WorldWideScience

Sample records for sublaterodorsal tegmental nucleus

  1. Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder.

    Science.gov (United States)

    Valencia Garcia, Sara; Libourel, Paul-Antoine; Lazarus, Michael; Grassi, Daniela; Luppi, Pierre-Hervé; Fort, Patrice

    2017-02-01

    SEE SCHENCK AND MAHOWALD DOI101093/AWW329 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Idiopathic REM sleep behaviour disorder is characterized by the enactment of violent dreams during paradoxical (REM) sleep in the absence of normal muscle atonia. Accumulating clinical and experimental data suggest that REM sleep behaviour disorder might be due to the neurodegeneration of glutamate neurons involved in paradoxical sleep and located within the pontine sublaterodorsal tegmental nucleus. The purpose of the present work was thus to functionally determine first, the role of glutamate sublaterodorsal tegmental nucleus neurons in paradoxical sleep and second, whether their genetic inactivation is sufficient for recapitulating REM sleep behaviour disorder in rats. For this goal, we first injected two retrograde tracers in the intralaminar thalamus and ventral medulla to disentangle neuronal circuits in which sublaterodorsal tegmental nucleus is involved; second we infused bilaterally in sublaterodorsal tegmental nucleus adeno-associated viruses carrying short hairpin RNAs targeting Slc17a6 mRNA [which encodes vesicular glutamate transporter 2 (vGluT2)] to chronically impair glutamate synaptic transmission in sublaterodorsal tegmental nucleus neurons. At the neuroanatomical level, sublaterodorsal tegmental nucleus neurons specifically activated during paradoxical sleep hypersomnia send descending efferents to glycine/GABA neurons within the ventral medulla, but not ascending projections to the intralaminar thalamus. These data suggest a crucial role of sublaterodorsal tegmental nucleus neurons rather in muscle atonia than in paradoxical sleep generation. In line with this hypothesis, 30 days after adeno-associated virus injections into sublaterodorsal tegmental nucleus rats display a decrease of 30% of paradoxical sleep daily quantities, and a significant increase of muscle tone during paradoxical sleep concomitant to a tremendous increase of abnormal motor dream

  2. Neurophysiological evidence for the presence of cannabinoid CB1 receptors in the laterodorsal tegmental nucleus

    DEFF Research Database (Denmark)

    Soni, Neeraj; Satpathy, Shankha; Kohlmeier, Kristi Anne

    2014-01-01

    Marijuana, which acts within the endocannabinoid (eCB) system as an agonist of the cannabinoid type 1 receptor (CB1R), exhibits addictive properties and has powerful actions on the state of arousal of an organism. The laterodorsal tegmental nucleus (LDT), as a component of the reticular activating...

  3. Cardiovascular effects of nitrergic system of the pedunculopon-tine tegmental nucleus in anesthetized rats

    Directory of Open Access Journals (Sweden)

    Mohammad Naser Shafei

    2017-07-01

    Full Text Available Objective(s: Nitric oxide (NO is an important neurotransmitter in central nervous system involved in central cardiovascular regulation. The presence of NO in the pedunculopontine tegmental (PPT nucleus has been shown, but its cardiovascular effect has not been determined. In the present study, the cardiovascular effect of NO in the PPT nucleus was evaluated. Materials and Methods: After induction of anesthesia, a polyethylene catheter (PE-50 filled with heparinized saline inserted into the femoral artery, and the blood pressure (BP and heart rate (HR were continuously recorded. Animals were then placed in a stereotaxic apparatus and maximum changes of mean arterial pressure (∆MAP and heart rate (∆HR after microinjection of two doses of NG-nitro-L-arginine methyl ester (L-NAME, 30 and 90 nmol, L-arginine (L-Arg 10 and 50 nmol and sodium nitroprusside (SNP, 9 and 27 nmol into the PPT were provided and compared with control group (One-way ANOVA. Results: Both doses of L-NAME significantly increased ∆MAP compared to control (PP

  4. The pedunculopontine tegmental nucleus as a motor and cognitive interface between the cerebellum and basal ganglia

    Directory of Open Access Journals (Sweden)

    Fumika Mori

    2016-11-01

    Full Text Available As an important component of ascending activating systems, brainstem cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg are involved in the regulation of motor control (locomotion, posture and gaze and cognitive processes (attention, learning, and memory. The PPTg is highly interconnected with several regions of the basal ganglia, and one of its key functions is to regulate and relay activity from the basal ganglia. Together, they have been implicated in the motor control system (such as voluntary movement initiation or inhibition, and modulate aspects of executive function (such as motivation. In addition to its intimate connection with the basal ganglia, projections from the PPTg to the cerebellum have been recently reported to synaptically activate the deep cerebellar nuclei. Classically, the cerebellum and basal ganglia were regarded as forming separated anatomical loops that play a distinct functional role in motor and cognitive behavioral control. Here, we suggest that the PPTg may also act as an interface device between the basal ganglia and cerebellum. As such, part of the therapeutic effect of PPTg deep brain stimulation to relieve gait freezing and postural instability in advanced Parkinson’s disease patients might also involve modulation of the cerebellum. We review the anatomical position and role of the PPTg in the pathway of basal ganglia and cerebellum in relation to motor control, cognitive function, and Parkinson’s disease.

  5. Intrinsic connectivity between the hippocampus, nucleus accumbens, and ventral tegmental area in humans.

    Science.gov (United States)

    Kahn, I; Shohamy, D

    2013-03-01

    Recent studies suggest that memory formation in the hippocampus is modulated by the motivational significance of events, allowing past experience to adaptively guide behavior. The effects of motivation on memory are thought to depend on interactions between the hippocampus, the ventral tegmental area (VTA), and the nucleus accumbens (NAcc). Indeed, animal studies reveal anatomical pathways for circuit-level interaction between these regions. However, a homologue circuit connectivity in humans remains to be shown. We characterized this circuitry in humans by exploiting spontaneous low-frequency modulations in the fMRI signal (termed resting-state functional connectivity), which are thought to reflect functionally related regions and their organization into functional networks in the brain. We examined connectivity in this network across two datasets (hi-resolution, n = 100; standard resolution, n = 894). Results reveal convergent connectivity between the hippocampus, and both the NAcc and the VTA centered on ventral regions in the body of the hippocampus. Additionally, we found individual differences in the strength of connectivity within this network. Together, these results provide a novel task-independent characterization of circuitry underlying interactions between the hippocampus, NAcc, and VTA and provide a framework with which to understand how connectivity might reflect and constrain the effects of motivation on memory. Copyright © 2012 Wiley Periodicals, Inc.

  6. Role of the pedunculopontine tegmental nucleus in sensorimotor gating and reward-related behavior in rats.

    Science.gov (United States)

    Diederich, Kai; Koch, Michael

    2005-05-01

    The pedunculopontine tegmental nucleus (PPTg) is involved in the execution and regulation of a variety of behaviors. Most investigations used brain lesions that have certain disadvantages, such as functional compensation over time. In the present study, we investigated by temporary, reversible inhibition of neurons the role of the PPTg in sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR) using variable interstimulus intervals (ISI). In a second set of experiments we examined by the same technique the role of the PPTg in a progressive-ratio instrumental response task. Local infusions of the GABA(A)-receptor agonist muscimol (0.05 microg and 0.5 microg/0.3 microl, or vehicle) were applied through indwelling microinfusion cannulae into the PPTg of freely moving rats. ASR and PPI were measured using acoustic stimuli of 100 dB (pulse) and 80 dB (prepulse) using ISIs of 25, 120, 520 and 1,020 ms. Instrumental behavior (lever pressing for casein pellets) was assessed in a Skinner box. Motor activity was measured in an open field. Intra-PPTg infusions of muscimol dose-dependently attenuated PPI at ISIs of 120 ms and 520 ms, but not at longer or shorter ISIs. ASR magnitude in pulse-alone trials was not significantly affected. Intra-PPTg infusion of 0.5 microg muscimol reduced the break point of instrumental responding (testing sequence where the rats fail to respond according to an increased ratio of reinforcement). No effects on food-preference and open-field activity were found. These findings suggest that GABAergic neurotransmission in the PPTg plays an important role for sensorimotor gating at intermediate ISIs and for response selection under demanding schedules of reinforcement.

  7. Pedunculopontine tegmental nucleus lesions impair probabilistic reversal learning by reducing sensitivity to positive reward feedback.

    Science.gov (United States)

    Syed, Anam; Baker, Phillip M; Ragozzino, Michael E

    2016-05-01

    Recent findings indicate that pedunculopontine tegmental nucleus (PPTg) neurons encode reward-related information that is context-dependent. This information is critical for behavioral flexibility when reward outcomes change signaling a shift in response patterns should occur. The present experiment investigated whether NMDA lesions of the PPTg affects the acquisition and/or reversal learning of a spatial discrimination using probabilistic reinforcement. Male Long-Evans rats received a bilateral infusion of NMDA (30nmoles/side) or saline into the PPTg. Subsequently, rats were tested in a spatial discrimination test using a probabilistic learning procedure. One spatial location was rewarded with an 80% probability and the other spatial location rewarded with a 20% probability. After reaching acquisition criterion of 10 consecutive correct trials, the spatial location - reward contingencies were reversed in the following test session. Bilateral and unilateral PPTg-lesioned rats acquired the spatial discrimination test comparable to that as sham controls. In contrast, bilateral PPTg lesions, but not unilateral PPTg lesions, impaired reversal learning. The reversal learning deficit occurred because of increased regressions to the previously 'correct' spatial location after initially selecting the new, 'correct' choice. PPTg lesions also reduced the frequency of win-stay behavior early in the reversal learning session, but did not modify the frequency of lose-shift behavior during reversal learning. The present results suggest that the PPTg contributes to behavioral flexibility under conditions in which outcomes are uncertain, e.g. probabilistic reinforcement, by facilitating sensitivity to positive reward outcomes that allows the reliable execution of a new choice pattern. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The pedunculopontine tegmental nucleus and the nucleus basalis magnocellularis: Do both have a role in sustained attention?

    Directory of Open Access Journals (Sweden)

    Latimer Mary P

    2008-01-01

    Full Text Available Abstract Background It is well established that nucleus basalis magnocellularis (NbM lesions impair performance on tests of sustained attention. Previous work from this laboratory has also demonstrated that pedunculopontine tegmental nucleus (PPTg lesioned rats make more omissions on a test of sustained attention, suggesting that it might also play a role in mediating this function. However, the results of the PPTg study were open to alternative interpretation. We aimed to resolve this by conducting a detailed analysis of the effects of damage to each brain region in the same sustained attention task used in our previous work. Rats were trained in the task before surgery and post-surgical testing examined performance in response to unpredictable light signals of 1500 ms and 4000 ms duration. Data for PPTg lesioned rats were compared to control rats, and rats with 192 IgG saporin infusions centred on the NbM. In addition to operant data, video data of rats' performance during the task were also analysed. Results Both lesion groups omitted trials relative to controls but the effect was milder and transient in NbM rats. The number of omitted trials decreased in all groups when tested using the 4000 ms signal compared to the 1500 ms signal. This confirmed previous findings for PPTg lesioned rats. Detailed analysis revealed that the increase in omissions in PPTg rats was not a consequence of motor impairment. The video data (taken on selected days showed reduced lever orientation in PPTg lesioned rats, coupled with an increase in unconditioned behaviours such as rearing and sniffing. In contrast NbM rats showed evidence of inadequate lever pressing. Conclusion The question addressed here is whether the PPTg and NbM both have a role in sustained attention. Rats bearing lesions of either structure showed deficits in the test used. However, we conclude that the most parsimonious explanation for the deficit observed in PPTg rats is inadequate response

  9. Increased CRF signaling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal

    Science.gov (United States)

    Zhao-Shea, Rubing; DeGroot, Steven R.; Liu, Liwang; Vallaster, Markus; Pang, Xueyan; Su, Qin; Gao, Guangping; Rando, Oliver J.; Martin, Gilles E.; George, Olivier; Gardner, Paul D.; Tapper, Andrew R.

    2015-01-01

    Increased anxiety is a predominant withdrawal symptom in abstinent smokers, yet the neuroanatomical and molecular bases underlying it are unclear. Here, we show that withdrawal-induced anxiety increases activity of neurons in the interpeduncular intermediate (IPI), a subregion of the interpeduncular nucleus (IPN). IPI activation during nicotine withdrawal was mediated by increased corticotropin releasing factor (CRF) receptor-1 expression and signaling, which modulated glutamatergic input from the medial habenula (MHb). Pharmacological blockade of IPN CRF1 receptors or optogenetic silencing of MHb input reduced IPI activation and alleviated withdrawal-induced anxiety; whereas IPN CRF infusion in mice increased anxiety. We identified a meso-interpeduncular circuit, consisting of ventral tegmental area (VTA) dopaminergic neurons projecting to the IPN, as a potential source of CRF. Knock-down of CRF synthesis in the VTA prevented IPI activation and anxiety during nicotine withdrawal. These data indicate that increased CRF receptor signaling within a VTA-IPN-MHb circuit triggers anxiety during nicotine withdrawal. PMID:25898242

  10. Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

    Directory of Open Access Journals (Sweden)

    Stephan Steidl

    Full Text Available Cholinergic input to the ventral tegmental area (VTA is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII, the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

  11. Endogenous GDNF in ventral tegmental area and nucleus accumbens does not play a role in the incubation of heroin craving.

    Science.gov (United States)

    Airavaara, Mikko; Pickens, Charles L; Stern, Anna L; Wihbey, Kristina A; Harvey, Brandon K; Bossert, Jennifer M; Liu, Qing-Rong; Hoffer, Barry J; Shaham, Yavin

    2011-04-01

    Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were paired with a tone-light cue) and tested for cue-induced heroin-seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time-dependent increases in extinction responding were associated with time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens. Additionally, acute accumbens (but not VTA) GDNF injections (12.5 µg/side) administered 1-3 hours after the last heroin self-administration training session enhanced the time-dependent increases in extinction responding after withdrawal. However, the time-dependent increases in extinction responding after withdrawal were not associated with changes in GDNF protein expression in VTA and accumbens. Additionally, interfering with endogenous GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies (600 ng/side/day) into VTA or accumbens had no effect on the time-dependent increases in extinction responding. In summary, heroin self-administration and withdrawal regulate VTA and accumbens GDNF mRNA expression in a time-dependent manner, and exogenous GDNF administration into accumbens but not VTA potentiates cue-induced heroin seeking. However, based on the GDNF protein expression and the anti-GDNF monoclonal neutralizing antibodies manipulation data, we conclude that neither accumbens nor VTA endogenous GDNF mediates the incubation of heroin craving. © 2010 Society for the Study of Addiction. No claim to original US government works.

  12. Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior.

    Science.gov (United States)

    Kamii, Hironori; Kurosawa, Ryo; Taoka, Naofumi; Shinohara, Fumiya; Minami, Masabumi; Kaneda, Katsuyuki

    2015-05-01

    The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus implicated in reward processing and is one of the main sources of cholinergic afferents to the ventral tegmental area (VTA). Neuroplasticity in this structure may affect the excitability of VTA dopamine neurons and mesocorticolimbic circuitry. Here, we provide evidence that cocaine-induced intrinsic membrane plasticity in LDT cholinergic neurons is involved in addictive behaviors. After repeated experimenter-delivered cocaine exposure, ex vivo whole-cell recordings obtained from LDT cholinergic neurons revealed an induction of intrinsic membrane plasticity in regular- but not burst-type neurons, resulting in increased firing activity. Pharmacological examinations showed that increased riluzole-sensitive persistent sodium currents, but not changes in Ca(2+) -activated BK, SK or voltage-dependent A-type potassium conductance, mediated this plasticity. In addition, bilateral microinjection of riluzole into the LDT immediately before the test session in a cocaine-induced conditioned place preference (CPP) paradigm inhibited the expression of cocaine-induced CPP. These findings suggest that intrinsic membrane plasticity in LDT cholinergic neurons is causally involved in the development of cocaine-induced addictive behaviors. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Deep brain stimulation of pedunculopontine tegmental nucleus: role in sleep modulation in advanced Parkinson disease patients: one-year follow-up.

