortex, dentate gyrus and basolateral amygdala, with low binding in all subdivisions of the thalamus and other subcortical areas. H{sub 3}-receptor binding was enriched within the nucleus accumbens, globus pallidus and substantia nigra, whilst was low in the hippocampus, subthalamic nucleus, temporal cortex, motor and somatosensory thalamic areas and basolateral amygdala. In situ hybridisation found H{sub 2}-receptor mRNA located in the striatum, thalamus, hippocampal pyramidal cell layer and dentate gyrus, and specific laminae of neocortex. Comparison of autoradiographically determined H{sub 1}-, H{sub 2}- and H{sub 3}-receptor binding densities between normal and pathological cases found significantly decreased (p < 0.005, ANOVA) striatal and pallidal H{sub 3}-receptor binding in Huntington's disease (HD), with unaltered binding in the insular cortex. A significant correlation (p < 0.01) was present between binding in the internal globus pallidus and HD grade. Binding to the striatal H{sub 1}-receptor was increased (p < 0.05, ANOVA) in Parkinson's disease (PD), whilst H{sub 2}- (measured using [{sup 125}I]-iodoaminopotentidine) and H{sub 3}-receptor binding densities were normal in all areas examined. H{sub 1}-receptor binding was also increased in the hippocampus of Lewy-body dementia (DLB) cases (p < 0.05, Students two-tailed T-Test), whilst hippocampal and cortical H{sub 2}-receptor binding densities were decreased in DLB, together with Alzheimer's disease (AD) (p < 0.05, ANOVA). H{sub 3}-receptor binding was increased in the insular cortex and decreased in the temporal cortex of DLB, but not AD, cases (p < 0.05, ANOVA). H{sub 1}-receptor binding to tissue from patients with schizophrenia was

  17. N-methyl-D-aspartate receptor-mediated glutamate transmission in nucleus accumbens plays a more important role than that in dorsal striatum in cognitive flexibility

    Directory of Open Access Journals (Sweden)

    Xuekun eDing

    2014-09-01

    Full Text Available Cognitive flexibility is a critical ability for adapting to an ever-changing environment in humans and animals. Deficits in cognitive flexibility are observed in most schizophrenia patients. Previous studies reported that the medial prefrontal cortex-to-ventral striatum and orbital frontal cortex-to-dorsal striatum circuits play important roles in extra- and intra-dimensional strategy switching, respectively. However, the precise function of striatal subregions in flexible behaviors is still unclear. N-methyl-D-aspartate receptors (NMDARs are major glutamate receptors in the striatum that receive glutamatergic projections from the frontal cortex. The membrane insertion of Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs depends on NMDAR activation and is required in learning and memory processes. In the present study, we measured set-shifting and reversal learning performance in operant chambers in rats and assessed the effects of blocking NMDARs and Ca2+-permeable AMPARs in striatal subregions on behavioral flexibility. The blockade of NMDARs in the nucleus accumbens (NAc core by AP5 impaired set-shifting ability by causing a failure to modify prior learning. The suppression of NMDAR-mediated transmission in the NAc shell induced a deficit in set-shifting by disrupting the learning and maintenance of novel strategies. During reversal learning, infusions of AP5 into the NAc shell and core impaired the ability to learn and maintain new strategies. However, behavioral flexibility was not significantly affected by blocking NMDARs in the dorsal striatum. We also found that the blockade of Ca2+-permeable AMPARs by NASPM in any subregion of the striatum did not affect strategy switching. These findings suggest that NMDAR-mediated glutamate transmission in the NAc contributes more to cognitive execution compared with the dorsal striatum.

  18. Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

    Science.gov (United States)

    Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

    2016-02-01

    We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

  19. Manganese-Disrupted Interaction of Dopamine D1 and NMDAR in the Striatum to Injury Learning and Memory Ability of Mice.

    Science.gov (United States)

    Song, Qifan; Deng, Yu; Yang, Xinxin; Bai, Ying; Xu, Bin; Liu, Wei; Zheng, Wenxue; Wang, Can; Zhang, Meng; Xu, Zhaofa

    2016-12-01

    Manganese (Mn) is widely regarded as a neurotoxic heavy metal that causes learning and memory deficits. Recently, it has been proved that the striatum is related to memory and learning ability. However, no previous study focused on the effect of Mn-induced learning and memory deficits on the striatum. This study aims to investigate the probable interaction of dopamine D1 receptor (DR1) and N-methyl-D-aspartate receptor (NMDAR), two cognition-related receptors in the striatum during Mn exposure. Mice are randomly divided into four groups, including control group, 12.5 mg/kg MnCl 2 group, 25 mg/kg MnCl 2 group, and 50 mg/kg MnCl 2 group. The mice receive intraperitoneal injections of 0, 12.5, 25, and 50 mg/kg MnCl 2 once daily for 2 weeks. Then, learning and memory ability, pathological changes, expression, and interaction of DR1 and NMDAR are determined. It has been found that Mn disrupted spatial learning and memory ability of mice by Morris water maze test and the passive avoidance test. Pathological and ultrastructure were injured. Mn decreased the immunohistochemical activities, protein levels, and messenger RNA (mRNA) expression of DR1, NR1, and NR2A. Mn exposure inhibited interaction between DR1 and NMDAR in striatum by double immunofluorescent staining and co-immunoprecipitation. In conclusion, our study illustrated that Mn caused learning and memory dysfunction via injury of striatum and inhibition of interaction between DR1 and NMDAR in striatum.

  20. Protective Effect of Curcumin by Modulating BDNF/DARPP32/CREB in Arsenic-Induced Alterations in Dopaminergic Signaling in Rat Corpus Striatum.

    Science.gov (United States)

    Srivastava, Pranay; Dhuriya, Yogesh K; Gupta, Richa; Shukla, Rajendra K; Yadav, Rajesh S; Dwivedi, Hari N; Pant, Aditya B; Khanna, Vinay K

    2018-01-01

    Earlier, protective role of curcumin in arsenic-induced dopamine (DA)-D2 receptor dysfunctions in corpus striatum has been demonstrated by us. In continuation to that, the present study is focused to decipher the molecular mechanisms associated with alterations in dopaminergic signaling on arsenic exposure in corpus striatum and assess the protective efficacy of curcumin. Exposure to arsenic (20 mg/kg, body weight p.o. for 28 days) in rats resulted to decrease the expression of presynaptic proteins-tyrosine hydroxylase and VMAT2 while no effect was observed on the expression of DAT in comparison to controls. A significant decrease in the expression of DA-D2 receptors associated with alterations in the expression of PKA, pDARPP32 (Thr 34), and PP1 α was clearly evident on arsenic exposure. Expression of BDNF and pGSK3β in corpus striatum was found decreased in arsenic-exposed rats. Simultaneous treatment with curcumin (100 mg/kg, body weight p.o. for 28 days) resulted to protect arsenic-induced alterations in the expression of DA-D2 receptors, PKA, pDARPP32, pCREB, and pPP1α. Neuroprotective efficacy of curcumin can possibly be attributed to its antioxidant potential which significantly protected arsenic-induced mitochondrial dysfunctions by modulating the ROS generation and apoptosis. Modulation in the expression of BDNF and pGSK3β in corpus striatum by curcumin exhibits the importance of neuronal survival pathway in arsenic-induced dopaminergic dysfunctions. Interestingly, curcumin was also found to protect arsenic-induced ultrastructural changes in corpus striatum. The results exhibit that curcumin modulates BDNF/DARPP32/CREB in arsenic-induced alterations in dopaminergic signaling in rat corpus striatum.

  1. The aberrantly expressed long non-coding RNA in the substantia nigra and corpus striatum of Nrf2-knockout mice.

    Science.gov (United States)

    Liu, Jian; Xu, Yali; Kang, Yunxiao; Cao, Shanhu; Shi, Geming; Cui, Huixian; Sun, Shaoguang; Wang, Lei

    2017-10-01

    Nuclear factor erythroid 2 like 2 (Nrf2) functions as a neuroprotective agent in Parkinson's disease (PD). This study aimed to investigate the key long non-coding RNAs (lncRNAs) correlated with Nrf2, which might provide valuable information for the exploration of pathogenesis of PD. The lncRNA and mRNA expression profiling of substantia nigra and corpus striatum of Nrf2 (-/-) mice model was obtained from microarray analysis. The animal experiments conducted for this study were approved by the ethics committee of Hebei Medical University. Bioinformatics analyses were conducted, including differentially expressed lncRNAs/mRNA (differentially expressed lncRNA, DEL/differentially expressed mRNA, DEM) identification, DEL-DEM coexpression network construction, and biological functions prediction. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate abnormally expressed DELs and DEMs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice model. A total of 48 DELs (37 down-regulated and 11 up-regulated) were identified both in Nrf2 (-/-) substantia nigra and corpus striatum; 96 DEMs and 643 DEMs were identified in the substantia nigra and corpus striatum, respectively. DEL-DEM coexpressed network was constructed. LncRNA AK076880, AK036620, and AK020330 had high connectivity with DEMs both in the substantia nigra and corpus striatum. These DEMs were significantly enriched in signaling pathways such as the calcium signaling pathway, Huntington's disease, Alzheimer's disease, mitogen-activated protein kinase (MAPK) signaling pathway, and the Wnt signaling pathway. Generally, qRT-PCR validation results of selected DEMs and DELs were consistent with microarray data. The dysregulated DELs and DEMs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice were identified. Our results might provide useful information for further exploring the pathogenesis mechanism of PD. © 2017 International Society for Neurochemistry.

  2. Oral Administration of Methylphenidate (Ritalin) Affects Dopamine Release Differentially Between the Prefrontal Cortex and Striatum: A Microdialysis Study in the Monkey.

    Science.gov (United States)

    Kodama, Tohru; Kojima, Takashi; Honda, Yoshiko; Hosokawa, Takayuki; Tsutsui, Ken-Ichiro; Watanabe, Masataka

    2017-03-01

    Methylphenidate (MPH; trade name Ritalin) is a widely used drug for the treatment of attention deficit hyperactivity disorder (ADHD) and is often used as a cognitive enhancer. Because MPH increases dopamine (DA) release by blocking the DA transporter in the human striatum, MPH is supposed to work on attention and cognition through a DA increase in the striatum. However, ADHD patients show impaired prefrontal cortex (PFC) function and MPH administration is associated with increased neural activity in the PFC. Although MPH is indicated to increase DA release in the rat PFC, there has been no study to examine MPH-induced DA changes in the human PFC because of technical difficulties associated with the low level of PFC DA receptors. Using the microdialysis technique, we examined the effects of oral administration of MPH on DA release in both the PFC and striatum in the monkey. We also tested the effect of MPH on cognitive task performance. As in human studies, in the striatum, both high and low doses of MPH induced consistent increases in DA release ∼30 min after their administrations. In the PFC, a consistent increase in DA release was observed 1 h after a high dose, but not low doses, of MPH. Low doses of MPH improved cognitive task performance, but a high dose of MPH made the monkey drowsy. Therefore, low-dose MPH-induced cognitive enhancement is supported by striatum DA increase. SIGNIFICANCE STATEMENT Methylphenidate (MPH) is a widely used drug for the treatment of attention deficit hyperactivity disorder and is often used as a cognitive enhancer. Although human positron emission tomography studies suggest that MPH works on attention and cognition through dopamine (DA) changes in the striatum, there has been no study to examine MPH-induced DA changes in the human prefrontal cortex (PFC). Using the microdialysis technique in monkeys, we found, for the first time, that low doses of MPH consistently increased DA release in the striatum but did not in the PFC

  3. Exploration of D2 receptors and content of DA of striatum in hemi-parkinsonism model rats before and after madopar treatment

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    1998-01-01

    125 I-IBZM autoradiographic analysis, HPLC-ECD were used to study the relationship between D 2 receptors and the content of DA, HVA, DOPAC in striatum of hemi-parkinsonism model rats before and after Madopar treatment. After Madopar treatment, the striatum/cerebellum 125 I-IBZM uptake ratio of lesioned side was 7.23 +- 0.67, showed 17.22 +- 3.94% increasing as compared to the contralateral side, the increasing were significantly declined compared with the pretreatment group and control group (P 2 receptors

  4. Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task.

    Directory of Open Access Journals (Sweden)

    Haruna Hirata

    Full Text Available Caspr3 (Contactin-associated protein-like 3, Cntnap3 is a neural cell adhesion molecule belonging to the Caspr family. We have recently shown that Caspr3 is expressed abundantly between the first and second postnatal weeks in the mouse basal ganglia, including the striatum, external segment of the globus pallidus, subthalamic nucleus, and substantia nigra. However, its physiological role remains largely unknown. In this study, we conducted a series of behavioral analyses on Capsr3-knockout (KO mice and equivalent wild-type (WT mice to investigate the role of Caspr3 in brain function. No significant differences were observed in most behavioral traits between Caspr3-KO and WT mice, but we found that Caspr3-KO mice performed poorly during the early phase of the accelerated rotarod task in which latency to falling off a rod rotating with increasing velocity was examined. In the late phase, the performance of the Caspr3-KO mice caught up to the level of WT mice, suggesting that the deletion of Caspr3 caused a delay in motor learning. We then examined changes in neural activity after training on the accelerated rotarod by conducting immunohistochemistry using antibody to c-Fos, an indirect marker for neuronal activity. Experience of the accelerated rotarod task caused increases in the number of c-Fos-positive cells in the dorsal striatum, cerebellum, and motor cortex in both Caspr3-KO and WT mice, but the number of c-Fos-positive cells was significantly lower in the dorsal striatum of Caspr3-KO mice than in that of WT mice. The expression of c-Fos in the ventral striatum of Caspr3-KO and WT mice was not altered by the training. Our findings suggest that reduced activation of neural cells in the dorsal striatum in Caspr3-KO mice leads to a decline in motor learning in the accelerated rotarod task.

  5. Neuronal activity (c-Fos delineating interactions of the cerebral cortex and basal ganglia

    Directory of Open Access Journals (Sweden)

    Mei-Hong eQiu

    2014-03-01

    Full Text Available The cerebral cortex and basal ganglia (BG form a neural circuit that is disrupted in disorders such as Parkinson’s disease. We found that neuronal activity (c-Fos in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave EEG but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine (NMDA receptor antagonist and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist. Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN input to internal globus pallidus (GPi and substantia nigra pars reticulata (SNr, while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe, and STN but increased activity of the GPi, SNr and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders.

  6. The histamine system in human brain. Changes in neurological and psychiatric disorders

    International Nuclear Information System (INIS)

    Goodchild, R.E.

    1999-09-01

    Autoradiographical examination of the distribution of H 1 - and H 3 - histamine receptor subtypes, using [ 3 H]-mepyramine and [ 3 H]-R-(α) methylhistamine respectively, found high H 1 -receptor binding densities in neocortex, dentate gyrus and basolateral amygdala, with low binding in all subdivisions of the thalamus and other subcortical areas. H 3 -receptor binding was enriched within the nucleus accumbens, globus pallidus and substantia nigra, whilst was low in the hippocampus, subthalamic nucleus, temporal cortex, motor and somatosensory thalamic areas and basolateral amygdala. In situ hybridisation found H 2 -receptor mRNA located in the striatum, thalamus, hippocampal pyramidal cell layer and dentate gyrus, and specific laminae of neocortex. Comparison of autoradiographically determined H 1 -, H 2 - and H 3 -receptor binding densities between normal and pathological cases found significantly decreased (p 3 -receptor binding in Huntington's disease (HD), with unaltered binding in the insular cortex. A significant correlation (p 1 -receptor was increased (p 2 - (measured using [ 125 I]-iodoaminopotentidine) and H 3 -receptor binding densities were normal in all areas examined. H 1 -receptor binding was also increased in the hippocampus of Lewy-body dementia (DLB) cases (p 2 -receptor binding densities were decreased in DLB, together with Alzheimer's disease (AD) (p 3 -receptor binding was increased in the insular cortex and decreased in the temporal cortex of DLB, but not AD, cases (p 1 -receptor binding to tissue from patients with schizophrenia was significantly reduced in all cortical (p 2 -receptor binding was unaltered in all areas, however H 3 -receptor binding was increased in the posterior putamen (p < 0.05), and highly significantly decreased (p < 0.005, Students two-tailed T-Test) in the external globus pallidus in schizophrenia. (author)

  7. The Arbitration–Extension Hypothesis: A Hierarchical Interpretation of the Functional Organization of the Basal Ganglia

    Science.gov (United States)

    Kamali Sarvestani, Iman; Lindahl, Mikael; Hellgren-Kotaleski, Jeanette; Ekeberg, Örjan

    2011-01-01

    Based on known anatomy and physiology, we present a hypothesis where the basal ganglia motor loop is hierarchically organized in two main subsystems: the arbitration system and the extension system. The arbitration system, comprised of the subthalamic nucleus, globus pallidus, and pedunculopontine nucleus, serves the role of selecting one out of several candidate actions as they are ascending from various brain stem motor regions and aggregated in the centromedian thalamus or descending from the extension system or from the cerebral cortex. This system is an action-input/action-output system whose winner-take-all mechanism finds the strongest response among several candidates to execute. This decision is communicated back to the brain stem by facilitating the desired action via cholinergic/glutamatergic projections and suppressing conflicting alternatives via GABAergic connections. The extension system, comprised of the striatum and, again, globus pallidus, can extend the repertoire of responses by learning to associate novel complex states to certain actions. This system is a state-input/action-output system, whose organization enables it to encode arbitrarily complex Boolean logic rules using striatal neurons that only fire given specific constellations of inputs (Boolean AND) and pallidal neurons that are silenced by any striatal input (Boolean OR). We demonstrate the capabilities of this hierarchical system by a computational model where a simulated generic “animal” interacts with an environment by selecting direction of movement based on combinations of sensory stimuli, some being appetitive, others aversive or neutral. While the arbitration system can autonomously handle conflicting actions proposed by brain stem motor nuclei, the extension system is required to execute learned actions not suggested by external motor centers. Being precise in the functional role of each component of the system, this hypothesis generates several readily testable

  8. Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using 18F-FDG

    International Nuclear Information System (INIS)

    Kim, J.H.; Son, Y.D.; Kim, H.K.; Oh, C.H.; Kim, J.M.; Kim, Y.B.; Lee, C.

    2018-01-01

    Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using 18 F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using 18 F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

  9. Interregional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using 18F-FDG.

    Science.gov (United States)

    Kim, J H; Son, Y D; Kim, J M; Kim, H K; Kim, Y B; Lee, C; Oh, C H

    2017-11-13

    Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an interregional correlation analysis of the 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using 18F-FDG. For detailed interregional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the interregional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using 18F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders.

  10. Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using {sup 18}F-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H. [Research Institute for Advanced Industrial Technology, Korea University, Sejong (Korea, Republic of); Son, Y.D.; Kim, H.K.; Oh, C.H., E-mail: ohch@korea.ac.kr [College of Health Science, Gachon University, Incheon, (Korea, Republic of); Kim, J.M. [College of Science and Technology, Korea University, Sejong (Korea, Republic of); Kim, Y.B. [Gachon University School of Medicine, Incheon (Korea, Republic of); Lee, C. [Bioimaging Research Team, Korea Basic Science Institute, Cheongju (Korea, Republic of)

    2018-02-01

    Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using {sup 18}F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using {sup 18}F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

  11. The neuroprotective agent CNTF decreases neuronal metabolites in the rat striatum: an in vivo multimodal magnetic resonance imaging study

    Science.gov (United States)

    Carrillo-de Sauvage, Maria-Angeles; Flament, Julien; Bramoulle, Yann; Ben Haim, Lucile; Guillermier, Martine; Berniard, Aurélie; Aurégan, Gwennaëlle; Houitte, Diane; Brouillet, Emmanuel; Bonvento, Gilles; Hantraye, Philippe; Valette, Julien; Escartin, Carole

    2015-01-01

    Ciliary neurotrophic factor (CNTF) is neuroprotective against multiple pathologic conditions including metabolic impairment, but the mechanisms are still unclear. To delineate CNTF effects on brain energy homeostasis, we performed a multimodal imaging study, combining in vivo proton magnetic resonance spectroscopy, high-performance liquid chromatography analysis, and in situ glutamate imaging by chemical exchange saturation transfer. Unexpectedly, we found that CNTF expression through lentiviral gene transfer in the rat striatum significantly decreased the levels of neuronal metabolites (N-acetyl-aspartate, N-acetyl-aspartyl-glutamate, and glutamate). This preclinical study shows that CNTF remodels brain metabolism, and suggests that decreased levels of neuronal metabolites may occur in the absence of neuronal dysfunction. PMID:25833344

  12. Volatiles and Antimicrobial Activity of the Essential Oils of the Mosses Pseudoscleropodiumpurum, Eurhynchium striatum, and Eurhynchium angustirete Grown in Turkey

    Directory of Open Access Journals (Sweden)

    Gonca Tosun

    2015-01-01

    Full Text Available The chemical composition of the essential oils from all parts of Pseudoscleropodium purum , Eurhynchium striatum and Eurhynchium angustirete were analysed by GC-FID-MS. Sixty-five, thirty-four and seven compounds, accounting for 99.7%, 97.3% and 99.9% of the oils, were identified and the main components were a - pinene (16.1%, 3-octanone (48.1%, and eicosane (28.6%, respectively. The essential oils were also tested against nine strains using a broth microdilution method and showed moderate antimicrobial activity with minimum inhibitory concentrations (MIC ranging from 278.2 to 2225 µg/mL. All the mosses essential oils showed good antituberculosis activity against Mycobacterium smegmatis with MIC of 278.2-312.0 µg/mL.

  13. Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum

    DEFF Research Database (Denmark)

    Deserno, Lorenz; Beck, Anne; Huys, Quentin J. M.

    2015-01-01

    -drug-related stimuli towards drug-related stimuli. Such ‘hijacked’ dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs......Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non......) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N = 27). All participants also underwent 6-[18F]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation...

  14. Muscarinic receptor/G-protein coupling is reduced in the dorsomedial striatum of cognitively impaired aged rats.

    Science.gov (United States)

    Nieves-Martinez, Erasmo; Haynes, Kathryn; Childers, Steven R; Sonntag, William E; Nicolle, Michelle M

    2012-02-01

    Behavioral flexibility, the ability to modify responses due to changing task demands, is detrimentally affected by aging with a shift towards increased cognitive rigidity. The neurobiological basis of this cognitive deficit is not clear although striatal cholinergic neurotransmission has been implicated. To investigate the possible association between striatal acetylcholine signaling with age-related changes in behavioral flexibility, young, middle-aged, and aged F344 X Brown Norway F1 rats were assessed using an attentional set-shifting task that includes two tests of behavioral flexibility: reversal learning and an extra-dimensional shift. Rats were also assessed in the Morris water maze to compare potential fronto-striatal-dependent deficits with hippocampal-dependent deficits. Behaviorally characterized rats were then assessed for acetylcholine muscarinic signaling within the striatum using oxotremorine-M-stimulated [(35)S]GTPγS binding and [(3)H]AFDX-384 receptor binding autoradiography. The results showed that by old age, cognitive deficits were pronounced across cognitive domains, suggesting deterioration of both hippocampal and fronto-striatal regions. A significant decline in oxotremorine-M-stimulated [(35)S]GTPγS binding was limited to the dorsomedial striatum of aged rats when compared to young and middle-aged rats. There was no effect of age on striatal [(3)H]AFDX-384 receptor binding. These results suggest that a decrease in M2/M4 muscarinic receptor coupling is involved in the age-associated decline in behavioral flexibility. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Ecto-ATPase inhibition: ATP and adenosine release under physiological and ischemic in vivo conditions in the rat striatum.

    Science.gov (United States)

    Melani, Alessia; Corti, Francesca; Stephan, Holger; Müller, Christa E; Donati, Chiara; Bruni, Paola; Vannucchi, Maria Giuliana; Pedata, Felicita

    2012-01-01

    In the central nervous system (CNS) ATP and adenosine act as transmitters and neuromodulators on their own receptors but it is still unknown which part of extracellular adenosine derives per se from cells and which part is formed from the hydrolysis of released ATP. In this study extracellular concentrations of adenosine and ATP from the rat striatum were estimated by the microdialysis technique under in vivo physiological conditions and after focal ischemia induced by medial cerebral artery occlusion. Under physiological conditions, adenosine and ATP concentrations were in the range of 130 nmol/L and 40 nmol/L, respectively. In the presence of the novel ecto-ATPase inhibitor, PV4 (100 nmol/L), the extracellular concentration of ATP increased 12-fold to ~360 nmol/L but the adenosine concentration was not altered. This demonstrates that, under physiological conditions, adenosine is not a product of extracellular ATP. In the first 4h after ischemia, adenosine increased to ~690 nmol/L and ATP to ~50 nmol/L. In the presence of PV4 the extracellular concentration of ATP was in the range of 450 nmol/L and a significant decrease in extracellular adenosine (to ~270 nmol/L) was measured. The contribution of extracellular ATP to extracellular adenosine was maximal in the first 20 min after ischemia onset. Furthermore we demonstrated, by immunoelectron microscopy, the presence of the concentrative nucleoside transporter CNT2 on plasma and vesicle membranes isolated from the rat striatum. These results are in favor that adenosine is transported in vesicles and is released in an excitation-secretion manner under in vivo physiological conditions. Early after ischemia, extracellular ATP is hydrolyzed by ecto-nucleotidases which significantly contribute to the increase in extracellular adenosine. To establish the contribution of extracellular ATP to adenosine might constitute the basis for devising a correct putative purinergic strategy aimed at protection from ischemic damage

  16. Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum.