    Science.gov (United States)

    Peppe, Antonella; Pierantozzi, Mariangela; Baiamonte, Valentina; Moschella, Vincenzo; Caltagirone, Carlo; Stanzione, Paolo; Stefani, Alessandro

    2012-12-01

    Sleep disorders are frequent non-motor symptoms in Parkinson disease (PD), probably due to multifactorial pathogeneses including disease progression, dopaminergic drugs, or concomitant illness. In recent years, the pedunculopontine tegmental (PPTg) nucleus has been considered a surgical target for deep brain stimulation (DBS) in advanced PD patients. As it is involved in controlling the sleep-wake cycle, we investigated the long-lasting effects of PPTg-DBS on the sleep of five PD patients implanted in both the PPTg and the subthalamic nucleus (STN) by rating two subjective clinical scales for sleep: the Parkinson's Disease Sleep Scale (PDSS), and the Epworth Sleepiness Scale (ESS). Sleep scales were administered a week before surgery (T0), three months after DBS (T1), and one year later (T2). In this study, STN-DBS was kept constantly in ON, and three different patterns of PPTg-DBS were investigated: STN-ON (PPTg switched off); PPTg-ON (PPTg stimulated 24 h/day); PPTg-cycle (PPTg stimulated only at night). In post-surgery follow-up, PD patients reported a marked improvement of sleep quality in all DBS conditions. In particular, stimulation of the PPTg nucleus produced not only a remarkable long-term improvement of nighttime sleep, but unlike STN-DBS, also produced significant amelioration of daytime sleepiness. Our study suggests that PPTg-DBS plays an important role in reorganizing regular sleep in PD patients.

  14. Endocannabinoid CB1 Receptor Mediated Rises in Ca2+ and Depolarization-Induced Suppression of Inhibition within the Laterodorsal Tegmental Nucleus

    DEFF Research Database (Denmark)

    Soni, Neeraj; Kohlmeier, Kristi Anne

    2016-01-01

    Cannabinoid type 1 receptors (CB1Rs) are functionally active within the laterodorsal tegmental nucleus (LDT), which is critically involved in control of rapid eye movement sleep, cortical arousal, and motivated states. To further characterize the cellular consequences of activation of CB1Rs...... in this nucleus, we examined whether CB1R activation led to rises in intracellular Ca(2+) ([Ca(2+)]i) and whether processes shown in other regions to involve endocannabinoid (eCB) transmission were present in the LDT. Using a combination of Ca(2+) imaging in multiple cells loaded with Ca(2+) imaging dye via 'bulk......-loading' or in single cells loaded with dye via a patch-clamp electrode, we found that WIN 55212-2 (WIN-2), a potent CB1R agonist, induced increases in [Ca(2+)]i which were sensitive to AM251, a CB1R antagonist. A proportion of rises persisted in TTX and/or low-extracellular Ca(2+) conditions. Attenuation...

  15. Decreased functional connectivity between ventral tegmental area and nucleus accumbens in Internet gaming disorder: evidence from resting state functional magnetic resonance imaging.

    Science.gov (United States)

    Zhang, Jin-Tao; Ma, Shan-Shan; Yip, Sarah W; Wang, Ling-Jiao; Chen, Chao; Yan, Chao-Gan; Liu, Lu; Liu, Ben; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

    2015-11-18

    Internet gaming disorder (IGD) has become an increasing mental health problem worldwide. Decreased resting-state functional connectivity (rsFC) between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) has been found in substance use and is thought to play an important role in the development of substance addiction. However, rsFC between the VTA and NAcc in a non-substance addiction, such as IGD, has not been assessed previously. The current study aimed to investigate: (1) if individuals with IGD exhibit alterations in VTA-NAcc functional connectivity; and (2) whether VTA-NAcc functional connectivity is associated with subjective Internet craving. Thirty-five male participants with IGD and 24 healthy control (HC) individuals participated in resting-state functional magnetic resonance imaging. Regions of interest (left NAcc, right NAcc and VTA) were selected based on the literature and were defined by placing spheres centered on Talairach Daemon coordinates. In comparison with HCs, individuals with IGD had significantly decreased rsFC between the VTA and right NAcc. Resting-state functional connectivity strength between the VTA and right NAcc was negatively correlated with self-reported subjective craving for the Internet. These results suggest possible neural functional similarities between individuals with IGD and individuals with substance addictions.

  16. Role of dopamine D2-like receptors within the ventral tegmental area and nucleus accumbens in antinociception induced by lateral hypothalamus stimulation.

    Science.gov (United States)

    Moradi, Marzieh; Yazdanian, Mohamadreza; Haghparast, Abbas

    2015-10-01

    Several lines of evidence have shown that stimulation of the lateral hypothalamus (LH) can induce antinociception. It has been indicated that hypothalamic orexinergic neurons send projections throughout the dopamine mesolimbic pathway. Functional interaction between the LH and the main area of the mesolimbic pathway such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc) implicates in pain modulation. Thus, in this study, we investigated the role of D2-like dopamine receptors within the VTA and NAc in the LH stimulation-induced antinociception. Male Wistar rats weighing 230-280 g were unilaterally implanted with two separate cannulae into the LH and VTA or NAc. Animals received intra-VTA (0.25, 1 and 4 μg/0.3 μl DMSO) and intra-accumbal (0.125, 0.25, 1 and 4 μg/0.5 μl DMSO) infusions of sulpiride as a selective D2-like receptor antagonist, prior to intra-LH carbachol (125 nM/rat) administration. In the tail-flick test, the antinociceptive effects were measured using a tail-flick algesiometer and represented as maximal possible effect (%MPE) within 5, 15, 30, 45 and 60 min after injections. Our results showed that intra-VTA and intra-accumbal sulpiride dose-dependently attenuated the LH stimulation-induced antinociception. However, the blockade of D2-like receptors within the NAc was more significant than that of the VTA. These findings show that D2-like dopamine receptors in these regions play an important role in the LH-mediated modulation of nociceptive information in the acute model of pain in the rats. It seems that this pain modulating system is more relevant to D2-like receptors in the nucleus accumbens. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse ventral tegmental area that project to nucleus accumbens and other mesolimbic targets.

    Science.gov (United States)

    Peris, Joanna; MacFadyen, Kaley; Smith, Justin A; de Kloet, Annette D; Wang, Lei; Krause, Eric G

    2017-04-01

    The mesolimbic dopamine (DA) circuitry determines which behaviors are positively reinforcing and therefore should be encoded in the memory to become a part of the behavioral repertoire. Natural reinforcers, like food and sex, activate this pathway, thereby increasing the likelihood of further consummatory, social, and sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward and OT-synthesizing neurons project to the ventral tegmental area (VTA) and nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT regulation of DA neurons within the VTA is sparse. To phenotype OT-receptor (OTR) expressing neurons originating within the VTA, we delivered Cre-inducible adeno-associated virus that drives the expression of fluorescent marker into the VTA of male mice that had Cre-recombinase driven by OTR gene expression. OTR-expressing VTA neurons project to NAc, prefrontal cortex, the extended amygdala, and other forebrain regions but less than 10% of these OTR-expressing neurons were identified as DA neurons (defined by tyrosine hydroxylase colocalization). Instead, almost 50% of OTR-expressing cells in the VTA were glutamate (GLU) neurons, as indicated by expression of mRNA for the vesicular GLU transporter (vGluT). About one-third of OTR-expressing VTA neurons did not colocalize with either DA or GLU phenotypic markers. Thus, OTR expression by VTA neurons implicates that OT regulation of reward circuitry is more complex than a direct action on DA neurotransmission. J. Comp. Neurol. 525:1094-1108, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats

    Science.gov (United States)

    Bruijnzeel, Adrie W.; Corrie, Lu W.; Rogers, Jessica A.; Yamada, Hidetaka

    2011-01-01

    There is evidence for a role of insulin and leptin in food intake, but the effects of these adiposity signals on the brain reward system are not well understood. Furthermore, the effects of insulin and leptin on food intake in females are underinvestigated. These studies investigated the role of insulin and leptin in the ventral tegmental area (VTA) and the arcuate hypothalamic nucleus (Arc) on food intake and brain reward function in female rats. The intracranial self-stimulation procedure was used to assess the effects of insulin and leptin on the reward system. Elevations in brain reward thresholds are indicative of a decrease in brain reward function. The bilateral administration of leptin into the VTA (15–500 ng/side) or Arc (15–150 ng/side) decreased food intake for 72 h. The infusion of leptin into the VTA or Arc resulted in weight loss during the first 48 (VTA) or 24 h (Arc) after the infusions. The administration of insulin (0.005–5 mU/side) into the VTA or Arc decreased food intake for 24 h but did not affect body weights. The bilateral administration of low, but not high, doses of leptin (15 ng/side) or insulin (0.005 mU/side) into the VTA elevated brain reward thresholds. Neither insulin nor leptin in the Arc affected brain reward thresholds. These studies suggest that a small increase in leptin or insulin levels in the VTA leads to a decrease in brain reward function. A relatively large increase in insulin or leptin levels in the VTA or Arc decreases food intake. PMID:21255613

  19. Age-related changes in functional postsynaptic nAChR subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction

    DEFF Research Database (Denmark)

    Christensen, Mark Holm; Kohlmeier, Kristi Anne

    2016-01-01

    The earlier an individual initiates cigarette smoking, the higher the likelihood of development of dependency to nicotine, the addictive ingredient in cigarettes. One possible mechanism underlying this higher addiction liability is an ontogenetically differential cellular response induced...... the laterodorsal tegmentum (LDT), a nucleus importantly involved in drug addiction associated behaviours, across two periods of ontogeny in which nicotine-mediated excitatory responses were shown to depend on age. To this end, whole-cell patch-clamp recordings in mouse brain slices from identified LDT neurons...

  20. Knockouts reveal overlapping functions of M2 and M4 muscarinic receptors and evidence for a local glutamatergic circuit within the laterodorsal tegmental nucleus

    Science.gov (United States)

    Kohlmeier, Kristi A.; Ishibashi, Masaru; Wess, Jürgen; Bickford, Martha E.

    2012-01-01

    Cholinergic neurons in the laterodorsal tegmental (LDT) and peduncolopontine tegmental (PPT) nuclei regulate reward, arousal, and sensory gating via major projections to midbrain dopamine regions, the thalamus, and pontine targets. Muscarinic acetylcholine receptors (mAChRs) on LDT neurons produce a membrane hyperpolarization and inhibit spike-evoked Ca2+ transients. Pharmacological studies suggest M2 mAChRs are involved, but the role of these and other localized mAChRs (M1--M4) has not been definitively tested. To identify the underlying receptors and to circumvent the limited receptor selectivity of available mAChR ligands, we used light- and electron-immunomicroscopy and whole cell recording with Ca2+ imaging in brain slices from knockout mice constitutively lacking either M2, M4, or both mAChRs. Immunomicroscopy findings support a role for M2 mAChRs, since cholinergic and noncholinergic LDT and pedunculopontine tegmental neurons contain M2-specific immunoreactivity. However, whole cell recording revealed that the presence of either M2 or M4 mAChRs was sufficient, and that the presence of at least one of these receptors was required for these carbachol actions. Moreover, in the absence of M2 and M4 mAChRs, carbachol elicited both direct excitation and barrages of spontaneous excitatory postsynaptic potentials (sEPSPs) in cholinergic LDT neurons mediated by M1 and/or M3 mAChRs. Focal carbachol application to surgically reduced slices suggest that local glutamatergic neurons are a source of these sEPSPs. Finally, neither direct nor indirect excitation were knockout artifacts, since each was detected in wild-type slices, although sEPSP barrages were delayed, suggesting M2 and M4 receptors normally delay excitation of glutamatergic inputs. Collectively, our findings indicate that multiple mAChRs coordinate cholinergic outflow from the LDT in an unexpectedly complex manner. An intriguing possibility is that a local circuit transforms LDT muscarinic inputs from a

  1. Anandamide and 2-AG Are Endogenously Present within the Laterodorsal Tegmental Nucleus: Functional Implications for a role of eCBs in arousal

    DEFF Research Database (Denmark)

    Soni, Neeraj; Prabhala, Bala Krishna; Mehta, Ved

    2017-01-01

    Previously, we presented electrophysiological evidence for presence in mice brain slices of functional cannabinoid type I receptors (CB1Rs) within the laterodorsal tegmentum (LDT), a brain stem nucleus critical in control of arousal and rapid eye movement (REM) sleep. Further, using pharmacological...... electrophysiological findings, lead to the suggestion that AEA and 2-AG act at electropharmacologically-demonstrated CB1Rs in this nucleus. Accordingly, AEA and 2-AG likely play a role in processes governed by the LDT, including control of states of cortical gamma band activity seen in alert, aroused states, as well...

  2. Functional interaction between OX2 and CB1 receptors in the ventral tegmental area and the nucleus accumbens in response to place preference induced by chemical stimulation of the lateral hypothalamus.

    Science.gov (United States)

    Yazdi, Fatemeh; Jahangirvand, Mahboubeh; Pirasteh, Amir-Hossein; Moradi, Marzieh; Haghparast, Abbas

    2015-12-01

    Orexinergic projections derived from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) and the nucleus accumbens (NAc), play a key role in the acquisition of conditioned place preference (CPP) induced by LH stimulation. On the other hand, there are several studies which support the idea of the existence of a cross-talk between the orexinergic and cannabinoid systems. Nevertheless, the function and how both systems interact in the reward circuit remain unknown. In this study, the authors tried to clarify the role of orexin-2 receptor (OX2r) within the VTA and NAc in the development of reward-related behaviors after chemical stimulation of the LH and also find out the involvement of CB1 cannabinoid receptors in this phenomenon. Animals were implanted by two separate cannulae into the LH and VTA or NAc, unilaterally. The CPP paradigm was done; and conditioning scores were recorded. The results showed that administration of TCS OX2 29 as a selective OX2r antagonist (1, 3 and 10 nM/rat) into the VTA or NAc just 5 min before microinjection of carbachol (250 nM/0.5 μl saline), a cholinergic agonist, into the LH during the 3-day conditioning phase, could dose-dependently inhibit the development of LH stimulation-induced CPP. Furthermore, concurrent injection of ineffective doses of TCS OX2 29 and AM251, as a CB1 receptor antagonist, into the NAc could reduce conditioning scores. The findings of this study showed that the OX2 receptor has a critical role in modulating reward circuit in the VTA and NAc, when the LH was stimulated by carbachol. Moreover, we suggest the existence of an interaction between orexinergic and cannabinoid systems within the VTA and NAc in place preference induced by LH stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Optogenetic Activation of the Sublaterodorsal (SLD) Nucleus Induces Rapid Muscle Inhibition

    Science.gov (United States)

    2015-09-01

    and neural activity, as measured with electroencephalography ( EEG ). One of the hallmarks of rapid eye movement (REM) sleep is muscle inhibition and is...than the prior studies previously cited that relied on pharmaceuticals to induce REM sleep . Building on this known literature, we have generated pilot... sleep /wake component we may need to alter our experimental paradigm and test whether we can influence EEG activity after the animal is already in SWS

  4. Nicotinic activation of laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

    2009-01-01

    ). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... depolarization that often induced firing and TTX-resistant inward currents. Nicotine also enhanced sensitivity to injected current; and, baseline changes in intracellular calcium were elicited in the dendrites of some cholinergic LDT cells. In addition, activity-dependent calcium transients were increased......, suggesting that nicotine exposure sufficient to induce firing may lead to enhancement of levels of intracellular calcium. Nicotine also had strong actions on glutamate and GABA-releasing presynaptic terminals, as it greatly increased the frequency of miniature EPSCs and IPSCs to both cholinergic and non...

  5. A magnetic resonance imaging finding in children with cerebral palsy: Symmetrical central tegmental tract hyperintensity.