    Science.gov (United States)

    Gasparotto, Juciano; Ribeiro, Camila Tiefensee; Bortolin, Rafael Calixto; Somensi, Nauana; Fernandes, Henrique Schaan; Teixeira, Alexsander Alves; Guasselli, Marcelo Otavio Rodrigues; Agani, Crepin Aziz Jose O; Souza, Natália Cabral; Grings, Mateus; Leipnitz, Guilhian; Gomes, Henrique Mautone; de Bittencourt Pasquali, Matheus Augusto; Dunkley, Peter R; Dickson, Phillip W; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

    2017-05-01

    Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50μg/kg) was followed after 1h by a single LPS (5mg/kg) intraperitoneal injection. Twenty-four hours later, tissues were isolated for analysis. RAGE antibody reduced LPS-induced inflammatory effects in both serum and liver; the levels of proinflammatory cytokines (TNF-α, IL-1β) were decreased and the phosphorylation/activation of RAGE downstream targets (ERK1/2, IκB and p65) in liver were significantly attenuated. RAGE antibody prevented LPS-induced effects on TNF-α and IL-1β in CSF. In striatum, RAGE antibody inhibited increases in IL-1β, Iba-1, GFAP, phospho-ERK1/2 and phospho-tau (ser202), as well as the decrease in synaptophysin levels. These effects were caused by systemic RAGE inhibition, as RAGE antibody did not cross the blood-brain barrier. RAGE antibody also prevented striatal lipoperoxidation and activation of mitochondrial complex II. In conclusion, blockade of RAGE is able to inhibit inflammatory responses induced by LPS in serum, liver, CSF and brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders.

    Science.gov (United States)

    Haznedar, M Mehmet; Buchsbaum, Monte S; Hazlett, Erin A; LiCalzi, Elizabeth M; Cartwright, Charles; Hollander, Eric

    2006-07-01

    In patients with autism, behavioral deficits as well as neuroimaging studies of the anterior cingulate cortex suggest ventral rather than dorsal striatal and thalamic abnormalities in structure and function. The authors used imaging studies to map volumetric and metabolic differences within the entire dorsoventral extent of the striatum and thalamus. Magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure volumes and metabolic activity in the thalamus, caudate, and putamen in 17 patients with autism or Asperger's disorder and 17 age- and sex-matched comparison subjects. Subjects performed a serial verbal learning test during the [(18)F]-fluorodeoxyglucose uptake period. The regions of interest were outlined on contiguous axial MRI slices. After PET/MRI coregistration, region-of-interest coordinates were applied to the PET scan for each individual. Between-group differences in metabolism were assessed by three-dimensional statistical probability mapping. The patients with autism spectrum disorders had greater volumes of the right caudate nucleus than comparison subjects as well as a reversal of the expected left-greater-than-right hemispheric asymmetry. Patients also had lower relative glucose metabolic rates bilaterally in the ventral caudate, putamen, and thalamus. Patients with autism had lower metabolic activity in the ventral thalamus than those with Asperger's disorder, but they did not differ from comparison subjects in metabolic activity in the caudate nucleus. These results are consistent with a deficit in the anterior cingulate-ventral striatum-anterior thalamic pathway in patients with autism spectrum disorders. The results also suggest an important role for the caudate in helping support working-memory demands.

  18. Interactions between procedural learning and cocaine exposure alter spontaneous and cortically-evoked spike activity in the dorsal striatum

    Directory of Open Access Journals (Sweden)

    Janie eOndracek

    2010-12-01

    Full Text Available We have previously shown that cocaine enhances gene regulation in the sensorimotor striatum associated with procedural learning in a running-wheel paradigm. Here we assessed whether cocaine produces enduring modifications of learning-related changes in striatal neuron activity, using single-unit recordings in anesthetized rats 1 day after the wheel training. Spontaneous and cortically-evoked spike activity was compared between groups treated with cocaine or vehicle immediately prior to the running-wheel training or placement in a locked wheel (control conditions. We found that wheel training in vehicle-treated rats increased the average firing rate of spontaneously active neurons without changing the relative proportion of active to quiescent cells. In contrast, in rats trained under the influence of cocaine, the proportion of spontaneously firing to quiescent cells was significantly greater than in vehicle-treated, trained rats. However, this effect was associated with a lower average firing rate in these spontaneously active cells, suggesting that training under the influence of cocaine recruited additional low-firing cells. Measures of cortically-evoked activity revealed a second interaction between cocaine treatment and wheel training, namely, a cocaine-induced decrease in spike onset latency in control rats (locked wheel. This facilitatory effect of cocaine was abolished when rats trained in the running wheel during cocaine action. These findings highlight important interactions between cocaine and procedural learning, which act to modify population firing activity and the responsiveness of striatal neurons to excitatory inputs. Moreover, these effects were found 24 hours after the training and last drug exposure indicating that cocaine exposure during the learning phase triggers long-lasting changes in synaptic plasticity in the dorsal striatum. Such changes may contribute to the transition from recreational to habitual or compulsive drug

  19. Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease

    Science.gov (United States)

    Sagredo, Onintza; González, Sara; Aroyo, Ilia; Pazos, María Ruth; Benito, Cristina; Lastres-Becker, Isabel; Romero, Juan P.; Tolón, Rosa M.; Mechoulam, Raphael; Brouillet, Emmanuel; Romero, Julián; Fernández-Ruiz, Javier

    2009-01-01

    Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington’s disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions but they are markedly up-regulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labelled with the marker of reactive microglia OX-42, and also in cells labelled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-α (TNF-α) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be up-regulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-α. Altogether our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. PMID:19115380

  20. Radiolabeling of dopamine uptake sites in mouse striatum: comparison of binding sites for cocaine, mazindol, and GBR 12935.

    Science.gov (United States)

    Reith, M E; Selmeci, G

    1992-03-01

    This study addressed the possibility of a unique binding interaction between cocaine and the dopamine transporter as compared with other blockers of dopamine uptake. Cocaine binding sites in a fresh P2 fraction of mouse striatum were labeled with [3H]CFT, a phenyltropane analog of cocaine also known as WIN 35,428, and compared with sites labeled with [3H]mazindol or [3H]GBR 12935. Under the conditions used, homogeneous binding was observed that was inhibited monophasically by cocaine, CFT, and mazindol; the same potencies were observed with the three radioligands. Saturation analysis in the presence and in the absence of unlabeled inhibitor (CFT, mazindol, cocaine) indicated a change in the Kd but not the Bmax, consonant with a competitive mechanisms. Tris-HCl reduced the affinity of each radioligand and unlabeled inhibitor without changing the Bmax. N-Ethylmaleimide reduced the binding of all radioligands equally and cocaine offered protection. The dissociation rate of [3H]CFT and [3H]mazindol binding was not affected by the presence of mazindol and CFT, respectively. The Bmax of [3H]CFT and [3H]mazindol binding was the same; the relatively higher value for [3H]GBR 12935 binding in analyses involving varying tritiated GBR 12935 only, was due primarily to an underestimation of the specific activity of [3H]GBR 12935. All results are in agreement with a one-site model in which cocaine, CFT, mazindol, and GBR 12935 share a common binding site in mouse striatum.

  1. Lipopolysaccharide-induced radical formation in the striatum is abolished in Nox2 gp91phox-deficient mice.

    Science.gov (United States)

    Clement, Hans-Willi; Vazquez, Juan F; Sommer, Olaf; Heiser, Philip; Morawietz, Henning; Hopt, Ulrich; Schulz, Eberhard; von Dobschütz, Ernst

    2010-01-01

    Encephalopathy associated with septic shock as well as psychiatric disorders can be caused by the central nervous formation of reactive oxygen species (ROS) associated with inflammation. The systemic application of lipopolysaccharide (LPS, 100 mug/kg i.p.) also serves as a model for major depression and results in enhanced inflammatory processes. which are characterized by the stimulation of microglia or macrophages that then impair normal brain function. The aim of the present study was to analyze the effect of peripherally applied LPS on the central nervous formation of ROS and IL-6 in wild-type mice and in mice lacking the NADPH oxidase Nox2 subunit gp91phox. Microdialysis was performed in the striatum of the mice. Central nervous ROS were detected by electron spin resonance spectroscopy using 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) as reactant, which was infused via a microdialysis probe. IL-6 was measured in microdialysis samples by an immunoassay. Finally, blood samples were taken by heart puncture to detect IL-6 in plasma. In the wild-type mice, LPS significantly increased the ROS formation in the striatum of wild-type mice and resulted in a significantly enhanced IL-6 production. In the mice lacking the NADPH oxidase Nox2 subunit gp91phox, LPS did not enhance ROS formation, while central IL-6 was significantly increased. IL-6 plasma values were enhanced in both types of mice. In conclusion, the gp91phox-containing NADPH oxidase complex is involved in the central nervous ROS formation after peripheral LPS stimulation and might be a pharmacological target in patients with septic shock.

  2. Regulation of dopamine presynaptic markers and receptors in the striatum of DJ-1 and Pink1 knockout rats

    Science.gov (United States)

    Sun, Jianjun; Kouranova, Evguenia; Cui, Xiaoxia; Mach, Robert H.; Xu, Jinbin

    2014-01-01

    Pathogenic autosomal recessive mutations in the DJ-1 (Park7) or the PTEN-induced putative kinase 1 (Pink1 or PARK6) genes are associated with familial Parkinson’s disease (PD). It is not well known regarding the pathological mechanisms involving the DJ-1 and Pink1 mutations. Here we characterized DJ-1 and Pink1 knockout rats both through expression profiling and using quantitative autoradiography to measure the densities of the dopamine D1, D2, D3 receptors, vesicular monoamine transporter type-2 (VMAT2) and dopamine transporter (DAT) in the striatum of transgenic rats and wild type controls. Expression profiling with a commercially available array of 84 genes known to be involved in PD indicated that only the target gene was significantly downregulated in each transgenic rat model. D1 receptor, VMAT2, and DAT were measured using [3H]SCH23390, [3H]dihydrotetrabenazine, and [3H]WIN35428, respectively. No significant changes were observed in the density of DAT in either model. Although the densities of VMAT2 and D1 receptor were unchanged in Pink1 knockout, but both were increased in DJ-1 knockout rats. The densities of D2 and D3 receptors, determined by mathematical analysis of binding of radioligands [3H]WC-10 and [3H]raclopride, were significantly increased in both knockout models. These distinctive changes in the expression of dopamine presynaptic markers and receptors in the striatum may reflect different compensatory regulation of dopamine system in DJ-1 versus Pink1 knockout rat models of familial PD. PMID:24157858

  3. Differential neurochemical responses of the canine striatum with pentobarbital or ketamine anesthesia: a 3T proton MRS study.

    Science.gov (United States)

    Lee, Sung-Ho; Kim, Sang-Young; Woo, Dong-Cheol; Choe, Bo-Young; Ryu, Kyung-Nam; Choi, Woo-Suk; Jahng, Geon-Ho; Yim, Sung-Vin; Kim, Hwi-Yool; Choi, Chi-Bong

    2010-05-01

    Although anesthetic agents are known to affect cerebral metabolism, pentobarbital and ketamine have been widely used for animal imaging studies. The purpose of this study is to evaluate alterations in striatum metabolites in dogs between anesthetized with pentobarbital and with ketamine in proton magnetic resonance spectroscopy ((1)H-MRS). (1)H-MRS was performed to ten healthy adult beagle dogs (9-11 kg) at a field strength of 3 T in order to identify metabolic changes after pentobarbital or ketamine administration in the striatum in vivo. Ten dogs were divided into 2 groups as follows: 5 as the pentobarbital-administered group (P group) and 5 as the ketamine-administered group (K group). We found that levels of Glx of the P group was significantly lower than that of the K group (6.90 +/- 0.99 (SD) vs 9.77 +/- 1.14 in 5 dogs, p= 0.003). In addition, the P group also has lower levels of Cr (6.29 +/- 0.44 vs 7.89 +/- 0.91 in 5 dogs, p=0.009) and NAA (5.02 +/- 0.65 vs 6.45 +/- 1.13 in 5 dogs, p=0.041) compared to the K group. However, there were no significant difference between the P group and the K group in striatal levels of Cho and Ins (p>0.1). We demonstrated that MRS-measured metabolites in the specific regions of the brain can be influenced by anesthetic agents.

  4. Different involvement of medial prefrontal cortex and dorso-lateral striatum in automatic and controlled processing of a future conditioned stimulus.

    Science.gov (United States)

    Pérez-Díaz, Francisco; Díaz, Estrella; Sánchez, Natividad; Vargas, Juan Pedro; Pearce, John M; López, Juan Carlos

    2017-01-01

    Recent studies support the idea that stimulus processing in latent inhibition can vary during the course of preexposure. Controlled attentional mechanisms are said to be important in the early stages of preexposure, while in later stages animals adopt automatic processing of the stimulus to be used for conditioning. Given this distinction, it is possible that both types of processing are governed by different neural systems, affecting differentially the retrieval of information about the stimulus. In the present study we tested if a lesion to the dorso-lateral striatum or to the medial prefrontal cortex has a selective effect on exposure to the future conditioned stimulus (CS). With this aim, animals received different amounts of exposure to the future CS. The results showed that a lesion to the medial prefrontal cortex enhanced latent inhibition in animals receiving limited preexposure to the CS, but had no effect in animals receiving extended preexposure to the CS. The lesion of the dorso-lateral striatum produced a decrease in latent inhibition, but only in animals with an extended exposure to the future conditioned stimulus. These results suggest that the dorsal striatum and medial prefrontal cortex play essential roles in controlled and automatic processes. Automatic attentional processes appear to be impaired by a lesion to the dorso-lateral striatum and facilitated by a lesion to the prefrontal cortex.

  5. The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

    Science.gov (United States)

    Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

    2016-01-01

    Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…

  6. In vivo study on the monoamine neurotransmitters and their metabolites change in the striatum of Parkinsonian rats by liquid chromatography with an acetylene black nanoparticles modified electrode.

    Science.gov (United States)

    Lin, Li; Yang, Jie; Lin, Ruipo; Yu, Li; Gao, Hongchang; Yang, Shulin; Li, Xiaokun

    2013-01-01

    The variation in the concentration of monoamine neurotransmitters and their metabolites in an experimental Parkinsonian animal model established by unilateral 6-hydroxydopamine administration was studied. For the purpose of detecting monoamine neurotransmitters and their metabolites more sensitively, an acetylene black nanoparticles modified electrode was fabricated and used as the working electrode for an electrochemical detector in HPLC. The results indicated that the modified electrode exhibited efficiently electrocatalytic oxidation for monoamine neurotransmitters and their metabolites with relatively high sensitivity, long life, and stability. The linear ranges spanned four orders of magnitude (r>0.998) and the detectability was on the level of 0.1 nmolL(-1). The percent relative standard deviation (%RSD) for each compound at all concentration levels was lower than 2.57% and 1.94% for intra-day and inter-day precision, respectively. The mean recovery values were between 98.75% and 105.25%, and the %RSD was found to be less than 1.02%. Coupled with in vivo microdialysis sampling, the validated method was successfully applied to measure monoamine neurotransmitters and their metabolites in both sides of the striatum of conscious and freely moving Parkinsonian rats, and the extracellular monoamine neurotransmitters and their metabolites in the lesioned-side striatum of unilateral 6-hydroxydopamine-lesioned rats were lower than that in the intact side striatum or in the striatum of control rats. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. EFFECT OF PRECURSOR LOADING ON THE SYNTHESIS RATE AND RELEASE OF DOPAMINE AND SEROTONIN IN THE STRIATUM - A MICRODIALYSIS STUDY IN CONSCIOUS RATS

    NARCIS (Netherlands)

    WESTERINK, BHC; DEVRIES, JB

    The effects of systemic administration of tyrosine and phenylalanine on the extracellular levels of tyrosine and dopamine were determined by microdialysis in the striatum of awake rats. In addition, the effects of these precursors on in vivo 3,4-dihydroxyphenylalanine (DOPA) formation were

  8. Changes in expression of delta FosB and the Fos family proteins following NMDA receptor activation in the rat striatum.

    Science.gov (United States)

    Hollen, K M; Nakabeppu, Y; Davies, S W

    1997-07-01

    Receptor-induced expression of transcription factors of the activator protein-1 (AP-1) family in neurons occurs in a unique temporal pattern which regulates subsequent downstream gene expression. We investigated the expression of the Fos family proteins following injection of the NMDA receptor agonist quinolinic acid (QA) into the rat striatum. The c-Fos protein is rapidly and transiently expressed, followed by the sequential and overlapping expression in the same striatal neurons of FosB, from 4 to 8 h post-lesion and delta FosB from 6 h to beyond 30 h post-lesion. Analysis confirms that mRNA transcripts of both fosB and alternatively spliced delta fosB are expressed in the striatum after QA lesion. The Fos-related antigens Fra-1 and Fra-2 and three previously uncharacterized c-Fos-related proteins were additionally found in the striatum which do not increase following lesion. These proteins are related to the highly conserved DNA-binding domain of c-Fos but are not immunologically related to the FosB protein as has been previously reported for proteins induced following chronic stimulation of the striatum. We additionally demonstrate that the c-Fos and delta FosB proteins expressed following QA lesion bind to the functional AP-1 site in the promoter of the nerve growth factor (NGF) gene, the regulation of which temporally and spatially coincides with the AP-1 protein increases in the QA-lesioned striatum. However, the levels of binding to the NGF AP-1 site do not increase throughout time following lesion despite the induced expression of Fos family proteins, suggesting that the regulation of the NGF gene in this paradigm does not simply involve increased binding to the AP-1 site in the NGF gene promoter.

  9. Reverse microdialysis of a 5-HT2A receptor antagonist alters extracellular glutamate levels in the striatum of the MPTP mouse model of Parkinson's disease.

    Science.gov (United States)

    Ferguson, Marcus C; Nayyar, Tultul; Ansah, Twum A

    2014-05-01

    Clinical observations have suggested that antagonism of 5-HT2A receptors may benefit patients with parkinsonian symptomatology. The mechanism of the antiparkinsonian effects of 5-HT2A receptor antagonists has not been fully elucidated. We have shown that the selective 5-HT2A receptor antagonist M100907 [R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenethyl)]-4-piperidinemethanol] improved motor impairments in mice treated with the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In Parkinson's disease (PD) patients and animal models of parkinsonism dopamine denervation is associated with increased cortico-striatal glutamatergic transmission. We hypothesized that 5-HT2A receptor antagonists may exert their antiparkinsonian effects by decreasing striatal glutamate. Here, using in vivo microdialysis, we have shown an increased basal level of extracellular striatal glutamate when measured 3weeks after MPTP administration. The local administration of M100907 to the striatum significantly decreased striatal extracellular glutamate levels in MPTP-treated and saline treated mice. Basal extracellular serotonin (5-HT) levels were also elevated, whereas dopamine (DA) levels were significantly reduced in the striatum of MPTP-treated mice. Infusion of M100907 into the striatum produced no effect on dopamine or 5-HT levels. Local application of tetrodotoxin suppressed glutamate, 5-HT and DA concentrations in striatal dialysates in the presence or absence of M100907. The striatal expression of the glutamate transporter GLT1 was unchanged. However, there was an upregulation of the expression of 5-HT2A receptors in the striatum of MPTP-treated animals. Our data provide further evidence of enhanced glutamatergic neurotransmission in parkinsonism and demonstrate that blocking 5-HT2A receptors in the striatum will normalize glutamatergic neurotransmission. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Sub-chronic exposure to the insecticide dimethoate induces a proinflammatory status and enhances the neuroinflammatory response to bacterial lypopolysaccharide in the hippocampus and striatum of male mice

    Energy Technology Data Exchange (ETDEWEB)

    Astiz, Mariana, E-mail: marianaastiz@gmail.com; Diz-Chaves, Yolanda, E-mail: ydiz@cajal.csic.es; Garcia-Segura, Luis M., E-mail: lmgs@cajal.csic.es

    2013-10-15

    Dimethoate is an organophosphorus insecticide extensively used in horticulture. Previous studies have shown that the administration of dimethoate to male rats, at a very low dose and during a sub-chronic period, increases the oxidation of lipids and proteins, reduces the levels of antioxidants and impairs mitochondrial function in various brain regions. In this study, we have assessed in C57Bl/6 adult male mice, whether sub-chronic (5 weeks) intoxication with a low dose of dimethoate (1.4 mg/kg) affects the expression of inflammatory molecules and the reactivity of microglia in the hippocampus and striatum under basal conditions and after an immune challenge caused by the systemic administration of lipopolysaccharide. Dimethoate increased mRNA levels of tumor necrosis factor α (TNFα) and interleukin (IL) 6 in the hippocampus, and increased the proportion of Iba1 immunoreactive cells with reactive phenotype in dentate gyrus and striatum. Lipopolysaccharide caused a significant increase in the mRNA levels of IL1β, TNFα, IL6 and interferon-γ-inducible protein 10, and a significant increase in the proportion of microglia with reactive phenotype in the hippocampus and the striatum. Some of the effects of lipopolysaccharide (proportion of Iba1 immunoreactive cells with reactive phenotype and IL6 mRNA levels) were amplified in the animals treated with dimethoate, but only in the striatum. These findings indicate that a sub-chronic period of administration of a low dose of dimethoate, comparable to the levels of the pesticide present as residues in food, causes a proinflammatory status in the brain and enhances the neuroinflammatory response to the lipopolysaccharide challenge with regional specificity. - Highlights: • The dose of pesticide used was comparable to the levels of residues found in food. • Dimethoate administration increased cytokine expression and microglia reactivity. • Hippocampus and striatum were differentially affected by the treatment.

  11. Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model.

    Science.gov (United States)

    Lazzarini, Marcio; Martin, Sabine; Mitkovski, Mišo; Vozari, Rita Raisman; Stühmer, Walter; Bel, Elaine Del

    2013-07-01

    Neuron-glia interactions play a key role in maintaining and regulating the central nervous system. Glial cells are implicated in the function of dopamine neurons and regulate their survival and resistance to injury. Parkinson's disease is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, decreased striatal dopamine levels and consequent onset of extrapyramidal motor dysfunction. Parkinson's disease is a common chronic, neurodegenerative disorder with no effective protective treatment. In the 6-OHDA mouse model of Parkinson's disease, doxycycline administered at a dose that both induces/represses conditional transgene expression in the tetracycline system, mitigates the loss of dopaminergic neurons in the substantia nigra compacta and nerve terminals in the striatum. This protective effect was associated with: (1) a reduction of microglia in normal mice as a result of doxycycline administration per se; (2) a decrease in the astrocyte and microglia response to the neurotoxin 6-OHDA in the globus pallidus and substantia nigra compacta, and (3) the astrocyte reaction in the striatum. Our results suggest that doxycycline blocks 6-OHDA neurotoxicity in vivo by inhibiting microglial and astrocyte expression. This action of doxycycline in nigrostriatal dopaminergic neuron protection is consistent with a role of glial cells in Parkinson's disease neurodegeneration. The neuroprotective effect of doxycycline may be useful in preventing or slowing the progression of Parkinson's disease and other neurodegenerative diseases linked to glia function. Copyright © 2013 Wiley Periodicals, Inc.

  12. Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders.

    Science.gov (United States)

    Pierucci, Massimo; Galati, Salvatore; Valentino, Mario; Di Matteo, Vincenzo; Benigno, Arcangelo; Pitruzzella, Alessandro; Muscat, Richard; Di Giovanni, Giuseppe

    2011-11-01

    Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this paper, the distribution of NO in the BG nuclei will be described. Furthermore, evidence demonstrating the nitrergic control of BG activity will be reviewed. The new avenues that the increasing knowledge of NO in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. For example, inhibition of striatal NO/guanosine monophosphate signal pathway by phosphodiesterases seems to be effective in levodopa-induced dyskinesia. However, the results of experimental studies have to be interpreted with caution given the complexities of nitrergic signalling and the limitations of animal models. Nevertheless, the NO system represents a promising pharmacological intervention for treating Parkinson's disease and related disorders.

  13. Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI.

    Science.gov (United States)

    Van Den Berge, Nathalie; Albaugh, Daniel L; Salzwedel, Andrew; Vanhove, Christian; Van Holen, Roel; Gao, Wei; Stuber, Garret D; Ian Shih, Yen-Yu

    2017-02-01

    The substantia nigra pars reticulata (SNr) and external globus pallidus (GPe) constitute the two major output targets of the rodent striatum. Both the SNr and GPe converge upon thalamic relay nuclei (directly or indirectly, respectively), and are traditionally modeled as functionally antagonistic relay inputs. However, recent anatomical and functional studies have identified unanticipated circuit connectivity in both the SNr and GPe, demonstrating their potential as far more than relay nuclei. In the present study, we employed simultaneous deep brain stimulation and functional magnetic resonance imaging (DBS-fMRI) with cerebral blood volume (CBV) measurements to functionally and unbiasedly map the circuit- and network level connectivity of the SNr and GPe. Sprague-Dawley rats were implanted with a custom-made MR-compatible stimulating electrode in the right SNr (n=6) or GPe (n=7). SNr- and GPe-DBS, conducted across a wide range of stimulation frequencies, revealed a number of surprising evoked responses, including unexpected CBV decreases within the striatum during DBS at either target, as well as GPe-DBS-evoked positive modulation of frontal cortex. Functional connectivity MRI revealed global modulation of neural networks during DBS at either target, sensitive to stimulation frequency and readily reversed following cessation of stimulation. This work thus contributes to a growing literature demonstrating extensive and unanticipated functional connectivity among basal ganglia nuclei. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.