    Science.gov (United States)

    Derinkuyu, Betul Emine; Ozmen, Evrim; Akmaz-Unlu, Havva; Altinbas, Namik Kemal; Gurkas, Esra; Boyunaga, Oznur

    2017-03-01

    Central tegmental tract is an extrapyramidal tract between red nucleus and inferior olivary nucleus which is located in the tegmentum pontis bilaterally and symmetrically. The etiology of the presence of central tegmental tract hyperintensity on MRI is unclear. In this study our aim is to evaluate the frequency of central tegmental tract lesions in patients with cerebral palsy and control group, as well as to determine whether there is an association between central tegmental tract lesions and cerebral palsy types. Clinical and MRI data of 200 patients with cerebral palsy in study group (87 female, 113 male; mean age, 5.81years; range, 0-16years) and 258 patients in control group (114 female, 144 male; mean age, 6.28years; range, 0-16years) were independently evaluated by two reader for presence of central tegmental tract hyperintensity and other associated abnormalities. Central tegmental tract hyperintensities on T2WI were detected in 19% of the study group (38/200) and 3.5% of the control group (9/258) (pcerebral palsy and 35% (14/40) in dyskinetic cerebral palsy (p=0.0131). The prevalence of central tegmental tract hyperintensity is higher in patients with cerebral palsy particularly in dyskinetic type. We suggest that there is an increased association of the tegmental lesions with dyskinetic CP. Patients with cerebral palsy and ischemic changes were more likely to have central tegmental tract lesions. According to our results we advocate that an ischemic process may have a role in the etiopathogenesis. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  6. Acute Cocaine Exposure elicits rises in calcium in Arousal Related Laterodorsal Tegmental Neurons

    DEFF Research Database (Denmark)

    Lambert, Mads; Ipsen, Theis; Kohlmeier, Kristi Anne

    2017-01-01

    Cocaine has strong reinforcing properties, which underlie its high addiction potential. Reinforcement of use of addictive drugs is associated with rises in dopamine (DA) in mesoaccumbal circuitry. Excitatory afferent input to mesoaccumbal circuitry sources from the laterodorsal tegmental nucleus ...... the role of intracellular calcium in cellular excitability, and of the LDT in addiction circuitry, our data suggest that cocaine effects in this nucleus may contribute to the high addiction potential of this drug.......Cocaine has strong reinforcing properties, which underlie its high addiction potential. Reinforcement of use of addictive drugs is associated with rises in dopamine (DA) in mesoaccumbal circuitry. Excitatory afferent input to mesoaccumbal circuitry sources from the laterodorsal tegmental nucleus...... (LDT). Chronic, systemic cocaine exposure has been shown to have cellular effects on LDT cells, but acute actions of local application have never been demonstrated. Using calcium imaging, we show that acute application of cocaine to mouse brain slices induces calcium spiking in cells of the LDT...

  7. Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area

    Directory of Open Access Journals (Sweden)

    Lauren Faget

    2016-06-01

    Full Text Available The ventral tegmental area (VTA plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity in neurotransmitter type, containing also GABA and glutamate neurons. Here, we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed, with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types, this study sheds important light on the systems-level organization of diverse inputs to VTA.

  8. Timing and expectation of reward: a neuro-computational model of the afferents to the ventral tegmental area

    Directory of Open Access Journals (Sweden)

    Julien eVitay

    2014-01-01

    Full Text Available Neural activity in dopaminergic areas such as the ventral tegmental area is influenced by timing processes, in particular by the temporal expectation of rewards during Pavlovian conditioning. Receipt of a reward at the expected time allows to compute reward-prediction errors which can drive learning in motor or cognitive structures. Reciprocally, dopamine plays an important role in the timing of external events. Several models of the dopaminergic system exist, but the substrate of temporal learning is rather unclear. In this article, we propose a neuro-computational model of the afferent network to the ventral tegmental area, including the lateral hypothalamus, the pedunculopontine nucleus, the amygdala, the ventromedial prefrontal cortex, the ventral basal ganglia (including the nucleus accumbens and the ventral pallidum, as well as the lateral habenula and the rostromedial tegmental nucleus. Based on a plausible connectivity and realistic learning rules, this neuro-computational model reproduces several experimental observations, such as the progressive cancellation of dopaminergic bursts at reward delivery, the appearance of bursts at the onset of reward-predicting cues or the influence of reward magnitude on activity in the amygdala and ventral tegmental area. While associative learning occurs primarily in the amygdala, learning of the temporal relationship between the cue and the associated reward is implemented as a dopamine-modulated coincidence detection mechanism in the nucleus accumbens.

  9. Endogenous Opioid-Induced Neuroplasticity of Dopaminergic Neurons in the Ventral Tegmental Area Influences Natural and Opiate Reward

    NARCIS (Netherlands)

    Pitchers, Kyle K.; Coppens, Caroline M.; Beloate, Lauren N.; Fuller, Jonathan; Van, Sandy; Frohmader, Karla S.; Laviolette, Steven R.; Lehman, Michael N.; Coolen, Lique M.

    2014-01-01

    Natural reward and drugs of abuse converge on the mesolimbic pathway and activate common mechanism of neural plasticity in the nucleus accumbens. Chronic exposure to opiates induces plasticity in dopaminergic neurons of the ventral tegmental area (VTA), which regulates morphine reward tolerance.

  10. Cognitive Neurostimulation: Learning to Volitionally Sustain Ventral Tegmental Area Activation

    Science.gov (United States)

    MacInnes, Jeff J.; Dickerson, Kathryn C.; Chen, Nan-kuei; Adcock, R. Alison

    2016-01-01

    SUMMARY Activation of the ventral tegmental area (VTA) and mesolimbic networks is essential to motivation, performance, and learning. Humans routinely attempt to motivate themselves, with unclear efficacy or impact on VTA networks. Using fMRI, we found untrained participants’ motivational strategies failed to consistently activate VTA. After real-time VTA neurofeedback training, however, participants volitionally induced VTA activation without external aids, relative to baseline, Pre-Test, and control groups. VTA self-activation was accompanied by increased mesolimbic network connectivity. Among two comparison groups (no neurofeedback, false neurofeedback) and an alternate neurofeedback group (nucleus accumbens), none sustained activation in target regions of interest nor increased VTA functional connectivity. The results comprise two novel demonstrations: learning and generalization after VTA neurofeedback training and the ability to sustain VTA activation without external reward or reward cues. These findings suggest theoretical alignment of ideas about motivation and midbrain physiology and the potential for generalizable interventions to improve performance and learning. PMID:26948894

  11. Concomitant release of ventral tegmental acetylcholine and accumbal dopamine by ghrelin in rats.

    Directory of Open Access Journals (Sweden)

    Elisabet Jerlhag

    Full Text Available Ghrelin, an orexigenic peptide, regulates energy balance specifically via hypothalamic circuits. Growing evidence suggest that ghrelin increases the incentive value of motivated behaviours via activation of the cholinergic-dopaminergic reward link. It encompasses the cholinergic afferent projection from the laterodorsal tegmental area (LDTg to the dopaminergic cells of the ventral tegmental area (VTA and the mesolimbic dopamine system projecting from the VTA to nucleus accumbens (N.Acc.. Ghrelin receptors (GHS-R1A are expressed in these reward nodes and ghrelin administration into the LDTg increases accumbal dopamine, an effect involving nicotinic acetylcholine receptors in the VTA. The present series of experiments were undertaken directly to test this hypothesis. Here we show that ghrelin, administered peripherally or locally into the LDTg concomitantly increases ventral tegmental acetylcholine as well as accumbal dopamine release. A GHS-R1A antagonist blocks this synchronous neurotransmitter release induced by peripheral ghrelin. In addition, local perfusion of the unselective nicotinic antagonist mecamylamine into the VTA blocks the ability of ghrelin (administered into the LDTg to increase N.Acc.-dopamine, but not VTA-acetylcholine. Collectively our data indicate that ghrelin activates the LDTg causing a release of acetylcholine in the VTA, which in turn activates local nicotinic acetylcholine receptors causing a release of accumbal dopamine. Given that a dysfunction in the cholinergic-dopaminergic reward system is involved in addictive behaviours, including compulsive overeating and alcohol use disorder, and that hyperghrelinemia is associated with such addictive behaviours, ghrelin-responsive circuits may serve as a novel pharmacological target for treatment of alcohol use disorder as well as binge eating.

  12. Ventral tegmental area dopamine revisited: effects of acute and repeated stress

    Science.gov (United States)

    Holly, Elizabeth N.; Miczek, Klaus A.

    2015-01-01

    Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression. PMID:26676983

  13. Lesions of the fasciculus retroflexus alter footshock-induced cFos expression in the mesopontine rostromedial tegmental area of rats.

    Directory of Open Access Journals (Sweden)

    Paul Leon Brown

    Full Text Available Midbrain dopamine neurons are an essential part of the circuitry underlying motivation and reinforcement. They are activated by rewards or reward-predicting cues and inhibited by reward omission. The lateral habenula (lHb, an epithalamic structure that forms reciprocal connections with midbrain dopamine neurons, shows the opposite response being activated by reward omission or aversive stimuli and inhibited by reward-predicting cues. It has been hypothesized that habenular input to midbrain dopamine neurons is conveyed via a feedforward inhibitory pathway involving the GABAergic mesopontine rostromedial tegmental area. Here, we show that exposing rats to low-intensity footshock (four, 0.5 mA shocks over 20 min induces cFos expression in the rostromedial tegmental area and that this effect is prevented by lesions of the fasciculus retroflexus, the principal output pathway of the habenula. cFos expression is also observed in the medial portion of the lateral habenula, an area that receives dense DA innervation via the fr and the paraventricular nucleus of the thalamus, a stress sensitive area that also receives dopaminergic input. High-intensity footshock (120, 0.8 mA shocks over 40 min also elevates cFos expression in the rostromedial tegmental area, medial and lateral aspects of the lateral habenula and the paraventricular thalamus. In contrast to low-intensity footshock, increases in cFos expression within the rostromedial tegmental area are not altered by fr lesions suggesting a role for non-habenular inputs during exposure to highly aversive stimuli. These data confirm the involvement of the lateral habenula in modulating the activity of rostromedial tegmental area neurons in response to mild aversive stimuli and suggest that dopamine input may contribute to footshock- induced activation of cFos expression in the lateral habenula.

  14. Direct effect of nicotine on mesolimbic dopamine release in rat nucleus accumbens shell

    NARCIS (Netherlands)

    Kleijn, J.; Folgering, J. H. A.; van der Hart, M. C. G.; Rollema, H.; Cremers, T. I. F. H.; Westerink, B. H. C.

    2011-01-01

    Nicotine stimulates dopamine (DA) cell firing via a local action at somatodendritic sites in the ventral tegmental area (VTA), increasing DA release in the nucleus accumbens (NAcc). Additionally, nicotine may also modulate DA release via a direct effect in the NAcc. This study examined the

  15. Ventral Tegmental Area Afferents and Drug-Dependent Behaviors

    OpenAIRE

    Idaira eOliva; Matthew eWanat

    2016-01-01

    Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA), a midbrain structure comprised of dopamine, GABA, and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects o...

  16. Gudden's Ventral Tegmental Nucleus Is Vital for Memory: Re-Evaluating Diencephalic Inputs for Amnesia

    Science.gov (United States)

    Vann, Seralynne D.

    2009-01-01

    Mammillary body atrophy is present in a number of neurological conditions and recent clinical findings highlight the importance of these nuclei for memory. While most accounts of diencephalic amnesia emphasize the functional importance of the hippocampal projections to the mammillary bodies, the present study tested the importance of the other…

  17. Modification of behavioral responses induced by electrical stimulation of the ventral tegmental area in rats.

    Science.gov (United States)

    Watanabe, T; Morimoto, K; Nakamura, M; Suwaki, H

    1998-06-01

    To investigate the role of the ventral tegmental area (VTA), a source of the mesolimbic dopaminergic pathway, in paranoid psychosis, a detailed analysis of the behavioral responses induced by electrical stimulation of the VTA was made. Abnormal behavior induced by bilateral high-frequency stimulation of the VTA consisted of two components: forward locomotion and exploration. Similar responses were obtained when the nucleus accumbens (NAC) or prefrontal cortex (PFC) were stimulated. The expression of behavioral responses to stimulation was significantly attenuated by dopamine (DA) receptor or antagonists, such as haloperidol, YM-09151-2 and SCH23390. These results indicate that VTA stimulation causes a transient hyperdopaminergic state in the brain, that resembles psychostimulant-induced abnormal behavior. The effects of chronic administration of methamphetamine (MAP) on the behavioral responses to electrical stimulation of the VAT were also investigated. Although an acute administration of MAP did not affect the behavioral responses to electrical stimulation of the VTA, chronic treatment with MAP (for 2 weeks) caused a long-lasting reduction in the electrical threshold for the induction of abnormal behavior, compared with chronic saline-treated rats. It is suggested that a lasting enhancement in the behavioral response to stimulation of VTA neurons may contribute to the etiology of paranoid schizophrenia and amphetamine psychosis.

  18. Symmetrical central tegmental tract (CTT) hyperintense lesions on magnetic resonance imaging in children

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Shoko; Hayakawa, Katsumi; Yamamoto, Akira [Kyoto City Hospital, Department of Radiology, Kyoto (Japan); Aida, Noriko [Kanagawa Children' s Medical Center, Department of Radiology, Kyoto (Japan); Okano, Souzo; Matsushita, Hiroko [Kyoto City Hospital, Department of Pediatrics, Kyoto (Japan); Kanda, Toyoko; Yamori, Yuriko; Yoshida, Naoko; Hirota, Haruyo [St. Joseph Hospital for Handicapped Children, Department of Pediatric Neurology, Kyoto (Japan)

    2009-02-15

    The central tegmental tract (CTT) is mainly the extrapyramidal tract connecting between the red nucleus and the inferior olivary nucleus. There are only a few case reports describing CTT abnormalities on magnetic resonance imaging (MRI) in children. Our purpose was to evaluate the frequency of CTT lesions and their characteristics on MRI, and to correlate the MR imaging findings with clinical features. We reviewed retrospectively the MR images of 392 children (215 boys and 177 girls) ranging in age from 1 to 6 years. To evaluate symmetrical CTT hyperintense lesions, we defined a CTT lesion as an area of bilateral symmetrical hyperintensity in the tegmentum pontis on both T2-weighted images and diffusion-weighted images in more than two slices. We measured the ADC (apparent diffusion coefficient) values of symmetrical CTT hyperintensity, and compared them with those of children without CTT abnormality. CTT lesions were detected in 20 (5.1%) of the 392 children. The mean ADC value for these 20 children was significantly lower than that of the normal CTT (p<0.001). On MR imaging, other than CTT lesions, associated parenchymal lesion included: none (n=6); other abnormalities, including periventricular leukomalacia (n=3); thin corpus callosum (n=3); ventricular dilatation (n=2); encephalopathy (n=2). Clinically, cerebral palsy was the most frequent clinical diagnosis (n=6), accounting for 30%, which was significantly more frequent than the prevalence of cerebral palsy among children without CTT lesions (13%) (n<0.05). CTT lesions were detected in 5.1% of all the children examined. Cerebral palsy was the most frequent clinical diagnosis. (orig.)

  19. Cholinergic and non-cholinergic projections from the pedunculopontine and laterodorsal tegmental nuclei to the medial geniculate body in guinea pigs

    Directory of Open Access Journals (Sweden)

    Susan D Motts

    2010-10-01

    Full Text Available The midbrain tegmentum is the source of cholinergic innervation of the thalamus and has been associated with arousal and control of the sleep/wake cycle. In general, the innervation arises bilaterally from the pedunculopontine tegmental nucleus (PPT and the laterodorsal tegmental nucleus (LDT. While this pattern has been observed for many thalamic nuclei, a projection from the LDT to the medial geniculate body (MG has been questioned in some species. We combined retrograde tracing with immunohistochemistry for choline acetyltransferase (ChAT to identify cholinergic projections from the brainstem to the MG in guinea pigs. Double-labeled cells (retrograde and immunoreactive for ChAT were found in both the PPT (74% and the LDT (26%. In both nuclei, double-labeled cells were more numerous on the ipsilateral side. About half of the retrogradely labeled cells were immunonegative, suggesting they are non-cholinergic. The distribution of these immunonegative cells was similar to that of the immunopositive ones: more were in the PPT than the LDT and more were on the ipsilateral than the contralateral side. The results indicate that both the PPT and the LDT project to the MG, and suggest that both cholinergic and non-cholinergic cells contribute substantially to these projections.