    Science.gov (United States)

    Kim, Hannah; Kim, Tae-Kyung; Kim, Ji-Eun; Park, Jin-Young; Lee, Yunjin; Kang, Minkyung; Kim, Kyoung-Shim; Han, Pyung-Lim

    2014-11-07

    Behavioral choices in habits and innate behaviors occur automatically in the absence of conscious selection. These behaviors are not easily modified by learning. Similar types of behaviors also occur in various mental illnesses including drug addiction, obsessive-compulsive disorder, schizophrenia, and autism. However, underlying mechanisms are not clearly understood. In the present study, we investigated the molecular mechanisms regulating unconditioned preferred behaviors in food-choices. Mice lacking adenylyl cyclase-5 (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed food pellets nearly one after another in cages. AC5 KO mice showed aversive behaviors to bitter tasting quinine, but they compulsively chose quinine-containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors in AC5 KO mice were due to the gain of behavioral preferences for food pellets containing an olfactory cue, which wild-type mice normally ignored. Such food-choice behaviors in AC5 KO mice disappeared when whiskers were trimmed. Conversely, whisker trimming in wildtype mice induced behavioral preferences for AC5 KO food pellets, indicating that preferred food-choices were not learned through prior experience. Both AC5 KO mice and wildtype mice with trimmed whiskers had increased glutamatergic input from the barrel cortex into the dorsal striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food pellets, thus mimicking AC5 KO phenotypes. Our results show that the gain and loss of behavioral preferences for a specific cue-directed option were regulated by specific cellular factors in the dorsal striatum, such

  15. Prior Cocaine Self-Administration Increases Response-Outcome Encoding That Is Divorced from Actions Selected in Dorsal Lateral Striatum.

    Science.gov (United States)

    Burton, Amanda C; Bissonette, Gregory B; Zhao, Adam C; Patel, Pooja K; Roesch, Matthew R

    2017-08-09

    Dorsal lateral striatum (DLS) is a highly associative structure that encodes relationships among environmental stimuli, behavioral responses, and predicted outcomes. DLS is known to be disrupted after chronic drug abuse; however, it remains unclear what neural signals in DLS are altered. Current theory suggests that drug use enhances stimulus-response processing at the expense of response-outcome encoding, but this has mostly been tested in simple behavioral tasks. Here, we investigated what neural correlates in DLS are affected by previous cocaine exposure as rats performed a complex reward-guided decision-making task in which predicted reward value was independently manipulated by changing the delay to or size of reward associated with a response direction across a series of trial blocks. After cocaine self-administration, rats exhibited stronger biases toward higher-value reward and firing in DLS more strongly represented action-outcome contingencies independent from actions subsequently taken rather than outcomes predicted by selected actions (chosen-outcome contingencies) and associations between stimuli and actions (stimulus-response contingencies). These results suggest that cocaine self-administration strengthens action-outcome encoding in rats (as opposed to chosen-outcome or stimulus-response encoding), which abnormally biases behavior toward valued reward when there is a choice between two options during reward-guided decision-making. SIGNIFICANCE STATEMENT Current theories suggest that the impaired decision-making observed in individuals who chronically abuse drugs reflects a decrease in goal-directed behaviors and an increase in habitual behaviors governed by neural representations of response-outcome (R-O) and stimulus-response associations, respectively. We examined the impact that prior cocaine self-administration had on firing in dorsal lateral striatum (DLS), a brain area known to be involved in habit formation and affected by drugs of abuse

  16. Tauopathic changes in the striatum of A53T α-synuclein mutant mouse model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Jonathan Wills

    2011-03-01

    Full Text Available Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of

  17. Reward-Related Ventral Striatum Activity Buffers against the Experience of Depressive Symptoms Associated with Sleep Disturbances.

    Science.gov (United States)

    Avinun, Reut; Nevo, Adam; Knodt, Annchen R; Elliott, Maxwell L; Radtke, Spenser R; Brigidi, Bartholomew D; Hariri, Ahmad R

    2017-10-04

    Sleep disturbances represent one risk factor for depression. Reward-related brain function, particularly the activity of the ventral striatum (VS), has been identified as a potential buffer against stress-related depression. We were therefore interested in testing whether reward-related VS activity would moderate the effect of sleep disturbances on depression in a large cohort of young adults. Data were available from 1129 university students (mean age 19.71 ± 1.25 years; 637 women) who completed a reward-related functional MRI task to assay VS activity and provided self-reports of sleep using the Pittsburgh Sleep Quality Index and symptoms of depression using a summation of the General Distress/Depression and Anhedonic Depression subscales of the Mood and Anxiety Symptoms Questionnaire-short form. Analyses revealed that as VS activity increased the association between sleep disturbances and depressive symptoms decreased. The interaction between sleep disturbances and VS activity was robust to the inclusion of sex, age, race/ethnicity, past or present clinical disorder, early and recent life stress, and anxiety symptoms, as well as the interactions between VS activity and early or recent life stress as covariates. We provide initial evidence that high reward-related VS activity may buffer against depressive symptoms associated with poor sleep. Our analyses help advance an emerging literature supporting the importance of individual differences in reward-related brain function as a potential biomarker of relative risk for depression. SIGNIFICANCE STATEMENT Sleep disturbances are a common risk factor for depression. An emerging literature suggests that reward-related activity of the ventral striatum (VS), a brain region critical for motivation and goal-directed behavior, may buffer against the effect of negative experiences on the development of depression. Using data from a large sample of 1129 university students we demonstrate that as reward-related VS activity

  18. Chronic low dose Adderall XR down-regulates cfos expression in infantile and prepubertal rat striatum and cortex.

    Science.gov (United States)

    Allen, J K; Wilkinson, M; Soo, E C; Hui, J P M; Chase, T D; Carrey, N

    2010-09-15

    We previously reported that treatment of prepubertal male rats with low, injected or oral, doses of methylphenidate stimulated cfos, fosB and arc expression in many areas of the developing brain. In the present study our objective was to determine whether the widely prescribed psychostimulant Adderall XR (ADD) exerted similar effects in infantile and prepubertal rat brain. We report here, for the first time, that low threshold doses of oral ADD, an extended-release mixture of amphetamine salts, now routinely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), also increased cfos expression in infantile (postnatal day 10; PD10) and prepubertal (PD24) rat brain. These threshold doses were correlated with blood levels of amphetamine determined by liquid chromatography-mass spectrometry. Moreover, we observed that chronic treatment with oral ADD (1.6 mg/kg; x 14 days) not only significantly down-regulated cfos expression following a final challenge dose of ADD in prepubertal (PD24) rat striatum and cortex, quantified in terms of FOS immunoreactivity (FOS-ir), but did so at a daily dose that was without effect with methylphenidate (MPH); that is a much higher oral dose of MPH (7.5 mg/kg; x 14 days) failed to induce down-regulation of cfos expression. Similar experiments in infantile rats (PD10), but using a threshold injected dose of ADD (1.25 mg/kg sc) also significantly reduced striatal and cingulate cortical FOS-ir. An additional finding in the prepubertal rats was that oral ADD-induced FOS-ir was observed in the cerebral cortex following doses lower than the threshold dose necessary to increase FOS-ir in the striatum. This was not the case in the PD10 rats. In conclusion, our efforts to calibrate biological responses, such as immediate early gene expression, to clinically relevant blood levels of stimulants confirmed that expression of cfos is very sensitive to repeated low doses of Adderall XR. It is now feasible to examine whether other

  19. Instructed knowledge shapes feedback-driven aversive learning in striatum and orbitofrontal cortex, but not the amygdala

    Science.gov (United States)

    Atlas, Lauren Y; Doll, Bradley B; Li, Jian; Daw, Nathaniel D; Phelps, Elizabeth A

    2016-01-01

    Socially-conveyed rules and instructions strongly shape expectations and emotions. Yet most neuroscientific studies of learning consider reinforcement history alone, irrespective of knowledge acquired through other means. We examined fear conditioning and reversal in humans to test whether instructed knowledge modulates the neural mechanisms of feedback-driven learning. One group was informed about contingencies and reversals. A second group learned only from reinforcement. We combined quantitative models with functional magnetic resonance imaging and found that instructions induced dissociations in the neural systems of aversive learning. Responses in striatum and orbitofrontal cortex updated with instructions and correlated with prefrontal responses to instructions. Amygdala responses were influenced by reinforcement similarly in both groups and did not update with instructions. Results extend work on instructed reward learning and reveal novel dissociations that have not been observed with punishments or rewards. Findings support theories of specialized threat-detection and may have implications for fear maintenance in anxiety. DOI: http://dx.doi.org/10.7554/eLife.15192.001 PMID:27171199

  20. Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum.

    Directory of Open Access Journals (Sweden)

    Evgeny Bychkov

    Full Text Available G protein-coupled receptor kinases (GRKs and arrestins mediate desensitization of G protein-coupled receptors (GPCR. Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling.

  1. Investigating the dynamics of the brain response to music: A central role of the ventral striatum/nucleus accumbens.

    Science.gov (United States)

    Mueller, Karsten; Fritz, Thomas; Mildner, Toralf; Richter, Maxi; Schulze, Katrin; Lepsien, Jöran; Schroeter, Matthias L; Möller, Harald E

    2015-08-01

    Ventral striatal activity has been previously shown to correspond well to reward value mediated by music. Here, we investigate the dynamic brain response to music and manipulated counterparts using functional magnetic resonance imaging (fMRI). Counterparts of musical excerpts were produced by either manipulating the consonance/dissonance of the musical fragments or playing them backwards (or both). Results show a greater involvement of the ventral striatum/nucleus accumbens both when contrasting listening to music that is perceived as pleasant and listening to a manipulated version perceived as unpleasant (backward dissonant), as well as in a parametric analysis for increasing pleasantness. Notably, both analyses yielded a ventral striatal response that was strongest during an early phase of stimulus presentation. A hippocampal response to the musical stimuli was also observed, and was largely mediated by processing differences between listening to forward and backward music. This hippocampal involvement was again strongest during the early response to the music. Auditory cortex activity was more strongly evoked by the original (pleasant) music compared to its manipulated counterparts, but did not display a similar decline of activation over time as subcortical activity. These findings rather suggest that the ventral striatal/nucleus accumbens response during music listening is strongest in the first seconds and then declines. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Differential Patterns of Amygdala and Ventral Striatum Activation Predict Gender-Specific Changes in Sexual Risk Behavior

    Science.gov (United States)

    Sansosti, Alexandra A.; Bowman, Hilary C.; Hariri, Ahmad R.

    2015-01-01

    Although the initiation of sexual behavior is common among adolescents and young adults, some individuals express this behavior in a manner that significantly increases their risk for negative outcomes including sexually transmitted infections. Based on accumulating evidence, we have hypothesized that increased sexual risk behavior reflects, in part, an imbalance between neural circuits mediating approach and avoidance in particular as manifest by relatively increased ventral striatum (VS) activity and relatively decreased amygdala activity. Here, we test our hypothesis using data from seventy 18- to 22-year-old university students participating in the Duke Neurogenetics Study. We found a significant three-way interaction between amygdala activation, VS activation, and gender predicting changes in the number of sexual partners over time. Although relatively increased VS activation predicted greater increases in sexual partners for both men and women, the effect in men was contingent on the presence of relatively decreased amygdala activation and the effect in women was contingent on the presence of relatively increased amygdala activation. These findings suggest unique gender differences in how complex interactions between neural circuit function contributing to approach and avoidance may be expressed as sexual risk behavior in young adults. As such, our findings have the potential to inform the development of novel, gender-specific strategies that may be more effective at curtailing sexual risk behavior. PMID:26063921

  3. Local application of SCH 39166 reversibly and dose-dependently decreases acetylcholine release in the rat striatum.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-11-03

    The effect of local application by reverse dialysis of the dopamine D(1) receptor antagonist (-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride (SCH 39166) on acetylcholine release was studied in awake, freely moving rats implanted with concentric microdialysis probes in the dorsal striatum. In these experiments, the reversible acetylcholine esterase inhibitor, neostigmine, was added to the perfusion solution at two different concentrations, 0.01 and 0.1 microM. SCH 39166 (1, 5 and 10 microM), in the presence of 0.01 microM neostigmine, reversibly decreased striatal acetylcholine release (1 microM SCH 39166 by 8+/-4%; 5 microM SCH 39166 by 24+/-5%; 10 microM SCH 39166 by 27+/-7%, from basal). Similarly, SCH 39166, applied in the presence of a higher neostigmine concentration (0.1 microM), decreased striatal acetylcholine release by 14+/-4% at 1 microM, by 28+/-8% at 5 microM and by 30+/-5% at 10 microM, in a dose-dependent and time-dependent manner. These results are consistent with the existence of a facilitatory tone of dopamine on striatal acetylcholine transmission mediated by dopamine D(1) receptors located on striatal cholinergic interneurons.

  4. The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance.

    Science.gov (United States)

    Innocenti, Giorgio M; Dyrby, Tim B; Andersen, Kasper Winther; Rouiller, Eric M; Caminiti, Roberto

    2017-06-01

    The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4-0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon diameters and conduction distance are <2 ms in the monkey and, by extrapolation, <4 ms in humans. This delay corresponds to the performance in Poffenberger's paradigm, a classical attempt to estimate central conduction delays, with a neuropsychological task. In both species, callosal cortico-striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported to dissociate syntax and prosody. The projection might originate from an overproduction of callosal projections in development, differentially pruned depending on species. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine-somatostatin interactions in the striatum

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Iverson, M.T.; Radke, J.M.; Vincent, S.R.

    1986-06-01

    The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin.

  6. Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

    Directory of Open Access Journals (Sweden)

    Yin Shou

    2013-01-01

    Full Text Available Electroacupuncture (EA has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36 and Kunlun (BL60 acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001. The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression.

  7. The effect of crack cocaine addiction on the microstructure and morphology of the human striatum and thalamus using novel shape analysis and fast diffusion kurtosis imaging

    DEFF Research Database (Denmark)

    Garza-Villarreal, Eduardo A.; Mallar, Chakravarty; Hansen, Brian

    2016-01-01

    The striatum and thalamus are subcortical structures intimately involved in addiction, and the morphology and microstructure of these has been studied in murine models of cocaine addiction. However, human studies using non-invasive MRI has shown inconsistencies in morphology using volumetric...... analysis. In our study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack cocaine addiction (CA) compared to matched healthy controls (HC). We did not find....... Our findings suggest that the use of finer methods and sequences is needed to characterize morphological and microstructural changes in cocaine addiction, and that brain changes in cocaine addiction are related to age....

  8. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Stott, Simon R W; Mattsson, Bengt

    2010-01-01

    Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic....... Our results show that striatal delivery of rAAV5 vectors in the neonatal brain represents a useful tool to express genes of interest both in the basal ganglia and the neocortex. Furthermore, we apply, for the first time, viral vector-mediated gene transfer to the pig brain providing the opportunity...... delivery to the neonatal rat and minipig striatum. The efficiency of GFP expression and the phenotype of GFP-positive cells were assessed within the forebrain at different time points up to 12 months after surgery. Both rAAV1-GFP and rAAV5-GFP delivery resulted in transduction of the striatum as well...

  9. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism....

  10. Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver.

    Directory of Open Access Journals (Sweden)

    Jong-Min Lee

    Full Text Available Age at onset of Huntington's disease (HD is largely determined by the CAG trinucleotide repeat length in the HTT gene. Importantly, the CAG repeat undergoes tissue-specific somatic instability, prevalent in brain regions that are disease targets, suggesting a potential role for somatic CAG repeat instability in modifying HD pathogenesis. Thus, understanding underlying mechanisms of somatic CAG repeat instability may lead to discoveries of novel therapeutics for HD. Investigation of the dynamics of the CAG repeat size changes over time may provide insights into the mechanisms underlying CAG repeat instability.To understand how the HTT CAG repeat length changes over time, we quantified somatic instability of the CAG repeat in Huntington's disease CAG knock-in mice from 2-16 months of age in liver, striatum, spleen and tail. The HTT CAG repeat in spleen and tail was very stable, but that in liver and striatum expanded over time at an average rate of one CAG per month. Interestingly, the patterns of repeat instability were different between liver and striatum. Unstable CAG repeats in liver repeatedly gained similar sizes of additional CAG repeats (approximately two CAGs per month, maintaining a distinct population of unstable repeats. In contrast, unstable CAG repeats in striatum gained additional repeats with different sizes resulting in broadly distributed unstable CAG repeats. Expanded CAG repeats in the liver were highly enriched in polyploid hepatocytes, suggesting that the pattern of liver instability may reflect the restriction of the unstable repeats to a unique cell type.Our results are consistent with repeat expansion occurring as a consequence of recurrent small repeat insertions that differ in different tissues. Investigation of the specific mechanisms that underlie liver and striatal instability will contribute to our understanding of the relationship between instability and disease and the means to intervene in this process.

  11. Effect of Paullinia cupana Mart. Commercial Extract During the Aging of Middle Age Wistar Rats: Differential Effects on the Hippocampus and Striatum.

    Science.gov (United States)

    Mingori, Moara Rodrigues; Heimfarth, Luana; Ferreira, Charles Francisco; Gomes, Henrique Mautone; Moresco, Karla Suzana; Delgado, Jeferson; Roncato, Sabrina; Zeidán-Chuliá, Fares; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2017-08-01

    During aging, there is a marked decline in the antioxidant capacity of brain tissue, leading to a gradual loss of the antioxidant/oxidant balance, which causes oxidative damage. The effects of Paullinia cupana Mart. extract, which is described as being rich in caffeine and many polyphenol compounds, on the central nervous system have not been extensively investigated. The aim of this study was to therefore investigate the effect of a commercial guarana extract (CGE) on cognitive function, oxidative stress, and brain homeostasis proteins related to cognitive injury and senescence in middle age, male Wistar rats. Animals were randomly assigned to a group according to their treatment (saline, CGE, or caffeine). Solutions were administered daily by oral gavage for 6 months. Open field and novel object recognition tasks were performed before and after treatment. Biochemical analyses were carried out on the hippocampus and striatum. Our open field data showed an increase in exploratory activity and a decrease in anxiety-like behavior with caffeine but not with the CGE treatment. In the CGE-treated group, catalase activity decreased in the hippocampus and increased in the striatum. Analyses of the hippocampus and striatum indicate that CGE and/or caffeine altered some of the analyzed parameters in a tissue-specific manner. Our data suggest that CGE intake does not improve cognitive development, but modifies the oxidative stress machinery and neurodegenerative-signaling pathway, inhibiting pro-survival pathway molecules in the hippocampus and striatum. This may contribute to the development of unfavorable microenvironments in the brain and neurodegenerative disorders.

  12. Cognitive performance correlates with the degree of dopaminergic degeneration in the associative part of the striatum in non-demented Parkinson's patients.

    Science.gov (United States)

    Kübler, Dorothee; Schroll, Henning; Buchert, Ralph; Kühn, Andrea A

    2017-09-01

    Parkinson's disease (PD) patients show cognitive deficits that are relevant in terms of prognosis and quality of life. Degeneration of striatal dopaminergic afferents proceeds from dorsal/caudal to anterior/ventral and is discussed to account for some of these symptoms. Treatment with dopamine (DA) has differential effects on cognitive dysfunctions, improving some and worsening others. We hypothesized that cognitive performance during the dopaminergic OFF state correlates with DAT availability in the associative striatum. 16 PD patients underwent motor and cognitive examination ON and OFF DA. Global cognition was measured using the Montréal Cognitive Assessment (MoCA) test and executive functioning using a Stroop test. Nigrostriatal dopaminergic innervation was characterized with [ 123 I]FP-CIT SPECT. A connectivity atlas of the striatum was used to assess DAT availability in functionally defined striatal subregions. Correlations between imaging data and behavioral data OFF medication were calculated. Correlations between DAT availability and MoCA performance in the dopaminergic OFF state was strongest in the associative part of the striatum (r = 0.674, p = 0.004). MoCA test performance did not differ between the ON and the OFF state. There was no correlation of DAT availability with Stroop performance in the OFF state but performance was significantly better during the ON state. Not only motor but also cognitive dysfunctions in PD are associated with striatal dopaminergic depletion. Cognitive decline in non-demented PD patients goes along with nigrostriatal degeneration, most pronounced in the associative subdivision of the striatum. In addition, the present findings suggest that executive dysfunctions are ameliorated by DA whereas global cognition is not improved by dopaminergic medication.

  13. Sequential Adeno-Associated Viral Vector Serotype 9-Green Fluorescent Protein Gene Transfer Causes Massive Inflammation and Intense Immune Response in Rat Striatum.

    Science.gov (United States)

    Yang, Chun; Hao, Fei; He, Jun; Lu, Tao; Klein, Ronald L; Zhao, Li-Ru; Duan, Wei-Ming

    2016-07-01

    Green fluorescent protein (GFP) is a broadly used live cell reporter for gene transduction although side effects associated with GFP in gene transfer are reported. The present study was designed to systematically examine host responses, including inflammatory and immune responses, induced by persistent overexpression of the GFP gene mediated by adeno-associated viral vector serotype 9 (AAV9), and their effects on GFP gene transduction in rat striatum. Our results show that host responses against AAV9-GFP transduction, and GFP transgene expression in the striatum exhibited a temporal and dose-dependent pattern. Both muscular and striatal delivery of AAV9-GFP increased levels of inflammation and immune reactions against sequential AAV9-GFP transduction in the striatum, leading to reduced levels of GFP expression. We also observed that rat sera from sequential administrations of AAV9-GFP group had significantly higher levels of neutralizing antibody against AAV9 vectors when compared with the age-matched rats. As excessive GFP can trigger vigorous inflammation and intense immune response after GFP gene transduction, the use of GFP as a live cell marker protein should be deliberated, especially in repeated administration studies.

  14. Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age

    Directory of Open Access Journals (Sweden)

    James N. Porter

    2015-02-01

    Full Text Available The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC imaging in 106 healthy individuals, ages 9–44. Broadly, the dorsal striatum (DS is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns and dorsal anterior cingulate cortex (dACC that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents’ unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

  15. Bidirectional Control of Reversal in a Dual Action Task by Direct and Indirect Pathway Activation in the Dorsolateral Striatum in Mice

    Directory of Open Access Journals (Sweden)

    Muriel Laurent

    2017-12-01

    Full Text Available The striatum is a key brain structure involved in the processing of cognitive flexibility, which results from the balance between the flexibility demanded for novel learning of motor actions and the inflexibility required to preserve previously learned actions. In particular, the dorsolateral portion of the striatum (DLS is engaged in the learning of action sequence. This process is temporally driven by fine adjustments in the function of the two main neuronal populations of the striatum, known as the direct pathway medium spiny neurons (dMSNs and indirect pathway medium spiny neurons (iMSNs. Here, using optogenetics, behavioral, and electrophysiological tools, we addressed the relative role of both neuronal populations in the acquisition of a reversal dual action sequence in the DLS. While the channelrhodopsin-induced activation of dMSNs and iMSNs of the DLS did not induce changes in the learning rate of the sequence, the specific activation of the dMSNs of the DLS facilitated the acquisition of a reversal dual action sequence; the activation of iMSNs induced a significant deficit in the acquisition of the same task. Taken together our results indicate an antagonistic relationship between dMSNs and iMSNs on the acquisition of a reversal dual action sequence.

  16. Low and high gamma oscillations in rat ventral striatum have distinct relationships to behavior, reward, and spiking activity on a learned spatial decision task

    Directory of Open Access Journals (Sweden)

    Matthijs A A Van Der Meer

    2009-06-01

    Full Text Available Local field potential (LFP oscillations in the brain reflect organization thought to be important for perception, attention, movement, and memory. In the basal ganglia, including dorsal striatum, dysfunctional LFP states are associated with Parkinson’s disease, while in healthy subjects, dorsal striatal LFPs have been linked to decision-making processes. However, LFPs in ventral striatum have been less studied. We report that in rats running a spatial decision task, prominent gamma-50 (45-55 Hz and gamma-80 (70-85 Hz oscillations in ventral striatum had distinct relationships to behavior, task events, and spiking activity. Gamma-50 power increased sharply following reward delivery and before movement initiation, while in contrast, gamma-80 power ramped up gradually to reward locations. Gamma-50 power was low and contained little structure during early learning, but rapidly developed a stable pattern, while gamma-80 power was initially high before returning to a stable level within a similar timeframe. Putative fast-spiking interneurons (FSIs showed phase, firing rate, and coherence relationships with gamma-50 and gamma-80, indicating that the observed LFP patterns are locally relevant. Furthermore, in a number of FSIs such relationships were specific to gamma-50 or gamma-80, suggesting that partially distinct FSI populations mediate the effects of gamma-50 and gamma-80.

  17. Protein kinase G regulates β-synuclein in response to repeated exposure to cocaine in the rat dorsal striatum in a Ca²⁺-dependent manner.

    Science.gov (United States)

    Yang, Ju Hwan; Choe, Eun Sang

    2014-10-17

    Protein kinase G (PKG) activation plays a crucial role in neuronal plasticity after repeated exposure to cocaine in the dorsal striatum. The present study investigated the characteristics of β-synuclein expression by PKG activation after repeated cocaine administration in the rat dorsal striatum. The results demonstrated that repeated, but not acute, exposure to cocaine (20mg/kg) once a day for 7 consecutive days significantly upregulated expression of β-synuclein. Furthermore, this upregulation was decreased by the depletion of Ca(2+), but not blockade of Na(+) influx. Blockade of N-methyl-d-aspartate (NMDA) receptors and ryanodine-sensitive Ca(2+) channels also decreased the elevation of β-synuclein expression by repeated cocaine administration. Inhibition of neuronal nitric oxide synthase, which can activate PKG, did not alter the expression of β-synuclein elevated by repeated cocaine administration. These findings suggest that the expression of β-synuclein can be regulated by Ca(2+)-dependent PKG activation via stimulation of NMDA receptors and voltage-operated Ca(2+) channels in the endoplasmic reticulum in the dorsal striatum. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Mazindol attenuates the 3,4-methylenedioxymethamphetamine-induced formation of hydroxyl radicals and long-term depletion of serotonin in the striatum.