  20. The Appetite-Inducing Peptide, Ghrelin, Induces Intracellular Store-Mediated Rises in Calcium in Addiction and Arousal-Related Laterodorsal Tegmental Neurons in Mouse Brain Slices

    DEFF Research Database (Denmark)

    Hauberg, Katrine; Kohlmeier, Kristi Anne

    2015-01-01

    Ghrelin, a gut and brain peptide, has recently been shown to be involved in motivated behavior and regulation of the sleep and wakefulness cycle. The laterodorsal tegmental nucleus (LDT) is involved in appetitive behavior and control of the arousal state of an organism, and accordingly, behavioral...... actions of ghrelin could be mediated by direct cellular actions within this nucleus. Consistent with this interpretation, postsynaptically mediated depolarizing membrane actions of ghrelin on LDT neurons have been reported. Direct actions were ascribed solely to closure of a potassium conductance however...... this peptide has been shown in other cell types to lead to rises in calcium via release of calcium from intracellular stores. To determine whether ghrelin induced intracellular calcium rises in mouse LDT neurons, we conducted calcium imaging studies in LDT brain slices loaded with the calcium binding dye, Fura...

  1. GABAA receptor drugs and neuronal plasticity in reward and aversion: focus on the ventral tegmental area

    Directory of Open Access Journals (Sweden)

    Elena eVashchinkina

    2014-11-01

    Full Text Available GABAA receptors are the main fast inhibitory neurotransmitter receptors in the mammalian brain, and targets for many clinically important drugs widely used in the treatment of anxiety disorders, insomnia and in anesthesia. Nonetheless, there are significant risks associated with the long-term use of these drugs particularly related to development of tolerance and addiction. Addictive mechanisms of GABAA receptor drugs are poorly known, but recent findings suggest that those drugs may induce aberrant neuroadaptations in the brain reward circuitry. Recently, benzodiazepines, acting on synaptic GABAA receptors, and modulators of extrasynaptic GABAA receptors (THIP and neurosteroids have been found to induce plasticity in the ventral tegmental area (VTA dopamine neurons and their main target projections. Furthermore, depending whether synaptic or extrasynaptic GABAA receptor populations are activated, the behavioral outcome of repeated administration seems to correlate with rewarding or aversive behavioral responses, respectively. The VTA dopamine neurons project to forebrain centers such as the nucleus accumbens and medial prefrontal cortex, and receive afferent projections from these brain regions and especially from the extended amygdala and lateral habenula, forming the major part of the reward and aversion circuitry. Both synaptic and extrasynaptic GABAA drugs inhibit the VTA GABAergic interneurons, thus activating the VTA DA neurons by disinhibition and this way inducing glutamatergic synaptic plasticity. However, the GABAA drugs failed to alter synaptic spine numbers as studied from Golgi-Cox-stained VTA dendrites. Since the GABAergic drugs are known to depress the brain metabolism and gene expression, their likely way of inducing neuroplasticity in mature neurons is by disinhibiting the principal neurons, which remains to be rigorously tested for a number of clinically important anxiolytics, sedatives and anesthetics in different parts of

  2. Reduced Ventral Tegmental Area-Hippocampal Connectivity in Children and Adolescents Exposed to Early Threat.

    Science.gov (United States)

    Marusak, Hilary A; Hatfield, Joshua R B; Thomason, Moriah E; Rabinak, Christine A

    2017-03-01

    Preclinical data suggest that early life stress has detrimental effects on the brain's dopaminergic system, particularly the mesocorticolimbic pathway. Altered dopamine function is thought to contribute to the development of stress-related pathologies; yet, little is known about the impact of early stress on dopamine systems during childhood and adolescence, when stress-related disorders frequently emerge. Here, we evaluate the impact of early threat exposure (violence, abuse) on functional connectivity of putative dopaminergic midbrain regions, the ventral tegmental area (VTA) and substantia nigra (SN), giving rise to mesocorticolimbic and nigrostriatal pathways, respectively. Resting-state functional magnetic resonance imaging scans were completed in 43 trauma-exposed and 43 matched comparison youth (ages 7-17). Functional connectivity of the VTA and SN were compared between groups. The trauma group demonstrated lower functional connectivity between the VTA and hippocampus. No group differences in SN connectivity were observed. Across all participants, there were age-related decreases in connectivity of both VTA and SN with the hippocampus, suggesting that age-related attenuations in VTA-hippocampal circuitry may be exacerbated in trauma-exposed youth. Higher levels of anxiety symptomology were associated with reduced SN-nucleus accumbens connectivity. Prior research suggests that VTA-hippocampal circuitry is critical for the gating of new information into long-term memory. Lower connectivity in this circuitry suggests a novel mechanism that may serve to adaptively prevent the overwriting of a previously stored trauma memory, but at the same time contribute to the broad range of cognitive and emotional difficulties linked to early stress exposure.

  3. Alpha-melanocyte stimulating hormone modulates ethanol self-administration in posterior ventral tegmental area through melanocortin-4 receptors.

    Science.gov (United States)

    Shelkar, Gajanan P; Kale, Atmaram D; Singh, Uday; Singru, Praful S; Subhedar, Nishikant K; Kokare, Dadasaheb M

    2015-03-01

    Although the role of alpha-melanocyte stimulating hormone (α-MSH) in alcohol seeking behaviour in rats has been demonstrated, the underlying mechanisms are not understood. Herein, we test the hypothesis that α-MSH might have a permissive effect in promoting the reward action of ethanol. Rats were implanted with cannulae targeted at the posterior ventral tegmental area (pVTA), because the site is sensitive to reinforcing effects of ethanol. These rats were trained to self-administer ethanol in standard two-lever (active/inactive) operant chamber test. Each active lever press resulted in self-administration of 100 nl of ethanol (100-300 mg%) containing solution. Over a period of 7 days, ethanol significantly increased the number of lever presses, which was considered as a measure of reward. Because ethanol at 200 mg% resulted in maximum number of lever presses (∼18-20 lever presses/30-minute session), the dose was employed in further studies. While prior administration of melanocortin (MC) agonists, α-MSH or [Nle4,D-Phe7]-alpha-MSH into pVTA, resulted in an 89% increase in lever presses, the response was attenuated following pre-treatment with MC4 receptors (MC4R) antagonist, HS014. In an immunohistochemical study, the brains of rats that were trained to self-infuse ethanol showed significantly increased α-MSH immunoreactivity in the nucleus accumbens shell, bed nucleus of stria terminalis and arcuate nucleus of the hypothalamus. In the pVTA, α-MSH fibres were found to run close to the dopamine cells, labelled with tyrosine hydroxylase antibodies. We suggest that α-MSH-MC4R system in the pVTA might be a part of the neuroadaptive mechanism underlying ethanol addiction. © 2014 Society for the Study of Addiction.

  4. Ventral tegmental area afferents and drug-dependent behaviors

    Directory of Open Access Journals (Sweden)

    Idaira eOliva

    2016-03-01

    Full Text Available Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA, a midbrain structure comprised of dopamine, GABA and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects of drugs. In this review we present evidence implicating the VTA in drug-related behaviors, highlight the diversity of neuronal populations in the VTA, and discuss the behavioral effects of selectively manipulating VTA afferents. Future experiments are needed to determine which VTA afferents and what neuronal populations in the VTA mediate specific drug-dependent behaviors. Further studies are also necessary for identifying the afferent-specific synaptic alterations onto dopamine and non-dopamine neurons in the VTA following drug administration. The identification of neural circuits and adaptations involved with drug-dependent behaviors can highlight potential neural targets for pharmacological and deep brain stimulation interventions to treat substance abuse disorders.

  5. Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

    DEFF Research Database (Denmark)

    Christensen, Mark Holm; Ishibashi, Masaru; Nielsen, Michael Linnemann

    2014-01-01

    The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved...... in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7–P15), nicotine induced larger...... intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15–P34). Nicotine increased neuronal firing of cholinergic cells...

  6. Identification of Rat Ventral Tegmental Area GABAergic Neurons

    Science.gov (United States)

    Margolis, Elyssa B.; Toy, Brian; Himmels, Patricia; Morales, Marisela; Fields, Howard L.

    2012-01-01

    The canonical two neuron model of opioid reward posits that mu opioid receptor (MOR) activation produces reward by disinhibiting midbrain ventral tegmental area (VTA) dopamine neurons through inhibition of local GABAergic interneurons. Although indirect evidence supports the neural circuit postulated by this model, its validity has been called into question by growing evidence for VTA neuronal heterogeneity and the recent demonstration that MOR agonists inhibit GABAergic terminals in the VTA arising from extrinsic neurons. In addition, VTA MOR reward can be dopamine-independent. To directly test the assumption that MOR activation directly inhibits local GABAergic neurons, we investigated the properties of rat VTA GABA neurons directly identified with either immunocytochemistry for GABA or GAD65/67, or in situ hybridization for GAD65/67 mRNA. Utilizing co-labeling with an antibody for the neural marker NeuN and in situ hybridization against GAD65/67, we found that 23±3% of VTA neurons are GAD65/67(+). In contrast to the assumptions of the two neuron model, VTA GABAergic neurons are heterogeneous, both physiologically and pharmacologically. Importantly, only 7/13 confirmed VTA GABA neurons were inhibited by the MOR selective agonist DAMGO. Interestingly, all confirmed VTA GABA neurons were insensitive to the GABAB receptor agonist baclofen (0/6 inhibited), while all confirmed dopamine neurons were inhibited (19/19). The heterogeneity of opioid responses we found in VTA GABAergic neurons, and the fact that GABA terminals arising from neurons outside the VTA are inhibited by MOR agonists, make further studies essential to determine the local circuit mechanisms underlying VTA MOR reward. PMID:22860119

  7. Local field potentials in the ventral tegmental area during cocaine-induced locomotor activation: Measurements in freely moving rats.

    Science.gov (United States)

    Harris Bozer, Amber L; Li, Ai-Ling; Sibi, Jiny E; Bobzean, Samara A M; Peng, Yuan B; Perrotti, Linda I

    2016-03-01

    The ventral tegmental area (VTA) has been established as a critical nucleus for processing behavioral changes that occur during psychostimulant use. Although it is known that cocaine induced locomotor activity is initiated in the VTA, not much is known about the electrical activity in real time. The use of our custom-designed wireless module for recording local field potential (LFP) activity provides an opportunity to confirm and identify changes in neuronal activity within the VTA of freely moving rats. The purpose of this study was to investigate the changes in VTA LFP activity in real time that underlie cocaine induced changes in locomotor behavior. Recording electrodes were implanted in the VTA of rats. Locomotor behavior and LFP activity were simultaneously recorded at baseline, and after saline and cocaine injections. Results indicate that cocaine treatment caused increases in both locomotor behavior and LFP activity in the VTA. Specifically, LFP activity was highest during the first 30 min following the cocaine injection and was most robust in Delta and Theta frequency bands; indicating the role of low frequency VTA activity in the initiation of acute stimulant-induced locomotor behavior. Our results suggest that LFP recording in freely moving animals can be used in the future to provide valuable information pertaining to drug induced changes in neural activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Role of the medullary lateral tegmental field in sympathetic control.

    Science.gov (United States)

    Ghali, Michael George Zaki

    2017-01-01

    The sympathetic nervous system maintains and regulates arterial pressure and tissue perfusion, via control of cardiac output and vasomotor tone. Sympatho-vascular-mediated increases in blood pressure are effected by arterioloconstriction, which causes an increase in afterload, and/or venoconstriction, which increases venous return, left ventricular preload, and consequently, the force of cardiac contraction via Frank-Starling mechanisms; withdrawal of sympathetic drive elicits reciprocal effects. Spinalization reduces mammalian arterial pressure to 40-50 mm Hg consequent to the elimination of descending medullary pre-sympathetic bulbospinal drive to preganglionic sympathetic fibers in the intermediolateral cell column of the spinal cord. Beyond agreement that sympathetic tone is generated supraspinally, there is only controversy. One hypothesis posits that pre-sympathetic medullary regions, such as the rostral ventrolateral medulla (RVLM) and caudal raphé group, possess intrinsic tonic activity. Alternatively, pre-sympathetic medullary regions may receive tonic excitation from other areas in the brainstem. Neurons in the lateral tegmental field (LTF), an exclusively propriobulbar entity (cf. pre-Bötzinger complex - the propriobulbar inspiratory rhythmogenic kernel of the respiratory network), fire before and project to pre-sympathetic units in RVLM and caudal raphé and exhibit activity correlated to the cardiac-related rhythm in sympathetic nerve discharge, making the LTF a likely candidate for the primary source of basal sympathoexcitation. The LTF is additionally involved in a variety of cardiovascular and sympathetic reflexes (i.e., baroreflex, Bezold-Jarisch reflex). As it receives descending afferents from the infralimbic cortex and associated limbic structures, suggesting a role in the sympathetic response to fear, as well as vestibular inputs, consistent with a role in coordinating the sympathetic response with emesis proper, the LTF appears to play an

  9. Multifractal analysis of nucleus-nucleus interactions

    Energy Technology Data Exchange (ETDEWEB)

    Sengupta, K.; Cherry, M.L.; Jones, W.V.; Wefel, J.P. (Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803 (United States)); Dabrowska, A.; Holynski, R.; Jurak, A.; Olszewski, A.; Szarska, M.; Trzupek, A.; Wilczynska, B.; Wilczynski, H.; Wolter, W.; Wosiek, B.; Wozniak, K. (Institute of Nuclear Physics, Kawiory 26 A, 30-055, Krakow (Poland)); Freier, P.S.; Waddington, C.J. (School of Physics and Astronomy, University of Minnesota, Minneapolis, Minnesota 55455 (United States)); (KLM Collaboration)

    1993-10-01

    We have performed a multifractal ([ital G]-moment) analysis of 14.6--200 GeV/nucleon nucleus-nucleus and 200--800 GeV proton-nucleus interactions from KLM and Fermilab E-90 and E-508 emulsion data, including explicit corrections for the finite statistical sample. The corrected slopes of the [ital G] moments for protons, [sup 16]O, [sup 28]Si, and [sup 32]S nuclei show only slight evidence for departures from random behavior, while the normalized entropies appear to show a more consistent departure from randomness, particularly for protons. Given the size of the uncertainties, the results of the fractal analysis are not consistent either with results of intermittency analyses for nucleus-nucleus collisions or with the nonrandom behavior previously reported for leptonic and hadronic collisions. However, because of the effects of statistical noise, the fractal analysis is not as sensitive as the intermittency analysis for detecting nonrandom fluctuations.

  10. Role of the Ventral Tegmental Area in Methamphetamine Extinction: AMPA Receptor-Mediated Neuroplasticity

    Science.gov (United States)

    Chen Han-Ting; Chen, Jin-Chung

    2015-01-01

    The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned…

  11. Morphine withdrawal enhances constitutive μ-opioid receptor activity in the ventral tegmental area

    NARCIS (Netherlands)

    Meye, F.J.; van Zessen, R.; Smidt, M.P.; Adan, R.A.H.; Ramakers, G.M.J.

    2012-01-01

    μ-opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive

  12. Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation

    NARCIS (Netherlands)

    de Jong, Johannes W.; Roelofs, Theresia J M; Mol, Frédérique M U; Hillen, Anne E J; Meijboom, Katharina E.; Luijendijk, Mieneke C M; Van Der Eerden, Harrie A M; Garner, Keith M.; Vanderschuren, Louk J M J; Adan, Roger A H

    2015-01-01

    Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area

  13. Onuf's nucleus X

    DEFF Research Database (Denmark)

    Schrøder, H D

    1981-01-01

    The first, second and third sacral segments of 59 human spinal cords were examined in order to localize and describe Onuf's nucleus X. The nucleus was found to be situated in the ventral horn of the segments S2 and S3; only in very few spinal cords did it extend into S1. A significant variation...... in the length of the nucleus was observed. Based on the cytoarchitecture the nucleus could be divided in three parts, a cranial, a dorsomedial and a ventrolateral. All parts of the nucleus consisted of chromatin-rich medium-sized neurons, and apparent direct appositions between different cells bodies as well...... as between cell bodies and large dendrites were observed. Characteristic findings in the neuropil surrounding the nucleus were the sparsity of myelinated fibers and the presence of dendritic bundles. The present observations are compared to the descriptions of a morphologically similar nucleus...

  14. Differential role of ventral tegmental area acetylcholine and N-Methyl-D-Aspartate receptors in cocaine-seeking

    Science.gov (United States)

    Solecki, Wojciech; Wickham, Robert J.; Behrens, Shay; Wang, Jie; Zwerling, Blake; Mason, Graeme F.; Addy, Nii A.

    2013-01-01

    Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Cues evoke burst firing of ventral tegmental area (VTA) dopamine (DA) neurons and phasic DA release in the nucleus accumbens (NAc). Cholinergic and glutamatergic input to the VTA is suggested to gate phasic DA activity. However, the role of VTA cholinergic and glutamatergic receptors in regulating phasic dopamine release and cue-induced drug-seeking in cocaine experienced subjects is not known. In male Sprague-Dawley rats, we found that VTA inactivation strongly inhibited, while VTA stimulation promoted, cocaine-seeking behavior during early withdrawal. Blockade of phasic activated D1 receptors in the NAc core also strongly inhibited cue-induced cocaine-seeking - suggesting an important role of phasic DA activity in the VTA to NAc core circuit. Next, we examined the role of VTA acetylcholine receptors (AChRs) and N-methyl-D-aspartate receptors (NMDARs) in regulating both NAc core phasic DA release and cue-induced cocaine-seeking. In cocaine naïve subjects, VTA infusion of the nicotinic acetylcholine receptor (AChR) antagonist mecamylamine, the muscarinic AChR antagonist scopolamine, or the NMDAR antagonist AP-5, led to robust attenuation of phasic DA release in the NAc core. During early cocaine withdrawal, VTA infusion of AP-5 had limited effects on NAc phasic DA release and cue-induced cocaine-seeking while VTA infusion of mecamylamine or scopolamine robustly inhibited both phasic DA release and cocaine-seeking. The results demonstrate that VTA AChRs, but not NMDARs, strongly regulate cue-induced cocaine-seeking and phasic DA release during early cocaine withdrawal. PMID:23850572

  15. Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis

    Directory of Open Access Journals (Sweden)

    Ana eAransay

    2015-05-01

    Full Text Available Pathways arising from the ventral tegmental area (VTA release dopamine and other neurotransmitters during the expectation and achievement of reward, and are regarded as central links of the brain networks that create drive, pleasure, and addiction. While the global pattern of VTA projections is well-known, the actual axonal wiring of individual VTA neurons had never been investigated. Here, we labeled and analyzed the axons of 30 VTA single neurons by means of single-cell transfection with the Sindbis-pal-eGFP vector in mice. These observations were complemented with those obtained by labeling the axons of small populations of VTA cells with iotophoretic microdeposits of biotinylated dextran amine. In the single-cell labeling experiments, each entire axonal tree was reconstructed from serial sections, the length of terminal axonal arbors was estimated by stereology, and the dopaminergic phenotype was tested by double-labeling for tyrosine hydroxylase immunofluorescence. We observed two main, markedly different VTA cell morphologies: neurons with a single main axon targeting only forebrain structures (FPN cells, and neurons with multibranched axons targeting both the forebrain and the brainstem (F+BSPN cells. Dopaminergic phenotype was observed in FPN cells. Moreover, four subtypes could be distinguished among the FPN cells based on their projection targets: 1 Mesocorticolimbic FPN projecting to both neocortex and basal forebrain; 2 Mesocortical FPN innervating the neocortex almost exclusively; 3 Mesolimbic FPN projecting to the basal forebrain, accumbens and caudateputamen; and 4 Mesostriatal FPN targeting only the caudateputamen. While the F+BSPN cells were scattered within VTA, the mesolimbic neurons were abundant in the paranigral nucleus. The observed diversity in wiring architectures is consistent with the notion that different VTA cell subpopulations modulate the activity of specific sets of prosencephalic and brainstem structures.

  16. Nicotine self-administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats.

    Science.gov (United States)

    Vazquez-Sanroman, Dolores B; Monje, Reyna D; Bardo, Michael T

    2017-11-01

    Nicotine, a major psychoactive component of tobacco smoke, alters gamma-aminobutyric acid (GABA) modulation of dopamine neurons in the ventral tegmental area (VTA). Changes in structural neuroplasticity can occur in GABAergic parvalbumin (PRV) positive neurons, which are enveloped by structures of the extracellular matrix called perineuronal nets (PNNs). In the current study, rats were trained to self-administer intravenous nicotine (0.03 mg/kg/infusion) for 21 days in 1-hour daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions. At either 45 minutes or 72 hours after the last session, immunofluorescence measurements for PNNs, PRV and c-Fos were conducted. In VTA, nicotine self-administration reduced the number of PRV+ cells surrounded by PNNs at 45 minutes, as well as reducing the intensity of PNNs, suggesting a remodeling of GABA interneurons in this region; the number of PRV+ cells surrounded by PNNs was also reduced at 72 hours. A similar reduction of PNNs occurred in orbitofrontal cortex (OFC) but not in medial prefrontal cortex (prelimbic or infralimbic), 45 minutes after the last session; PNNs were not detected in nucleus accumbens (shell or core). The reduction of PNNs in VTA and OFC was unrelated to c-Fos + cells, as the percent of wisteria floribunda agglutinin + cells co-expressing c-Fos was decreased in OFC but not in VTA. Thus, nicotine self-administration remodeled PNNs surrounding GABA interneurons in VTA and its indirect connections to OFC, suggesting a new possible molecular target where nicotine-induced neuroplasticity takes place. PNN manipulations may prevent or reverse the different stages of tobacco addiction. © 2016 Society for the Study of Addiction.

  17. Cocaine-Induced Endocannabinoid Mobilization in the Ventral Tegmental Area

    Directory of Open Access Journals (Sweden)

    Huikun Wang

    2015-09-01

    Full Text Available Cocaine is a highly addictive drug that acts upon the brain’s reward circuitry via the inhibition of monoamine uptake. Endogenous cannabinoids (eCB are lipid molecules released from midbrain dopamine (DA neurons that modulate cocaine’s effects through poorly understood mechanisms. We find that cocaine stimulates release of the eCB, 2-arachidonoylglycerol (2-AG, in the rat ventral midbrain to suppress GABAergic inhibition of DA neurons, through activation of presynaptic cannabinoid CB1 receptors. Cocaine mobilizes 2-AG via inhibition of norepinephrine uptake and promotion of a cooperative interaction between Gq/11-coupled type-1 metabotropic glutamate and α1-adrenergic receptors to stimulate internal calcium stores and activate phospholipase C. The disinhibition of DA neurons by cocaine-mobilized 2-AG is also functionally relevant because it augments DA release in the nucleus accumbens in vivo. Our results identify a mechanism through which the eCB system can regulate the rewarding and addictive properties of cocaine.

  18. Astroglial MicroRNA-219-5p in the Ventral Tegmental Area Regulates Nociception in Rats.

    Science.gov (United States)

    Zhang, Song; Yang, Xiao-Na; Zang, Ting; Luo, Jun; Pan, Zhiqiang; Wang, Lei; Liu, He; Liu, Di; Li, Yan-Qiang; Zhang, Yao-Dong; Zhang, Hongxing; Ding, Hai-Lei; Cao, Jun-Li

    2017-09-01

    The authors previously reported that noncoding microRNA miR-219-5p is down-regulated in the spinal cord in a nociceptive state. The ventral tegmental area also plays critical roles in modulating nociception, although the underlying mechanism remains unknown. The authors hypothesized that miR-219-5p in the ventral tegmental area also may modulate nociception. The authors studied the bidirectional regulatory role of ventral tegmental area miR-219-5p in a rat complete Freund's adjuvant model of inflammatory nociception by measuring paw withdrawal latencies. Using molecular biology technologies, the authors measured the effects of astroglial coiled-coil and C2 domain containing 1A/nuclear factor κB cascade and dopamine neuron activity on the down-regulation of ventral tegmental area miR-219-5p-induced nociceptive responses. MiR-219-5p expression in the ventral tegmental area was reduced in rats with thermal hyperalgesia. Viral overexpression of ventral tegmental area miR-219-5p attenuated complete Freund's adjuvant-induced nociception from 7 days after complete Freund's adjuvant injection (paw withdrawal latencies: 6.09 ± 0.83 s vs. 3.96 ± 0.76 s; n = 6/group). Down-regulation of ventral tegmental area miR-219-5p in naïve rats was sufficient to induce thermal hyperalgesia from 7 days after lentivirus injection (paw withdrawal latencies: 7.09 ± 1.54 s vs. 11.75 ± 2.15 s; n = 8/group), which was accompanied by increased glial fibrillary acidic protein (fold change: 2.81 ± 0.38; n = 3/group) and reversed by intraventral tegmental area injection of the astroglial inhibitor fluorocitrate. The nociceptive responses induced by astroglial miR-219-5p down-regulation were inhibited by interfering with astroglial coiled-coil and C2 domain containing 1A/nuclear factor-κB signaling. Finally, pharmacologic inhibition of ventral tegmental area dopamine neurons alleviated this hyperalgesia. Down-regulation of astroglial miR-219-5p in ventral

  19. The human substantia nigra and ventral tegmental area. A neuroanatomical study with notes on aging and aging diseases.

    Science.gov (United States)

    van Domburg, P H; ten Donkelaar, H J

    1991-01-01

    The present study comprises a cytoarchitectonic analysis of the human substantia nigra (SN) and ventral tegmental area (VTA); a discussion of their chemoarchitecture and fiber connections (mainly based on tract-tracing studies in primates) preceded by an overview of the wealth of tract-tracing data in rodents; a discussion of the involvement of the SN/VTA complex in Parkinson's disease (PD) and related disorders and in Alzheimer's disease (AD), including some quantitative data; and finally, some functional and pathophysiological considerations, relating nigral organization to pathophysiology and hypotheses on the etiology and distribution of AD and PD. DAergic cell populations in the mesencephalon (SN pars compacta, VTA, and the retrorubral area A8) which give rise to well-developed, DAergic, mesotelencephalic pathways, including a distinct mesostriatal system, and a substance P-immunoreactive striatotegmental system which projects to the SN pars reticulata and VTA appear to be common to reptiles, birds, and mammals (Sect. 3.1). The extensive literature on the organization of the SN/VTA complex in rats is summarized in Sect. 3.2. The mesotelencephalic projection is organized along inverted dorsal to ventral, medial to lateral, and rostral to caudal topographies. A dense DAergic innervation is characteristic of the entire striatal complex, including the caudate-putamen (the dorsal striatum), the nucleus accumbens, and the olfactory tubercle (the ventral striatum). This mesostriatal projection is compartmentally organized with distinct sets of DAergic neurons projecting to striosomes and extrasriosomal matrix, respectively, suggesting specialized channels directed at DAergic modulation of sensorimotor processing in the striatal matrix and limbic related mechanisms represented in the striosomal system. The VTA and medial part of the SN give rise to the DAergic mesolimbocortical system with extensive projections to limbic, allocortical, and neocortical structures. The

  20. Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation.

    Science.gov (United States)

    Settell, Megan L; Testini, Paola; Cho, Shinho; Lee, Jannifer H; Blaha, Charles D; Jo, Hang J; Lee, Kendall H; Min, Hoon-Ki

    2017-01-01

    Background: The ventral tegmental area (VTA), containing mesolimbic and mesocortical dopaminergic neurons, is implicated in processes involving reward, addiction, reinforcement, and learning, which are associated with a variety of neuropsychiatric disorders. Electrical stimulation of the VTA or the medial forebrain bundle and its projection target the nucleus accumbens (NAc) is reported to improve depressive symptoms in patients affected by severe, treatment-resistant major depressive disorder (MDD) and depressive-like symptoms in animal models of depression. Here we sought to determine the neuromodulatory effects of VTA deep brain stimulation (DBS) in a normal large animal model (swine) by combining neurochemical measurements with functional magnetic resonance imaging (fMRI). Methods: Animals (n = 8 swine) were implanted with a unilateral DBS electrode targeting the VTA. During stimulation (130 Hz frequency, 0.25 ms pulse width, and 3 V amplitude), fMRI was performed. Following fMRI, fast-scan cyclic voltammetry in combination with carbon fiber microelectrodes was performed to quantify VTA-DBS-evoked dopamine release in the ipsilateral NAc. In a subset of swine, the blood oxygen level-dependent (BOLD) percent change evoked by stimulation was performed at increasing voltages (1, 2, and 3 V). Results: A significant increase in VTA-DBS-evoked BOLD signal was found in the following regions: the ipsilateral dorsolateral prefrontal cortex, anterior and posterior cingulate, insula, premotor cortex, primary somatosensory cortex, and striatum. A decrease in the BOLD signal was also observed in the contralateral parahippocampal cortex, dorsolateral and anterior prefrontal cortex, insula, inferior temporal gyrus, and primary somatosensory cortex (Bonferroni-corrected modulation of the neural circuitry associated with VTA-DBS was characterized in a large animal. Our findings suggest that VTA-DBS could affect the activity of neural systems and brain regions implicated in

  1. Episodic Social Stress-Escalated Cocaine Self-Administration: Role of Phasic and Tonic Corticotropin Releasing Factor in the Anterior and Posterior Ventral Tegmental Area

    Science.gov (United States)

    Boyson, Christopher O.; Montagud-Romero, Sandra; Stein, Dirson J.; Gobrogge, Kyle L.; DeBold, Joseph F.; Miczek, Klaus A.

    2016-01-01

    Intermittent social defeat stress escalates later cocaine self-administration. Reward and stress both activate ventral tegmental area (VTA) dopamine neurons, increasing downstream extracellular dopamine concentration in the medial prefrontal cortex and nucleus accumbens. The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1, CRF-R2) are located in the VTA and influence dopaminergic activity. These experiments explore how CRF release and the activation of its receptors within the VTA both during and after stress influence later cocaine self-administration in rats. In vivo microdialysis of CRF in the VTA demonstrated that CRF is phasically released in the posterior VTA (pVTA) during acute defeat, but, with repeated defeat, CRF is recruited into the anterior VTA (aVTA) and CRF tone is increased in both subregions. Intra-VTA antagonism of CRF-R1 in the pVTA and CRF-R2 in the aVTA during each social defeat prevented escalated cocaine self-administration in a 24 h “binge.” VTA CRF continues to influence cocaine seeking in stressed animals long after social defeat exposure. Unlike nonstressed controls, previously stressed rats show significant cocaine seeking after 15 d of forced abstinence. Previously stressed rats continue to express elevated CRF tone within the VTA and antagonism of pVTA CRF-R1 or aVTA CRF-R2 reverses cocaine seeking. In conclusion, these experiments demonstrate neuroadaptive changes in tonic and phasic CRF with repeated stress, that CRF release during stress may contribute to later escalated cocaine taking, and that persistently elevated CRF tone in the VTA may drive later cocaine seeking through increased activation of pVTA CRF-R1 and aVTA CRF-R2. SIGNIFICANCE STATEMENT Corticotropin releasing factor (CRF) within the ventral tegmental area (VTA) has emerged as a likely candidate molecule underlying the fundamental link between stress history and escalated drug self-administration. However, the nature of CRF

  2. Tegmental-type primary pontine hemorrhage with mesencephalic extension. Clinico-CT-anatomic correlations

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Noboru; Ishikawa, Hiroshi; Kaneko, Mitsuo; Tanaka, Keisei

    1983-06-01

    In nine autopsy cases of tegmental-type primary pontine hemorrhage, two cases with a mesencephalic extension which was not accurately diagnosed symptomatologically, but which was clearly detected on CT films, were found. Correlative clinico-CT-anatomic reports on this kind of pontine hemorrhage have not been included in the literature. The two patients were both females, 73 and 53 years old. Both were hypertensive and under medical care. They showed disturbances of consciousness and respiration, pin-point pupils, fixed eyes in the midposition, right hemiplegia, right extensor plantar response, etc., but both responded well to painful stimuli on the left half of the body. CT examinations detected a continuous high-density area in the left-sided tegmentum of the pons and midbrain. They died 9 and 21 days later respectively. With the help of an electronic image analyser, a great volume of hematoma was measured in the postmortem brainstem in these cases (17 ml and 14 ml). Precise analyses of the correlations among clinical symptomatology, CT, and anatomical findings, and histological examinations were carried out in an attempt to find the pathogenesis of this disease. In the diagnosis of tegmental-type primary pontine hemorrhage, attention should be paid to a possible mesencephalic involvement as one of the modes of hematoma extension, although it may be rather rare.

  3. Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of the Ghrelin Receptor in the Ventral Tegmental Area

    DEFF Research Database (Denmark)

    Skov, Louise J; Jensen, Morten; Christiansen, Søren H

    2017-01-01

    Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-R(VTA) mice) to spec...

  4. Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area

    NARCIS (Netherlands)

    Dremencov, Eliyahu; El Mansari, Mostafa; Blier, Pierre

    Background: Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are efficacious in depression because of their ability to increase 5-HT neurotransmission. However, owing to a purported inhibitory effect of 5- HT on dopamine (DA) neuronal activity in the ventral tegmental area (VTA), this increase

  5. Study of Relativistic Nucleus - Nucleus Collisions

    CERN Multimedia

    2002-01-01

    The aim of the experiment is to survey the reaction mechanisms involved in the collision of 60~GeV/nucleon and 200~GeV/nucleon light ions ($^{16}$0 and $^{32}$S provided by a new GSI-LBL injector) with different nuclei, to determine the stopping power of nuclear matter and to search for evidence of the formation of quark matter by comparison to hadron-nucleus reactions at the same incident energies. \\\\ The experimental set-up consists of a 2 m Streamer Chamber in the Vertex Magnet used to detect all the charged particles emerging from the interaction as well as the neutral strange particles that decay inside the chamber. The high energy of the forward-going particles are detected by four sets of calorimeters. A highly segmented Photon Position Detector (PPD) backed up by a 240 segment Ring Calorimeter will cover one unit of rapidity around mid-rapidity. An Intermediate Calorimeter will cover the rest of the forward phase space except for the region around beam rapidity, where a Veto Calorimeter will detect be...

  6. Mere Exposure: Preference Change for Novel Drinks Reflected in Human Ventral Tegmental Area.

    Science.gov (United States)

    Ballard, Ian C; Hennigan, Kelly; McClure, Samuel M

    2017-05-01

    Preferences for novel stimuli tend to develop slowly over many exposures. Psychological accounts of this effect suggest that it depends on changes in the brain's valuation system. Participants consumed a novel fluid daily for 10 days and underwent fMRI on the first and last days. We hypothesized that changes in activation in areas associated with the dopamine system would accompany changes in preference. The change in activation in the ventral tegmental area (VTA) between sessions scaled with preference change. Furthermore, a network comprising the sensory thalamus, posterior insula, and ventrolateral striatum showed differential connectivity with the VTA that correlated with individual changes in preference. Our results suggest that the VTA is centrally involved in both assigning value to sensory stimuli and influencing downstream regions to translate these value signals into subjective preference. These results have important implications for models of dopaminergic function and behavioral addiction.

  7. Neurotensin Receptor-1 Identifies a Subset of Ventral Tegmental Dopamine Neurons that Coordinates Energy Balance

    Directory of Open Access Journals (Sweden)

    Hillary L. Woodworth

    2017-08-01

    Full Text Available Dopamine (DA neurons in the ventral tegmental area (VTA are heterogeneous and differentially regulate ingestive and locomotor behaviors that affect energy balance. Identification of which VTA DA neurons mediate behaviors that limit weight gain has been hindered, however, by the lack of molecular markers to distinguish VTA DA populations. Here, we identified a specific subset of VTA DA neurons that express neurotensin receptor-1 (NtsR1 and preferentially comprise mesolimbic, but not mesocortical, DA neurons. Genetically targeted ablation of VTA NtsR1 neurons uncouples motivated feeding and physical activity, biasing behavior toward energy expenditure and protecting mice from age-related and diet-induced weight gain. VTA NtsR1 neurons thus represent a molecularly defined subset of DA neurons that are essential for the coordination of energy balance. Modulation of VTA NtsR1 neurons may therefore be useful to promote behaviors that prevent the development of obesity.

  8. Prominent burst firing of dopaminergic neurons in the ventral tegmental area during paradoxical sleep.

    Science.gov (United States)

    Dahan, Lionel; Astier, Bernadette; Vautrelle, Nicolas; Urbain, Nadia; Kocsis, Bernat; Chouvet, Guy

    2007-06-01

    Dopamine is involved in motivation, memory, and reward processing. However, it is not clear whether the activity of dopamine neurons is related or not to vigilance states. Using unit recordings in unanesthetized head restrained rats we measured the firing pattern of dopamine neurons of the ventral tegmental area across the sleep-wake cycle. We found these cells were activated during paradoxical sleep (PS) via a clear switch to a prominent bursting pattern, which is known to induce large synaptic dopamine release. This activation during PS was similar to the activity measured during the consumption of palatable food. Thus, as it does during waking in response to novelty and reward, dopamine could modulate brain plasticity and thus participate in memory consolidation during PS. By challenging the traditional view that dopamine is the only aminergic group not involved in sleep physiology, this study provides an alternative perspective that may be crucial for understanding the physiological function of PS and dream mentation.

  9. Dopamine Neurons in the Ventral Tegmental Area: An Autopsy Case of Disorganized Type of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Keiko Ikemoto

    2011-01-01

    Full Text Available The mesolimbic dopamine (DA system has been associated with the pathogenesis of schizophrenia. Here, we examined DA-containing neuronal structures of the ventral tegmental area (VTA of an autopsy case of disorganized type of schizophrenia (75-year-old female, using tyrosine hydroxylase (TH immunohistochemistry. A free floating method using 50-μm cryostat sections and three-dimensional imaging analyzer AxioVision were applied to observe the wide range structures of TH-immunoreactive (-ir neurons. TH-ir neuronal cell bodies in the VTA of the present case had irregular shape and various size, and TH-ir neuronal processes had irregular thickness and straightened shape or curved shape having many corners, when compared to a control autopsy case with no detectable neurological and psychiatric diseases (64-year-old male. The mechanisms underlying the morphological characteristics of DA neurons of the brains with schizophrenia should be elucidated epigenetically as well as genetically.

  10. A pomeron approach to hadron-nucleus and nucleus-nucleus 'soft' interaction at high energy

    CERN Document Server

    Bondarenko, S; Levin, E; Maor, U

    2001-01-01

    We formulate a generalization of the Glauber formalism for hadron-nucleus and nucleus-nucleus collisions based on the pomeron approach to high-energy interaction. Our treatment is based on two physical assumptions (i.e. two small parameters): (i) that only sufficiently small distances contribute to the pomeron structure; and (ii) the triple-pomeron vertex G sub 3 sub P /g sub P sub N <<1 (where g sub P sub N is the pomeron-nucleon vertex) is small. A systematic method is developed for calculating the total, elastic and diffractive dissociation cross sections as well as the survival probability of large rapidity gap processes and inclusive observables, both for hadron-nucleus and nucleus-nucleus collisions. Our approach suggests saturation of the density of the produced hadrons in nucleus-nucleus collisions, the value of the saturation density turns out to be large.

  11. Prenatal nicotine is associated with reduced AMPA and NMDA receptor-mediated rises in calcium within the laterodorsal tegmentum: a pontine nucleus involved in addiction processes

    DEFF Research Database (Denmark)

    Mc Nair, Laura Kristine Frendrup; Kohlmeier, Kristi Anne

    2015-01-01

    this nucleus. Accordingly, we used calcium imaging, to evaluate AMPA and NMDA receptor-mediated calcium responses in LDT brain slices from control and PNE mice. We also investigated whether the positive AMPA receptor modulator cyclothiazide (CYZ) had differential actions on calcium in the LDT following PNE...... in the LDT of PNE mice when compared with enhancements in responses in control LDT cells. Immunohistochemical processing confirmed that calcium imaging recordings were obtained from the LDT nucleus as determined by presence of cholinergic neurons. Our results contribute to the body of evidence suggesting...... excitatory neurotransmitter within the laterodorsal tegmental nucleus (LDT), which is a brainstem region importantly involved in responding to motivational stimuli and critical in development of drug addiction-associated behaviours, however, it is unknown whether PNE alters glutamate signalling within...

  12. Elevated expression of serotonin 5-HT2A receptors in the rat ventral tegmental area enhances vulnerability to the behavioral effects of cocaine

    Directory of Open Access Journals (Sweden)

    David V. Herin

    2013-02-01

    Full Text Available The dopamine mesocorticoaccumbens pathway which originates in the ventral tegmental area (VTA and projects to the nucleus accumbens and prefrontal cortex is a circuit important in mediating the actions of psychostimulants. The function of this circuit is modulated by the actions of serotonin (5-HT at 5-HT2A receptors (5-HT2AR localized to the VTA. In the present study, we tested the hypothesis that virally-mediated overexpression of 5-HT2AR in the VTA would increase cocaine-evoked locomotor activity in the absence of alterations in basal locomotor activity. A plasmid containing the gene for the 5-HT2AR linked to a synthetic marker peptide (Flag was created and the construct was packaged in an adeno-associated virus vector (rAAV-5-HT2AR-Flag. This viral vector (2 µl; 109-10 transducing units/ml was unilaterally infused into the VTA of male rats, while control animals received an intra-VTA infusion of Ringer’s solution. Virus-pretreated rats exhibited normal spontaneous locomotor activity measured in a modified open-field apparatus at 7, 14, and 21 days following infusion. After an injection of cocaine (15 mg/kg, ip, both horizontal hyperactivity and rearing were significantly enhanced in virus-treated rats (p<0.05. Immunohistochemical analysis confirmed expression of Flag and overexpression of the 5-HT2AR protein. These data indicate that the vulnerability of adult male rats to hyperactivity induced by cocaine is enhanced following increased levels of expression of the 5-HT2AR in the VTA and suggest that the 5-HT2AR receptor in the VTA plays a role in regulation of responsiveness to cocaine.

  13. Characterization of cognitive deficits in rats overexpressing human alpha-synuclein in the ventral tegmental area and medial septum using recombinant adeno-associated viral vectors.

    Science.gov (United States)

    Hall, Hélène; Jewett, Michael; Landeck, Natalie; Nilsson, Nathalie; Schagerlöf, Ulrika; Leanza, Giampiero; Kirik, Deniz

    2013-01-01

    Intraneuronal inclusions containing alpha-synuclein (a-syn) constitute one of the pathological hallmarks of Parkinson's disease (PD) and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP) in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration.

  14. The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems.

    Science.gov (United States)

    Ding, Zheng-Ming; Ingraham, Cynthia M; Rodd, Zachary A; McBride, William J

    2015-05-01

    Ethanol can be self-infused directly into the posterior ventral tegmental area (pVTA) and these effects involve activation of local dopamine neurons. However, the neuro-circuitry beyond the pVTA involved in these reinforcing effects has not been explored. Intra-pVTA microinjection of ethanol increases dopamine release in the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and ventral pallidum (VP). The present study tested the hypothesis that the reinforcing effects of ethanol within the pVTA involve the activation of dopamine projections from the pVTA to the NAC, VP and mPFC. Following the acquisition of self-infusions of 200 mg% ethanol into the pVTA, either the dopamine D2 receptor antagonist sulpiride (0, 10 or 100 μM) or the D1 receptor antagonist SCH-23390 (0, 10 or 100 μM) was microinjected into the ipsilateral NAC shell (NACsh), NAC core (NACcr), VP or mPFC immediately prior to the self-infusion sessions to assess the involvement of the different dopamine projections in the reinforcing effects of ethanol. Microinjection of each compound at higher concentration into the NACsh, VP or mPFC, but not the NACcr, significantly reduced the responses on the active lever (from 40-50 to approximately 20 responses). These results indicate that activation of dopamine receptors in the NACsh, VP or mPFC, but not the NACcr, is involved in mediating the reinforcing effects of ethanol in the pVTA, suggesting that the 'alcohol reward' neuro-circuitry consist of, at least in part, activation of the dopamine projections from the pVTA to the NACsh, VP and mPFC. © 2014 Society for the Study of Addiction.

  15. Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

    Science.gov (United States)

    Christensen, Mark H.; Ishibashi, Masaru; Nielsen, Michael L.; Leonard, Christopher S.; Kohlmeier, Kristi A.

    2015-01-01

    The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on several parameters affecting LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine was found to induce larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age. PMID:24863041

  16. Characterization of cognitive deficits in rats overexpressing human alpha-synuclein in the ventral tegmental area and medial septum using recombinant adeno-associated viral vectors.

    Directory of Open Access Journals (Sweden)

    Hélène Hall

    Full Text Available Intraneuronal inclusions containing alpha-synuclein (a-syn constitute one of the pathological hallmarks of Parkinson's disease (PD and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration.

  17. Overexpression of BDNF in the ventral tegmental area enhances binge cocaine self-administration in rats exposed to repeated social defeat.

    Science.gov (United States)

    Wang, Junshi; Bastle, Ryan M; Bass, Caroline E; Hammer, Ronald P; Neisewander, Janet L; Nikulina, Ella M

    2016-10-01

    Stress is a major risk factor for substance abuse. Intermittent social defeat stress increases drug self-administration (SA) and elevates brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA) in rats. Intra-VTA BDNF overexpression enhances social defeat stress-induced cross-sensitization to psychostimulants and induces nucleus accumbens (NAc) ΔFosB expression. Therefore, increased VTA BDNF may mimic or augment the development of drug abuse-related behavior following social stress. To test this hypothesis, adeno-associated virus (AAV) was infused into the VTA to overexpress either GFP alone (control) or GFP + BDNF. Rats were then either handled or exposed to intermittent social defeat stress before beginning cocaine SA training. The SA acquisition and maintenance phases were followed by testing on a progressive ratio (PR) schedule of cocaine reinforcement, and then during a 12-h access "binge" cocaine SA session. BDNF and ΔFosB were quantified postmortem in regions of the mesocorticolimbic circuitry using immunohistochemistry. Social defeat stress increased cocaine intake on a PR schedule, regardless of virus treatment. While stress alone increased intake during the 12-h binge session, socially-defeated rats that received VTA BDNF overexpression exhibited even greater cocaine intake compared to the GFP-stressed group. However, VTA BDNF overexpression alone did not alter binge intake. BDNF expression in the VTA was also positively correlated with total cocaine intake during binge session. VTA BDNF overexpression increased ΔFosB expression in the NAc, but not in the dorsal striatum. Here we demonstrate that VTA BDNF overexpression increases long-access cocaine intake, but only under stressful conditions. Therefore, enhanced VTA-BDNF expression may be a facilitator for stress-induced increases in drug abuse-related behavior specifically under conditions that capture compulsive-like drug intake. Copyright © 2016 Elsevier Ltd. All

  18. Nucleus-Nucleus Collision as Superposition of Nucleon-Nucleus Collisions

    Energy Technology Data Exchange (ETDEWEB)

    Orlova, G.I.; Adamovich, M.I.; Aggarwal, M.M.; Alexandrov, Y.A.; Andreeva, N.P.; Badyal, S.K.; Basova, E.S.; Bhalla, K.B.; Bhasin, A.; Bhatia, V.S.; Bradnova, V.; Bubnov, V.I.; Cai, X.; Chasnikov, I.Y.; Chen, G.M.; Chernova, L.P.; Chernyavsky, M.M.; Dhamija, S.; Chenawi, K.El; Felea, D.; Feng, S.Q.; Gaitinov, A.S.; Ganssauge, E.R.; Garpman, S.; Gerassimov, S.G.; Gheata, A.; Gheata, M.; Grote, J.; Gulamov, K.G.; Gupta, S.K.; Gupta, V.K.; Henjes, U.; Jakobsson, B.; Kanygina, E.K.; Karabova, M.; Kharlamov, S.P.; Kovalenko, A.D.; Krasnov, S.A.; Kumar, V.; Larionova, V.G.; Li, Y.X.; Liu, L.S.; Lokanathan, S.; Lord, J.J.; Lukicheva, N.S.; Lu, Y.; Luo, S.B.; Mangotra, L.K.; Manhas, I.; Mittra, I.S.; Musaeva, A.K.; Nasyrov, S.Z.; Navotny, V.S.; Nystrand, J.; Otterlund, I.; Peresadko, N.G.; Qian, W.Y.; Qin, Y.M.; Raniwala, R.; Rao, N.K.; Roeper, M.; Rusakova, V.V.; Saidkhanov, N.; Salmanova, N.A.; Seitimbetov, A.M.; Sethi, R.; Singh, B.; Skelding, D.; Soderstrem, K.; Stenlund, E.; Svechnikova, L.N.; Svensson, T.; Tawfik, A.M.; Tothova, M.; Tretyakova, M.I.; Trofimova, T.P.; Tuleeva, U.I.; Vashisht, Vani; Vokal, S.; Vrlakova, J.; Wang, H.Q.; Wang, X.R.; Weng, Z.Q.; Wilkes, R.J.; Yang, C.B.; Yin, Z.B.; Yu, L.Z.; Zhang, D.H.; Zheng, P.Y.; Zhokhova, S.I.; Zhou, D.C

    1999-03-01

    Angular distributions of charged particles produced in {sup 16}O and {sup 32}S collisions with nuclear track emulsion were studied at momenta 4.5 and 200 A GeV/c. Comparison with the angular distributions of charged particles produced in proton-nucleus collisions at the same momentum allows to draw the conclusion, that the angular distributions in nucleus-nucleus collisions can be seen as superposition of the angular distributions in nucleon-nucleus collisions taken at the same impact parameter b{sub NA}, that is mean impact parameter between the participating projectile nucleons and the center of the target nucleus.

  19. Neutrino-nucleus interactions

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, H.; /Tufts U.; Garvey, G.; /Los Alamos; Zeller, G.P.; /Fermilab

    2011-01-01

    The study of neutrino oscillations has necessitated a new generation of neutrino experiments that are exploring neutrino-nuclear scattering processes. We focus in particular on charged-current quasi-elastic scattering, a particularly important channel that has been extensively investigated both in the bubble-chamber era and by current experiments. Recent results have led to theoretical reexamination of this process. We review the standard picture of quasi-elastic scattering as developed in electron scattering, review and discuss experimental results, and discuss additional nuclear effects such as exchange currents and short-range correlations that may play a significant role in neutrino-nucleus scattering.

  20. Higgs-Boson Production in Nucleus-Nucleus Collisions

    Science.gov (United States)

    Norbury, John W.

    1992-01-01

    Cross section calculations are presented for the production of intermediate-mass Higgs bosons produced in ultrarelativistic nucleus-nucleus collisions via two photon fusion. The calculations are performed in position space using Baur's method for folding together the Weizsacker-Williams virtual-photon spectra of the two colliding nuclei. It is found that two photon fusion in nucleus-nucleus collisions is a plausible way of finding intermediate-mass Higgs bosons at the Superconducting Super Collider or the CERN Large Hadron Collider.

  1. Rescattering effects and intermittent exponents in nucleus-nucleus interactions

    Energy Technology Data Exchange (ETDEWEB)

    Pajares, C. (Universidad de Santiago de Compostela (Spain). Dept. de Particulas Elementales)

    1991-04-11

    It is shown that the rescattering in nucleus-nucleus collisions provides a natural branching mechanism which explains the dependence of the intermittent exponents on the energy, projectile and target. The possibility of finding some new coherent phenomena by studying the dependence of the intermittent exponents on the number of collisions is discussed. (orig.).

  2. Conjunctive encoding of movement and reward by ventral tegmental area neurons in the freely navigating rodent

    Science.gov (United States)

    Puryear, Corey B.; Kim, Min Jung; Mizumori, Sheri J.Y.

    2010-01-01

    As one of the two main sources of brain dopamine, the ventral tegmental area (VTA) is important for several complex functions, including motivation, reward prediction, and contextual learning. Although many studies have identified the potential neural substrate of VTA dopaminergic activity in reward prediction functions during Pavlovian and operant conditioning tasks, less is understood about the role of VTA neuronal activity in motivated behaviors and more naturalistic forms of context-dependent learning. Therefore, VTA neural activity was recorded as rats performed a spatial memory task under varying context conditions. In addition to reward- and reward predicting cue-related firing commonly observed during conditioning tasks, the activity of a large proportion of VTA neurons was also related to the velocity and/or acceleration of the animal’s movement. Importantly, movement-related activity was strongest when rats displayed more motivation to obtain reward. Furthermore, many cells displayed a dual code of movement- and reward-related activity. These two modes of firing, however, were differentially regulated by context information, suggesting that movement- and reward-related firing are two independently regulated modes of VTA neuronal activity and may serve separate functions. PMID:20364883

  3. Electrical Stimulation of the Ventral Tegmental Area Induces Reanimation from General Anesthesia

    Science.gov (United States)

    Solt, Ken; Van Dort, Christa J.; Chemali, Jessica J.; Taylor, Norman E.; Kenny, Jonathan D.; Brown, Emery N.

    2014-01-01

    BACKGROUND Methylphenidate or a D1 dopamine receptor agonist induce reanimation (active emergence) from general anesthesia. We tested whether electrical stimulation of dopaminergic nuclei also induces reanimation from general anesthesia. METHODS In adult rats, a bipolar insulated stainless steel electrode was placed in the ventral tegmental area (VTA, n = 5) or substantia nigra (SN, n = 5). After a minimum 7-day recovery period, the isoflurane dose sufficient to maintain loss of righting was established. Electrical stimulation was initiated and increased in intensity every 3 min to a maximum of 120μA. If stimulation restored the righting reflex, an additional experiment was performed at least 3 days later during continuous propofol anesthesia. Histological analysis was conducted to identify the location of the electrode tip. In separate experiments, stimulation was performed in the prone position during general anesthesia with isoflurane or propofol, and the electroencephalogram was recorded. RESULTS To maintain loss of righting, the dose of isoflurane was 0.9% ± 0.1 vol%, and the target plasma dose of propofol was 4.4 μg/ml ± 1.1 μg/ml (mean ± SD). In all rats with VTA electrodes, electrical stimulation induced a graded arousal response including righting that increased with current intensity. VTA stimulation induced a shift in electroencephalogram peak power from δ (anesthesia with isoflurane or propofol. These results are consistent with the hypothesis that dopamine release by VTA, but not SN, neurons induces reanimation from general anesthesia. PMID:24398816

  4. ALPHA-1 ADRENORECEPTORS MODULATE GABA RELEASE ONTO VENTRAL TEGMENTAL AREA DOPAMINE NEURONS

    Science.gov (United States)

    Velásquez-Martínez, M.C.; Vázquez-Torres, R.; Rojas, L.V.; Sanabria, P.; Jiménez-Rivera, C.A.

    2014-01-01

    The ventral tegmental area (VTA) plays an important role in reward and motivational processes involved in drug addiction. Previous studies have shown that alpha1-adrenoreceptors (α1-AR) are primarily found presynaptically at this area. We hypothesized that GABA released onto VTA-dopamine (DA) cells is modulated by presynaptic α1-AR. Recordings were obtained from putative VTA-DA cells of male Sprague-Dawley rats (28–50 days postnatal) using whole-cell voltage clamp technique. Phenylephrine (10µM; α1-AR agonist) decreased the amplitude of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) evoked by electrical stimulation of afferent fibers (n=7; p0.05). Phenylephrine in low Ca2+ (1mM) medium decreased IPSC amplitude (n=7; p<0.05). Chelerythrine (a protein kinase C inhibitor) blocked the α1-AR action on IPSC amplitude (n=6; p<0.05). Phenylephrine failed to decrease IPSCs amplitude in the presence of paxilline, a BK channel blocker (n=7; p<0.05). Taken together, these results demonstrate that α1-ARs at presynaptic terminals can modulate GABA release onto VTA-DA cells. Drug-induced changes in α1-AR could contribute to the modifications occurring in the VTA during the addiction process. PMID:25261018

  5. Stimulation of the mesencephalic ventral tegmental area blunts the sensitivity of cardiac baroreflex in decerebrate cats.

    Science.gov (United States)

    Matsukawa, Kanji; Ishii, Kei; Ishida, Tomoko; Nagai, Atsushi; Liang, Nan

    2015-05-01

    We have examined for the first time whether electrical stimulation of the mesencephalic ventral tegmental area (VTA) or the substantia nigra (SN) was capable of suppressing cardiac baroreflex sensitivity in decerebrate cats. After decerebration was performed by electrocoagulation at the precollicular-premammillary level and inhalation anesthesia was stopped, the animals were able to show spontaneous motor activity intermittently. Electrical stimulations of the mesencephalic areas (the VTA and SN) for 30s were conducted with a monopolar tungsten microelectrode (current intensity of pulse trains, 50-100 μA; frequency, 40-50 Hz; pulse duration, 0.5-1.0 ms), without producing tibial motor discharge. Stimulation of the VTA evoked the significant increases in heart rate (HR, 12 ± 2 beats/min) and mean arterial blood pressure (MAP, 12 ± 3 mm Hg). When the baroreflex bradycardia and the slope of the cardiac baroreflex curve were examined using a pressor response with brief occlusion of the abdominal aorta, the VTA stimulation blunted both the baroreflex bradycardia and the maximal slope of the baroreflex MAP-HR curve by 63-74% in the same manner as spontaneously-evoked motor activity. In contrast, stimulation of the SN elicited no modulation of cardiac baroreflex. It is likely that stimulation of the mesencephalic VTA suppresses cardiac baroreflex sensitivity and has the similar features of the effects on the cardiac baroreflex function as those during spontaneously-evoked motor activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Coordinated activity of ventral tegmental neurons adapts to appetitive and aversive learning.

    Directory of Open Access Journals (Sweden)

    Yunbok Kim

    Full Text Available Our understanding of how value-related information is encoded in the ventral tegmental area (VTA is based mainly on the responses of individual putative dopamine neurons. In contrast to cortical areas, the nature of coordinated interactions between groups of VTA neurons during motivated behavior is largely unknown. These interactions can strongly affect information processing, highlighting the importance of investigating network level activity. We recorded the activity of multiple single units and local field potentials (LFP in the VTA during a task in which rats learned to associate novel stimuli with different outcomes. We found that coordinated activity of VTA units with either putative dopamine or GABA waveforms was influenced differently by rewarding versus aversive outcomes. Specifically, after learning, stimuli paired with a rewarding outcome increased the correlation in activity levels between unit pairs whereas stimuli paired with an aversive outcome decreased the correlation. Paired single unit responses also became more redundant after learning. These response patterns flexibly tracked the reversal of contingencies, suggesting that learning is associated with changing correlations and enhanced functional connectivity between VTA neurons. Analysis of LFP recorded simultaneously with unit activity showed an increase in the power of theta oscillations when stimuli predicted reward but not an aversive outcome. With learning, a higher proportion of putative GABA units were phase locked to the theta oscillations than putative dopamine units. These patterns also adapted when task contingencies were changed. Taken together, these data demonstrate that VTA neurons organize flexibly as functional networks to support appetitive and aversive learning.

  7. Neuron-type-specific signals for reward and punishment in the ventral tegmental area.

    Science.gov (United States)

    Cohen, Jeremiah Y; Haesler, Sebastian; Vong, Linh; Lowell, Bradford B; Uchida, Naoshige

    2012-01-18

    Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error), but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We 'tagged' dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.

  8. Administration of the GABAA receptor antagonist picrotoxin into rat supramammillary nucleus induces c-Fos in reward-related brain structures. Supramammillary picrotoxin and c-Fos expression

    Directory of Open Access Journals (Sweden)

    Shin Rick

    2010-08-01

    Full Text Available Abstract Background Picrotoxin blocks GABAA receptors, whose activation typically inhibits neuronal firing activity. We recently found that rats learn to selectively self-administer picrotoxin or bicuculline, another GABAA receptor antagonist, into the supramammillary nucleus (SuM, a posterior hypothalamic structure localized anterior to the ventral tegmental area. Other drugs such as nicotine or the excitatory amino acid AMPA are also self-administered into the SuM. The SuM appears to be functionally linked with the mesolimbic dopamine system and is closely connected with other brain structures that are implicated in motivational processes, including the prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus. Here, we hypothesized that these brain structures are activated by picrotoxin injections into the SuM. Results Picrotoxin administration into the SuM markedly facilitated locomotion and rearing. Further, it increased c-Fos expression in this region, suggesting blockade of tonic inhibition and thus the disinhibition of local neurons. This manipulation also increased c-Fos expression in structures including the ventral tegmental area, medial shell of the nucleus accumbens, medial prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus. Conclusions Picrotoxin administration into the SuM appears to disinhibit local neurons and recruits activation of brain structures associated with motivational processes, including the mesolimbic dopamine system, prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus. These regions may be involved in mediating positive motivational effects triggered by intra-SuM picrotoxin.

  9. The intercalatus nucleus of Staderini.

    Science.gov (United States)

    Cascella, Marco

    2016-01-01

    Rutilio Staderini was one of the leading Italian anatomists of the twentieth century, together with some scientists, such as Giulio Chiarugi, Giovanni Vitali, and others. He was also a member of a new generation of anatomists. They had continued the tradition of the most famous Italian scientists, which started from the Renaissance up until the nineteenth century. Although he carried out important studies of neuroanatomy and comparative anatomy, as well as embryology, his name is rarely remembered by most medical historians. His name is linked to the nucleus he discovered: the Staderini nucleus or intercalated nucleus, a collection of nerve cells in the medulla oblongata located lateral to the hypoglossal nucleus. This article focuses on the biography of the neuroanatomist as well as the nucleus that carries his name and his other research, especially on comparative anatomy and embryology.

  10. Salsolinol facilitates glutamatergic transmission to dopamine neurons in the posterior ventral tegmental area of rats.

    Directory of Open Access Journals (Sweden)

    Guiqin Xie

    Full Text Available Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D(1 receptors (D(1Rs. In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D(1Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D(1R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D(1Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol.

  11. Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

    Science.gov (United States)

    Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

    2010-01-01

    Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction. PMID:21187978

  12. Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Liu

    2010-12-01

    Full Text Available Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP and long-term depression (LTD. Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses of the midbrain ventral tegmental area (VTA following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids, the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

  13. Acute fasting increases somatodendritic dopamine release in the ventral tegmental area.

    Science.gov (United States)

    Roseberry, Aaron G

    2015-08-01

    Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active. Copyright © 2015 the American Physiological Society.

  14. In vivo measurement of somatodendritic release of dopamine in the ventral tegmental area.

    Science.gov (United States)

    Kita, Justin M; Kile, Brian M; Parker, Lauren E; Wightman, R Mark

    2009-11-01

    The ventral tegmental area (VTA), the locus of mesolimbic dopamine cell bodies, contains dopamine. Experiments in brain slices have demonstrated that VTA dopamine can be released by local electrical stimulation. Measurements with both push-pull cannula and microdialysis in intact animals have also obtained evidence for releasable dopamine. Here we demonstrate that dopamine release in the VTA can be evoked by remote stimulations of the medial forebrain bundle (MFB) in the anesthetized rat. In initial experiments, the MFB was electrically stimulated while a carbon-fiber electrode was lowered to the VTA, with recording by fast-scan cyclic voltammetry. While release was not observed with the carbon fiber 4-6 mm below dura, a voltammetric response was observed at 6-8 mm below dura, but the voltammogram was poorly defined. At lower depths, in the VTA, dopamine release was evoked. Immunohistochemistry experiments with antibodies for tyrosine hydroxylase (TH) confirmed that dopamine processes were primarily found below 8 mm. Similarly, tissue content determined by liquid chromatography revealed serotonin but not dopamine dorsal to 8 mm with both dopamine and serotonin at lower depths. Evaluation of the VTA signal by pharmacological means showed that it increased with inhibitors of dopamine uptake, but release was not altered by D2 agents. Dopamine release in the VTA was frequency dependent and could be exhausted by stimulations longer than 5 s. Thus, VTA dopamine release can be evoked in vivo by remote stimulations and it resembles release in terminal regions, possessing a similar uptake mechanism and a finite releasable storage pool.

  15. Neurotrophins in the ventral tegmental area: Role in social stress, mood disorders and drug abuse.

    Science.gov (United States)

    Nikulina, E M; Johnston, C E; Wang, J; Hammer, R P

    2014-12-12

    This review discusses the impact of neurotrophins and other trophic factors, including fibroblast growth factor and glial cell line-derived neurotrophic factor, on mood disorders, weight regulation and drug abuse, with an emphasis on stress- and drug-induced changes in the ventral tegmental area (VTA). Neurotrophins, comprising nerve growth factor, brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4/5 play important roles in neuronal plasticity and the development of different psychopathologies. In the VTA, most research has focused on the role of BDNF, because other neurotrophins are not found there in significant quantities. BDNF originating in the VTA provides trophic support to dopamine neurons. The diverse intracellular signaling pathways activated by BDNF may underlie precise physiological functions specific to the VTA. In general, VTA BDNF expression increases after psychostimulant exposures, and enhanced BDNF level in the VTA facilitates psychostimulant effects. The impact of VTA BDNF on the behavioral effects of psychostimulants relies primarily on its action within the mesocorticolimbic circuit. In the case of opiates, VTA BDNF expression and effects seem to be dependent on whether an animal is drug-naïve or has a history of drug use, only the latter of which is related to dopamine mechanisms. Social defeat stress that is continuous in mice or intermittent in rats increases VTA BDNF expression, and is associated with depressive and social avoidance behaviors. Intermittent social defeat stress induces persistent VTA BDNF expression that triggers psychostimulant cross-sensitization. Understanding the cellular and molecular substrates of neurotrophin effects may lead to novel therapeutic approaches for the prevention and treatment of substance use and mood disorders. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Theta activity in local field potential of the ventral tegmental area in sleeping and waking rats.

    Science.gov (United States)

    Orzeł-Gryglewska, Jolanta; Matulewicz, Paweł; Jurkowlaniec, Edyta

    2014-05-15

    Hippocampal theta rhythm appears in two vigilance states: active waking and paradoxical sleep. The ventral tegmental area (VTA) is active in sleep and waking and is connected to the hippocampus. We assessed the relationship between local field potential (LFP) of the VTA and sleep-waking stages in freely moving rats. Electrical activity of the VTA was divided into: quiet waking (W), waking with theta (WT), slow wave sleep (SWS) and paradoxical sleep (PS), depending on the hippocampal signal and the animal's behavior. We analyzed total power in the VTA signal and we also extracted peak power (Pmax) and corresponding frequency (Fmax) in theta and delta bands from both the VTA and hippocampal recording. In the VTA the 6-9 Hz band had the highest power during PS, and the ratio of the 6-9 to 3-6 Hz power was highest during both PS and WT, which accentuated Pmax of this particular theta sub-band. During W, a very slight increase (or plateau) in signal power was seen in theta range. Pmax and Fmax of theta were higher in PS than in both WT and W, and these parameters did not differ between W and WT. During WT and PS, Fmax in the 6-9 Hz band was greatly correlated between the VTA and hippocampus signal. We also detected high cross-correlation in power spectra between the hippocampus and the VTA (for delta and theta, during WT and PS). The results suggest that the VTA may belong to the broad network involved in theta rhythm induction. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

    Science.gov (United States)

    Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

    2010-12-20

    Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

  18. Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol.

    Directory of Open Access Journals (Sweden)

    Bertha J Vandegrift

    Full Text Available Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2, the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2 or estrus (low E2 for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780 reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.

  19. The Rostromedial Tegmental Nucleus (RMTg), a GABAergic Afferent to Midbrain Dopamine Neurons, Encodes Aversive Stimuli and Inhibits Motor Responses

    National Research Council Canada - National Science Library

    Jhou, Thomas C; Fields, Howard L; Baxter, Mark G; Saper, Clifford B; Holland, Peter C

    2009-01-01

    .... RMTg lesions markedly reduce passive fear behaviors (freezing, open-arm avoidance) dependent on the extended amygdala, periaqueductal gray, or septum, all regions that project directly to the RMTg...

  20. BDNF overexpression in the ventral tegmental area prolongs social defeat stress-induced cross-sensitization to amphetamine and increases ΔFosB expression in mesocorticolimbic regions of rats.

    Science.gov (United States)

    Wang, Junshi; Fanous, Sanya; Terwilliger, Ernest F; Bass, Caroline E; Hammer, Ronald P; Nikulina, Ella M

    2013-10-01

    Social defeat stress induces persistent cross-sensitization to psychostimulants, but the molecular mechanisms underlying the development of cross-sensitization remain unclear. One candidate is brain-derived neurotrophic factor (BDNF). The present research examined whether ventral tegmental area (VTA) BDNF overexpression would prolong the time course of cross-sensitization after a single social defeat stress, which normally produces transient cross-sensitization lasting AAV-BDNF) vector resulted in a twofold increase of BDNF level in comparison to the group receiving the control virus (AAV-GFP), which lasted at least 45 days. Additionally, overexpression of BDNF in the VTA alone increased ΔFosB in the nucleus accumbens (NAc) and prefrontal cortex. Fourteen days after viral infusions, a separate group of rats underwent a single social defeat stress or control handling and were challenged with AMPH 14 and 24 days after stress. AAV-BDNF rats exposed to stress showed prolonged cross-sensitization and facilitated sensitization to the second drug challenge. Immunohistochemistry showed that the combination of virally enhanced VTA BDNF, stress, and AMPH resulted in increased ΔFosB in the NAc shell compared with the other groups. Thus, elevation of VTA BDNF prolongs cross-sensitization, facilitates sensitization, and increases ΔFosB in mesocorticolimbic terminal regions. As such, elevated VTA BDNF may be a risk factor for drug sensitivity.

  1. The subthalamic nucleus, Part I

    NARCIS (Netherlands)

    Marani, Enrico; Heida, Tjitske; Lakke, Egbert A.J.F.; Usunoff, Kamen G.

    2008-01-01

    Part I. Development, cytology, topography and connections. This monograph on the subthalamic nucleus accentuates in Part I the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology

  2. Heavy flavors in nucleus-nucleus and proton-nucleus collisions

    Directory of Open Access Journals (Sweden)

    Nardi Marzia

    2016-01-01

    Full Text Available A multi-step setup for heavy-flavor studies in high-energy nucleus-nucleus (AA and proton-nucleus (pA collisions is presented. The propagation of the heavy quarks in the medium is described in a framework provided by the relativistic Langevin equation, here solved using weak-coupling transport coefficients. Successively, the heavy quarks hadronize in the medium. We compute the nuclear modification factor and the elliptic flow parameter of the final Dmesons both in AA and in pA collisions and compare our results to experimental data.

  3. Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking

    OpenAIRE

    Cook, Jason B.; Hendrickson, Linzy M.; Garwood, Grant M.; Toungate, Kelsey M.; Nania, Christina V.; Morikawa, Hitoshi

    2017-01-01

    Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets...

  4. Encoding of aversion by dopamine and the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    James Edgar Mccutcheon

    2012-09-01

    Full Text Available Adaptive motivated behavior requires rapid discrimination between beneficial and harmful stimuli. Such discrimination leads to the generation of either an approach or rejection response, as appropriate, and enables organisms to maximize reward and minimize punishment. Classically, the nucleus accumbens (NAc and the dopamine projection to it are considered an integral part of the brain’s reward circuit, i.e., they direct approach and consumption behaviors and underlie positive reinforcement. This reward-centered framing ignores important evidence about the role of this system in encoding aversive events. One reason for bias towards reward is the difficulty in designing experiments in which animals repeatedly experience punishments; another is the challenge in dissociating the response to an aversive stimulus itself from the reward/relief experienced when an aversive stimulus is terminated. Here, we review studies that employ techniques with sufficient time resolution to measure responses in ventral tegmental area (VTA and NAc to aversive stimuli as they are delivered. We also present novel findings showing that the same stimulus – intraoral infusion of sucrose – has differing effects on NAc shell dopamine release depending on the prior experience. Here, for some rats, sucrose was rendered aversive by explicitly pairing it with malaise in a conditioned taste aversion paradigm. Thereafter, sucrose infusions led to a suppression of dopamine with a similar magnitude and time course to intra-oral infusions of a bitter quinine solution. The results are discussed in the context of regional differences in dopamine signaling and the implications of a pause in phasic dopamine release within the NAc shell. Together with our data, the emerging literature suggests an important role for differential phasic dopamine signaling in aversion versus reward.

  5. Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function.

    Science.gov (United States)

    Vinish, Monika; Elnabawi, Ahmed; Milstein, Jean A; Burke, Jesse S; Kallevang, Jonathan K; Turek, Kevin C; Lansink, Carien S; Merchenthaler, Istvan; Bailey, Aileen M; Kolb, Bryan; Cheer, Joseph F; Frost, Douglas O

    2013-08-01

    Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D₂ receptors; atypical APDs also have multiple serotonergic activities. DA and serotonin regulate many neurodevelopmental processes. Thus, early life APD treatment can, potentially, perturb these processes, causing long-term behavioural and neurobiological sequelae. We treated adolescent, male rats with olanzapine (Ola) on post-natal days 28-49, under dosing conditions that approximate those employed therapeutically in humans. As adults, they exhibited enhanced conditioned place preference for amphetamine, as compared to vehicle-treated rats. In the nucleus accumbens core, DA D₁ receptor binding was reduced, D₂ binding was increased and DA release evoked by electrical stimulation of the ventral tegmental area was reduced. Thus, adolescent Ola treatment enduringly alters a key behavioural response to rewarding stimuli and modifies DAergic neurotransmission in the nucleus accumbens. The persistence of these changes suggests that even limited periods of early life Ola treatment may induce enduring changes in other reward-related behaviours and in behavioural and neurobiological responses to therapeutic and illicit psychotropic drugs. These results underscore the importance of improved understanding of the enduring sequelae of paediatric APD treatment as a basis for weighing the benefits and risks of adolescent APD therapy, especially prophylactic treatment in high-risk, asymptomatic patients.

  6. Cocaine sensitization increases subthreshold activity in dopamine neurons from the ventral tegmental area.

    Science.gov (United States)

    Arencibia-Albite, Francisco; Vázquez-Torres, Rafael; Jiménez-Rivera, Carlos A

    2017-02-01

    The progressive escalation of psychomotor responses that results from repeated cocaine administration is termed sensitization. This phenomenon alters the intrinsic properties of dopamine (DA) neurons from the ventral tegmental area (VTA), leading to enhanced dopaminergic transmission in the mesocorticolimbic network. The mechanisms underlying this augmented excitation are nonetheless poorly understood. DA neurons display the hyperpolarization-activated, nonselective cation current, dubbed Ih We recently demonstrated that Ih and membrane capacitance are substantially reduced in VTA DA cells from cocaine-sensitized rats. The present study shows that 7 days of cocaine withdrawal did not normalize Ih and capacitance. In cells from cocaine-sensitized animals, the amplitude of excitatory synaptic potentials, at -70 mV, was ∼39% larger in contrast to controls. Raise and decay phases of the synaptic signal were faster under cocaine, a result associated with a reduced membrane time constant. Synaptic summation was paradoxically elevated by cocaine exposure, as it consisted of a significantly reduced summation indexed but a considerably increased depolarization. These effects are at least a consequence of the reduced capacitance. Ih attenuation is unlikely to explain such observations, since at -70 mV, no statistical differences exist in Ih or input resistance. The neuronal shrinkage associated with a diminished capacitance may help to understand two fundamental elements of drug addiction: incentive sensitization and negative emotional states. A reduced cell size may lead to substantial enhancement of cue-triggered bursting, which underlies drug craving and reward anticipation, whereas it could also result in DA depletion, as smaller neurons might express low levels of tyrosine hydroxylase. This work uses a new approach that directly extracts important biophysical parameters from alpha function-evoked synaptic potentials. Two of these parameters are the cell membrane

  7. Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of the Ghrelin Receptor in the Ventral Tegmental Area

    DEFF Research Database (Denmark)

    Skov, Louise J; Jensen, Morten; Christiansen, Søren H

    2017-01-01

    Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-R(VTA) mice) to spec......Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-R(VTA) mice...... intake and energy expenditure compared to Ghr-R knockout mice, demonstrating the significance of Ghr-R signaling in the response to stress. Ghr-R(VTA) mice also showed increased cocaine-induced locomotor activity compared to Ghr-R knockout mice, highlighting the importance of ghrelin signaling...

  8. Fast mixing condensation nucleus counter

    OpenAIRE

    Flagan, Richard C.; Wang, Jian

    2003-01-01

    A fast mixing condensation nucleus counter useful for detecting particles entrained in a sample gas stream is provided. The fast mixing condensation nucleus counter comprises a detector and a mixing condensation device having a mixing chamber adapted to allow gas to flow from an inlet to an outlet, wherein the outlet directs the gas flow to the detector. The mixing chamber has an inlet for introducing vapor-laden gas into the chamber and at least one nozzle for introducing a sample gas having...

  9. Functionalized active-nucleus complex sensor

    Science.gov (United States)

    Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

    2003-11-25

    A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

  10. ERK1/2 activation in rat ventral tegmental area by the mu-opioid agonist fentanyl : An in vitro study

    NARCIS (Netherlands)

    Lesscher, HMB; Burbach, JPH; Van Ree, JM; Gerrits, MAFM

    2003-01-01

    Opioid receptors in the ventral tegmental area, predominantly the mu-opioid receptors, have been suggested to modulate reinforcement sensitivity for both opioid and non-opioid drugs of abuse. The present study was conducted to study signal transduction proteins, which may mediate the functioning of

  11. Heavy-ion nucleus scattering

    CERN Document Server

    Rahman, M A; Haque, S

    2003-01-01

    Heavy ion-nucleus scattering is an excellent laboratory to probe high spin phenomena, exotic nuclei and for the analysis of various exit channels. The Strong Absorption Model or the generalized diffraction models, which are semi-classical in nature, have been employed in the description of various heavy ion-nucleus scattering phenomena with reasonable success. But one needs to treat the deflection function (scattering angles) quantum mechanically in the Wave Mechanical picture for the appropriate description of the heavy-ion nucleus scattering phenomena. We have brought the mathematics for the cross-section of the heavy-ion nucleus scattering to an analytic expression taking account of the deflection function (scattering angles) quantum mechanically. sup 9 Be, sup 1 sup 6 O, sup 2 sup 0 Ne and sup 3 sup 2 S heavy-ion beams elastic scattering from sup 2 sup 8 Si, sup 2 sup 4 Mg and sup 4 sup 0 Ca target nuclei at various projectile energies over the range 20-151 MeV have been analysed in terms of the 2-paramet...

  12. Targeting corticotropin-releasing factor (CRF) projections from the oval nucleus of the BNST using cell-type specific neuronal tracing studies in mouse and rat brain

    Science.gov (United States)

    Dabrowska, Joanna; Martinon, Daisy; Moaddab, Mahsa; Rainnie, Donald G.

    2016-01-01

    The bed nucleus of the stria terminalis (BNST) is known to play a critical role in mediating the behavioral and autonomic responses to stressors. The oval nucleus of the BNST (BNSTov) contains cell bodies that synthesize the stress hormone, corticotropin releasing factor (CRF). Although afferent fibers originating from the BNSTov have been shown to innervate several key structures of the neuroendocrine and central autonomic system, the question remains as to whether, some of these fibers are CRF-positive. To directly address this question, we injected a “floxed” anterograde tracer (rAAV5/EF1a-DIO-mCherry) into the BNSTov of CRFp3.0CreGFP transgenic mice, which express a green fluorescent protein (GFP) under the control of the CRF promoter. Serial sections were then analyzed for the presence of double-labeled fibers in potential projection sites. To determine whether CRF neurons in the rat BNSTov send comparable projections, we infused rat BNSTov with an AAV in which the human synapsin promoter drives enhanced GFP expression. We then used CRF immunoreactivity to examine double-labeled fluorescent fibers and axon terminals in projection sites from brain sections of the AAV-infused rats. We have observed several terminal fields in the mouse and rat brain with double-labeled fibers in the Dorsal raphe nucleus (DRD), the Paraventricular nucleus of the hypothalamus, and to a lesser extent in the Ventral tegmental area. We found double-labeled terminal boutons in the nucleus accumbens shell, prelimbic cortex, and posterior basolateral nucleus of the amygdala. The most intense double-labeling was found in midbrain, including substantia nigra pars compacta, red nucleus, periaqueductal gray, pontine nuclei, as well as DRD. The results of our study indicate that CRF neurons are the output neurons of the BNSTov and they send projections to the centers of neuroendocrine and autonomic regulation, but also regions modulating reward and motivation, vigilance, motor function

  13. CRF neurons in the ventral tegmental area control the aversive effects of nicotine withdrawal and promote escalation of nicotine intake

    Science.gov (United States)

    Grieder, Taryn E.; Herman, Melissa A.; Contet, Candice; Tan, Laura A.; Vargas-Perez, Hector; Cohen, Ami; Chwalek, Michal; Maal-