    Science.gov (United States)

    Shankaran, M; Yamamoto, B K; Gudelsky, G A

    1999-06-01

    The formation of hydroxyl radicals following the systemic administration of 3,4-methylenedioxymethamphetamine (MDMA) was studied in the striatum of the rat by quantifying the stable adducts of salicylic acid and D-phenylalanine, namely, 2,3-dihydroxybenzoic acid (2,3-DHBA) and p-tyrosine, respectively. The repeated administration of MDMA produced a sustained increase in the extracellular concentration of 2,3-DHBA and p-tyrosine, as well as dopamine. The MDMA-induced increase in the extracellular concentration of both dopamine and 2,3-DHBA was suppressed in rats treated with mazindol, a dopamine uptake inhibitor. Mazindol also attenuated the long-term depletion of serotonin (5-HT) in the striatum produced by MDMA without altering the acute hyperthermic response to MDMA. These results are supportive of the view that MDMA produces a dopamine-dependent increase in the formation of hydroxyl radicals in the striatum that may contribute to the mechanism whereby MDMA produces a long-term depletion of brain 5-HT content.

  19. Functional centrality of amygdala, striatum and hypothalamus in a "small-world" network underlying joy: an fMRI study with music.

    Science.gov (United States)

    Koelsch, Stefan; Skouras, Stavros

    2014-07-01

    Current knowledge about small-world networks underlying emotions is sparse, and confined to functional magnetic resonance imaging (fMRI) studies using resting-state paradigms. This fMRI study applied Eigenvector Centrality Mapping (ECM) and functional connectivity analysis to reveal neural small-world networks underlying joy and fear. Joy and fear were evoked using music, presented in 4-min blocks. Results show that the superficial amygdala (SF), laterobasal amygdala (LB), striatum, and hypothalamus function as computational hubs during joy. Out of these computational hubs, the amygdala nuclei showed the highest centrality values. The SF showed functional connectivity during joy with the mediodorsal thalamus (MD) and nucleus accumbens (Nac), suggesting that SF, MD, and Nac modulate approach behavior in response to positive social signals such as joyful music. The striatum was functionally connected during joy with the LB, as well as with premotor cortex, areas 1 and 7a, hippocampus, insula and cingulate cortex, showing that sensorimotor, attentional, and emotional processes converge in the striatum during music perception. The hypothalamus showed functional connectivity during joy with hippocampus and MD, suggesting that hypothalamic endocrine activity is modulated by hippocampal and thalamic activity during sustained periods of music-evoked emotion. Our study indicates high centrality of the amygdala nuclei groups within a functional network underlying joy, suggesting that these nuclei play a central role for the modulation of emotion-specific activity within this network.

  20. Effects of motion correction for dynamic [11C]Raclopride brain PET data on the evaluation of endogenous dopamine release in striatum

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Kim, Yu Kyeong; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun; Choe, Yearn Seong; Kang, Eun Joo

    2005-01-01

    Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head motion correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a momentary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task:110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction

  1. Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

    Science.gov (United States)

    Bossong, Matthijs G; Mehta, Mitul A; van Berckel, Bart N M; Howes, Oliver D; Kahn, René S; Stokes, Paul R A

    2015-08-01

    Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

  2. Dopaminergic and cholinergic regulation of Fyn tyrosine kinase phosphorylation in the rat striatum in vivo.

    Science.gov (United States)

    Mao, Li-Min; Wang, John Q

    2015-12-01

    Src and Fyn are two Src family kinase (SFK) members that are expressed in mammalian brains and play important roles in the regulation of a variety of neuronal and synaptic substrates. Here we investigated the responsiveness of these SFKs to changing dopamine receptor signals in dopamine responsive regions of adult rat brains in vivo. Pharmacological activation of dopamine D1 receptors (D1Rs) by a systemic injection of the selective agonist SKF81297 increased phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) in the striatum, indicating activation of SFKs following SKF81297 injection. The dopamine D2 receptor (D2R) agonist quinpirole had no effect. Blockade of D1Rs with an antagonist SCH23390 did not alter striatal Y416 phosphorylation, while the D2R antagonist eticlopride elevated it. Between Src and Fyn, SKF81297 seemed to preferentially facilitate Fyn phosphorylation. Activation of muscarinic acetylcholine M4 receptors (M4Rs) with a positive allosteric modulator VU0152100 suppressed SFK Y416 responses to SKF81297. Additionally, SKF81297 induced a correlated increase in phosphorylation of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits at a Fyn site (Y1472), which was attenuated by VU0152100. SKF81297 also enhanced synaptic recruitments of active Fyn and GluN1/GluN2B-containing NMDA receptors. These data demonstrate that D1Rs regulate Fyn and downstream NMDA receptors in striatal neurons in vivo. Acetylcholine through activating M4Rs inhibits Fyn and NMDA receptors in their sensitivity to D1R signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Enhancement of striatum-dependent memory by conditioned fear is mediated by beta-adrenergic receptors in the basolateral amygdala

    Directory of Open Access Journals (Sweden)

    Travis D. Goode

    2016-06-01

    Full Text Available Emotional arousal can have a profound impact on various learning and memory processes. For example, unconditioned emotional stimuli (e.g., predator odor or anxiogenic drugs enhance dorsolateral striatum (DLS-dependent habit memory. These effects critically depend on a modulatory role of the basolateral complex of the amygdala (BLA. Recent work indicates that, like unconditioned emotional stimuli, exposure to an aversive conditioned stimulus (CS (i.e., a tone previously paired with shock can also enhance consolidation of DLS-dependent habit memory. The present experiments examined whether noradrenergic activity, particularly within the BLA, is required for a fear CS to enhance habit memory consolidation. First, rats underwent a fear conditioning procedure in which a tone CS was paired with an aversive unconditioned stimulus. Over the course of the next five days, rats received training in a DLS-dependent water plus-maze task, in which rats were reinforced to make a consistent body-turn response to reach a hidden escape platform. Immediately after training on days 1–3, rats received post-training systemic (Experiment 1 or intra-BLA (Experiment 2 administration of the β-adrenoreceptor antagonist, propranolol. Immediately after drug administration, half of the rats were re-exposed to the tone CS in the conditioning context (without shock. Post-training CS exposure enhanced consolidation of habit memory in vehicle-treated rats, and this effect was blocked by peripheral (Experiment 1 or intra-BLA (Experiment 2 propranolol administration. The present findings reveal that noradrenergic activity within the BLA is critical for the enhancement of DLS-dependent habit memory as a result of exposure to conditioned emotional stimuli.

  4. Prolonged Induction of miR-212/132 and REST Expression in Rat Striatum Following Cocaine Self-Administration.

    Science.gov (United States)

    Sadakierska-Chudy, Anna; Frankowska, Małgorzata; Miszkiel, Joanna; Wydra, Karolina; Jastrzębska, Joanna; Filip, Małgorzata

    2017-04-01

    Chronic exposure to cocaine in vivo induces long-term synaptic plasticity associated with the brain's circuitry that underlies development of repetitive and automatic behaviors called habits. In fact, prolonged drug consumption results in aberrant expression of protein-coding genes and small regulatory RNAs, including miRNAs that are involved in synaptic plasticity and neuroadaptations. However, the mechanisms mediating cocaine use disorder are still not fully understood. The present study is designed to examine the expression of miR-124, miR-132, miR-134, and miR-212, as well as the levels of the Ago2, Pum2, and REST mRNAs and proteins implicated in their regulation. We applied rat cocaine self-administration (SA) and extinction training procedures with a yoked triad to assess the changes in the levels of four miRNAs and three protein-coding genes and corresponding proteins in the dorsal striatum. We demonstrated that elevated expression of mature miR-212 and miR-132 is long-lasting and persists in the drug-free period (till 10-day abstinence). Moreover, mRNA and protein of REST, a regulator of neuronal transcription, was raised selectively in cocaine self-administering rats and Ago2 transcript decreased after cocaine treatment. Unexpectedly, the expression level of Ago2 and Pum2 proteins changed only in the active cocaine-receiving animals. These results point out the important aspects of long-lasting alterations in microRNAs, genes, and protein expressions involved in the control of synaptic plasticity associated with reward and motivation learning related to cocaine addiction.

  5. Morphological features, distribution and compartmental organization of the nicotinamide adenine dinucleotide phosphate reduced-diaphorase interneurons in the human striatum.

    Science.gov (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2005-08-29

    Striatal nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d)-positive (+) cells are one of the major classes of striatal interneurons. The present study analyzes their somatodendritic morphology, distribution pattern, and compartmental organization in the caudate nucleus (CN) and putamen (Put) of nine normal human brains. The following striatal territories are examined: 1) the precommissural head of the CN; 2) the postcommissural head of the CN; 3) the body of the CN; 4) the gyrus of the CN; 5) the tail of the CN; 6) the precommissural Put; and 7) the postcommissural Put. Three morphologically distinct types of NADPH-d+ neurons were found in each of these territories. The two most common NADPH-d+ neurons displayed an ovoid or triangular perikaryon from which several thick primary dendrites emerged, although much less numerous, bipolar-shaped NADPH-d+ cells were also observed. The highest density of NADPH-d+ neurons was found in the gyrus of the CN, followed by the body of the CN, tail of the CN, postcommissural head of the CN, postcommissural Put, precommissural head of the CN, and precommissural Put. The matrix was the striatal compartment with the densest NADPH-d+ neuronal population. Some of these cells also occurred in the center and peripheral regions of the striosomes located in the head of the CN and in the Put. In the body and gyrus of the CN, the striosomes were largely devoid of these striatal interneurons. Knowledge of the density and distribution of these interneurons should advance our understanding of the organization of the normal human striatum and help to evaluate the effects of neurodegenerative processes on cell density. (c) 2005 Wiley-Liss, Inc.

  6. The Dorsal Striatum and the Dynamics of the Consensus Connectomes in the Frontal Lobe of the Human Brain.

    Science.gov (United States)

    Kerepesi, Csaba; Varga, Bálint; Szalkai, Balázs; Grolmusz, Vince

    2018-02-26

    In the applications of the graph theory, it is unusual that one considers numerous, pairwise different graphs on the very same set of vertices. In the case of human braingraphs or connectomes, however, this is the standard situation: the nodes correspond to anatomically identified cerebral regions, and two vertices are connected by an edge if a diffusion MRI-based workflow identifies a fiber of axons, running between the two regions, corresponding to the two vertices. Therefore, if we examine the braingraphs of n subjects, then we have n graphs on the very same, anatomically identified vertex set. It is a natural idea to describe the k-frequently appearing edges in these graphs: the edges that are present between the same two vertices in at least k out of the n graphs. Based on the NIH-funded large Human Connectome Project's public data release, we have reported the construction of the Budapest Reference Connectome Server http://www.connectome.pitgroup.org that generates and visualizes these k-frequently appearing edges. We call the graphs of the k-frequently appearing edges "k-consensus connectomes" since an edge could be included only if it is present in at least k graphs out of n. Considering the whole human brain, we have reported a surprising property of these consensus connectomes earlier. In the present work we are focusing on the frontal lobe of the brain, and we report here a similarly surprising dynamical property of the consensus connectomes when k is gradually changed from k=n to k=1: the connections between the nodes of the frontal lobe are seemingly emanating from those nodes that were connected to sub-cortical structures of the dorsal striatum: the caudate nucleus, and the putamen. We hypothesize that this dynamic behavior copies the axonal fiber development of the frontal lobe. An animation of the phenomenon is presented at https://youtu.be/wBciB2eW6_8. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. T151. APATHY AND DIMINISHED EXPRESSION ARE NOT ASSOCIATED WITH VENTRAL OR DORSAL STRIATUM VOLUME IN SCHIZOPHRENIA

    Science.gov (United States)

    Burrer, Achim; Kirschner, Matthias; Seifritz, Erich; Stefan, Kaiser

    2018-01-01

    Abstract Background Negative symptoms are core features of schizophrenia and can be grouped into two domains. These are apathy including anhedonia, avolition and asocialty as well as diminished expression including blunted affect and alogia. A large body of research found that ventral striatal hypoactivation is linked to negative symptoms. In particular, it has been shown that this neural correlate is specific for apathy but not diminished expression. Here, we investigated whether this dissociation can also be found in ventral striatum volume. Methods We included brain structural T1 MRI data of 60 patients diagnosed with schizophrenia (SZ) and 58 healthy controls (HC). Negative symptoms in these groups have been assessed using the Brief Negative Symptom Scale (BNSS). We performed voxel-based morphometry (VBM) using the statistical parametric mapping package (SPM 12; Wellcome Trust Centre for Neuroimaging, London). We performed a region of interest (ROI) analysis of ventral and dorsal striatal volume between patients with schizophrenia and healthy controls. Furthermore, we analyzed the correlation of right and left ventral striatal volume with apathy and diminished expression in patients with schizophrenia. Moreover, we analyzed potential group differences in gray matter volume in an exploratory whole-brain analysis. Finally, we performed an exploratory whole-brain linear regression to identify potential correlations between the two negative symptom dimensions and gray matter volume. (cluster-defining threshold of p < 0.001, cluster-level pFWE < 0.05) Results Patients with schizophrenia showed no differences in ventral striatal volume compared to healthy controls. Apathy or diminished expression did not correlate with ventral or dorsal striatal gray matter volume in patients with schizophrenia. In the exploratory whole-brain analysis we found significant less gray matter volume in the right insula of schizophrenia patients compared to healthy controls (cluster

  8. Effect of Withania somnifera supplementation on rotenone-induced oxidative damage in cerebellum and striatum of the male mice brain.

    Science.gov (United States)

    Manjunath, Mallaya Jayawanth; Muralidhara

    2013-03-01

    Withania somnifera (WS) an ayurvedic medicinal herb is widely known for its memory enhancing ability and improvement of brain function. In the present study, we tested the hypothesis that WS prophylaxis could offset neurotoxicant-induced oxidative dysfunctions in developing brain employing a rotenone (ROT) mouse model. Initially, we assessed the potential of WS oral supplements (100-400 mg/ kg b.w/ d, 4wks) to modulate the endogenous levels of oxidative markers in cerebellum (cb) and striatum (st) of prepubertal (PP) mice. Further, we assessed the induction of oxidative stress in cb and st of mice administered with ROT (i.p. 0.5 and 1mg/ kg b.w, 7d). ROT caused significant elevation in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), hydroperoxides (HP) and nitric oxide (NO) levels in both brain regions. Further ROT caused significant perturbations in the levels of reduced glutathione (GSH), activity levels of antioxidant enzymes, acetylcholinesterase and mitochondrial dysfunctions suggesting a state of oxidative stress. In a satellite study, we examined the protective effects of WS root powder (400mg/ kg b.w/ d, 4wks) in PP mice challenged with ROT (0.5 mg/ kg b.w/ d, 7 d). WS prophylaxis significantly offset ROT-induced oxidative damage in st and cb as evident by the normalized levels of oxidative markers (MDA, ROS levels and HP) and restoration of depleted GSH levels. Further, WS effectively normalized the NO levels in both brain regions suggesting its antiinflammatory action. Furthermore, WS prophylaxis restored the activity levels of cytosolic antioxidant enzymes, neurotransmitter function and dopamine levels in st. Taken together, these findings suggest that WS prophylaxis has the propensity to modulate neurotoxicant-mediated oxidative impairments and mitochondrial dysfunctions in specific brain regions of mice. While the exact mechanism/s underlying the neuroprotective effects of WS merit further investigation, based on our findings, we

  9. Increased L-DOPA-derived dopamine following selective MAO-A or-B inhibition in rat striatum depleted of dopaminergic and serotonergic innervation

    Science.gov (United States)

    Sader-Mazbar, O; Loboda, Y; Rabey, M J; Finberg, J P M

    2013-01-01

    Background and Purpose Selective MAO type B (MAO-B) inhibitors are effective in potentiation of the clinical effect of L-DOPA in Parkinson's disease, but dopamine (DA) is deaminated mainly by MAO type A (MAO-A) in rat brain. We sought to clarify the roles of MAO-A and MAO-B in deamination of DA formed from exogenous L-DOPA in rat striatum depleted of dopaminergic, or both dopaminergic and serotonergic innervations. We also studied the effect of organic cation transporter-3 (OCT-3) inhibition by decinium-22 on extracellular DA levels following L-DOPA. Experimental Approach Striatal dopaminergic and/or serotonergic neuronal innervations were lesioned by 6-hydroxydopamine or 5,7-dihydroxytryptamine respectively. Microdialysate DA levels after systemic L-DOPA were measured after inhibition of MAO-A or MAO-B by clorgyline or rasagiline respectively. MAO subtype localization in the striatum was determined by immunofluorescence. Key Results Rasagiline increased DA extracellular levels following L-DOPA to a greater extent in double-than in single-lesioned rats (2.8-and 1.8-fold increase, respectively, relative to saline treatment); however, clorgyline elevated DA levels in both models over 10-fold. MAO-A was strongly expressed in medium spiny neurons (MSNs) in intact and lesioned striata, while MAO-B was localized in glia and to a small extent in MSNs. Inhibition of OCT-3 increased DA levels in the double-more than the single-lesion animals. Conclusions and Implications In striatum devoid of dopaminergic and serotonergic inputs, most deamination of L-DOPA-derived DA is mediated by MAO-A in MSN and a smaller amount by MAO-B in both MSN and glia. OCT-3 plays a significant role in uptake of DA from extracellular space. Inhibitors of OCT-3 are potential future targets for anti-Parkinsonian treatments. PMID:23992249

  10. A translational murine model of sub-lethal intoxication with Shiga toxin 2 reveals novel ultrastructural findings in the brain striatum.

    Directory of Open Access Journals (Sweden)

    Carla Tironi-Farinati

    Full Text Available Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS, acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin.

  11. Time-dependent effects of repeated THC treatment on dopamine D2/3 receptor-mediated signalling in midbrain and striatum.

    Science.gov (United States)

    Tournier, Benjamin B; Tsartsalis, Stergios; Dimiziani, Andrea; Millet, Philippe; Ginovart, Nathalie

    2016-09-15

    This study examined the time-course of alterations in levels and functional sensitivities of dopamine D2/3 receptors (D2/3R) during the course and up to 6 weeks following cessation of chronic treatment with Delta(9)-Tetrahydrocannabinol (THC) in rats. THC treatment led to an increase in D2/3R levels in striatum, as assessed using [(3)H]-(+)-PHNO, that was readily observable after one week of treatment, remained stably elevated during the subsequent 2 weeks of treatment, but fully reversed within 2 weeks of THC discontinuation. THC-induced D2/3R alterations were more pronounced and longer lasting in the dopamine cell body regions of the midbrain, wherein [(3)H]-(+)-PHNO binding was still elevated at 2 weeks but back to control values at 6 weeks after THC cessation. Parallel analyses of the psychomotor effects of pre- and post-synaptic doses of quinpirole also showed a pattern of D2/3R functional supersensitivity indicative of more rapid subsidence in striatum than in midbrain following drug cessation. These results indicate that chronic THC is associated with a biochemical and functional sensitization of D2/3R signaling, that these responses show a region-specific temporal pattern and are fully reversible following drug discontinuation. These results suggest that an increased post-synaptic D2/3R function and a decreased DA presynaptic signaling, mediated by increased D2/3R autoinhibition, may predominate during distinct phases of withdrawal and may contribute both to the mechanisms leading to relapse and to cannabinoid withdrawal symptoms. The different rates of normalization of D2/3R function in striatum and midbrain may be critical information for the development of new pharmacotherapies for cannabis dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Regulation of synaptic MAPK/ERK phosphorylation in the rat striatum and medial prefrontal cortex by dopamine and muscarinic acetylcholine receptors.

    Science.gov (United States)

    Xue, Bing; Mao, Li-Min; Jin, Dao-Zhong; Wang, John Q

    2015-10-01

    Dopamine and acetylcholine are two principal transmitters in the striatum and are usually balanced to modulate local neural activity and to maintain striatal homeostasis. This study investigates the role of dopamine and muscarinic acetylcholine receptors in the regulation of a central signaling protein, i.e., the mitogen-activated protein kinase (MAPK). We focus on the synaptic pool of MAPKs because of the fact that these kinases reside in peripheral synaptic structures in addition to their somatic locations. We show that a systemic injection of dopamine D1 receptor (D1R) agonist SKF81297 enhances phosphorylation of extracellular signal-regulated kinases (ERKs), a prototypic subclass of MAPKs, in the adult rat striatum. Similar results were observed in another dopamine-responsive region, the medial prefrontal cortex (mPFC). The dopamine D2 receptor agonist quinpirole had no such effects. Pretreatment with a positive allosteric modulator (PAM) of muscarinic acetylcholine M4 receptors (M4Rs), VU0152100, attenuated the D1R agonist-stimulated ERK phosphorylation in the two regions, whereas the PAM itself did not alter basal ERK phosphorylation. All drug treatments had no effect on phosphorylation of c-Jun N-terminal kinases (JNKs), another MAPK subclass, in the striatum and mPFC. These results demonstrate that dopamine and acetylcholine are integrated to control synaptic ERK but not JNK activation in striatal and mPFC neurons in vivo. Activation of M4Rs exerts an inhibitory effect on the D1R-mediated upregulation of synaptic ERK phosphorylation. © 2015 Wiley Periodicals, Inc.

  13. Functional volumetric analysis of striatum using F-18 FP-CIT PET in patients with idiopathic Parkinson's disease and normal subjects.

    Science.gov (United States)

    Jeong, Young Jin; Son, Hye Joo; Yoon, Hyun Jin; Kang, Do-Young

    2016-10-01

    We applied a simple isocontour volume-of-interest (VOI) method to analyze the whole striatum in an F-18 FP-CIT PET image and to investigate the usefulness of the method in differentiating healthy subjects from idiopathic Parkinson's disease (IPD) patients and the correlation of the value of functional volume parameters with the motor symptoms in patients with IPD. Forty-three IPD patients and 23 age-matched healthy controls underwent F-18 FP-CIT PET. Using a dedicated workstation, VOIs for the whole striatum were drawn automatically with the gradient delineation method. The SUVmax, SUVmean, functional volume (FV), striatal volume activity (SVA), striatal-specific binding (SSB), and volume-specific uptake ratio (VSUR) were compared between the IPD patients and the normal subjects. In the IPD patients, the correlation between the clinical factor and the functional parameters was assessed. The SUVmax, SUVmean, FV, SVA, SSB, and VSUR were significantly lower in the IPD patients than in the normal subjects. In the receiver operating characteristic analysis, those parameters had significant and good-to-excellent accuracy. In the patients with IPD, a moderate negative correlation was revealed between the SUVmax and H&Y stage, the SUVmean and H&Y stage, SVA and H&Y stage, the VSUR and H&Y stage, the FV and bradykinesia, and the SVA and bradykinesia. The functional volumetric analysis of the striatum based on simple isocontour VOI was a useful method of analyzing the F-18 FP-CIT PET image. Not only can it be easily applied in daily clinical practice, but it can also be used as a clinical parameter to discriminate IPD and to correlate it with the disease severity.

  14. Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

    Science.gov (United States)

    Tamakoshi, Keigo; Ishida, Akimasa; Takamatsu, Yasuyuki; Hamakawa, Michiru; Nakashima, Hiroki; Shimada, Haruka; Ishida, Kazuto

    2014-03-01

    We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Silencing the critics: understanding the effects of cocaine sensitization on dorsolateral and ventral striatum in the context of an Actor/Critic model

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available A critical problem in daily decision making is how to choose actions now in order to bring about rewards later. Indeed, many of our actions have long-term consequences, and it is important to not be myopic in balancing the pros and cons of different options, but rather to take into account both immediate and delayed consequences of actions. Failures to do so may be manifest as persistent, maladaptive decision-making, one example of which is addiction where behavior seems to be driven by the immediate positive experiences with drugs, despite the delayed adverse consequences. A recent study by Takahashi et al. (2007 investigated the effects of cocaine sensitization on decision making in rats and showed that drug use resulted in altered representations in the ventral striatum and the dorsolateral striatum, areas that have been implicated in the neural instantiation of a computational solution to optimal long-term actions selection called the Actor/Critic framework. In this Focus article we discuss their results and offer a computational interpretation in terms of drug-induced impairments in the Critic. We first survey the different lines of evidence linking the subparts of the striatum to the Actor/Critic framework, and then suggest two possible scenarios of breakdown that are suggested by Takahashi et al’s data. As both are compatible with the current data, we discuss their different predictions and how these could be empirically tested in order to further elucidate (and hopefully inch towards curing the neural basis of drug addiction.

  16. Different locomotor sensitization responses to repeated cocaine injections are associated with differential phosphorylation of GluA1 in the dorsomedial striatum of adult rats.

    Science.gov (United States)

    Kim, Myonghwan; Kim, Wonju; Baik, Ja-Hyun; Yoon, Bong-June

    2013-11-15

    Behavioral sensitization to psychostimulants reflects neural adaptation, which might share a common mechanism with drug addiction. Outbred male rats show different locomotor sensitization responses to cocaine, and cocaine also produces varied addictive progress in humans. We investigated whether differences in the induction of sensitization would affect the long-term persistence of sensitized locomotor activity, and we sought to determine the molecular basis for the variability in sensitization. Male Sprague-Dawley rats that showed sensitized locomotor responses over 5 consecutive daily cocaine injections (SENS) had significantly lower initial locomotor responses to the 1st cocaine exposure than did rats that did not show locomotor sensitization (NONS). Furthermore, rats that underwent 1 month of cocaine withdrawal after 5 repeated cocaine injections also exhibited sensitized or non-sensitized locomotor responses to a challenge injection of cocaine (SENS-C or NONS-C, respectively). This variability was also related to the initial responsiveness to cocaine. We examined the level of phosphorylation of the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropioniate receptor (AMPAR) in the dorsal striatum and found that there were significant differences between the sensitized rats and the non-sensitized rats. pGluA1-Ser831 was increased in the SENS rats during the induction of locomotor sensitization, and pGluA1-Ser845 was increased in the SENS-C rats during the expression of locomotor sensitization. These phosphorylation changes were observed in the dorsomedial striatum (DMS) of adult rats but not in the dorsolateral striatum (DLS) of adults. Our findings suggest that differential phosphorylation of AMPAR might be an important mechanism that contributes to the development of locomotor sensitization to cocaine in adult rats. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder<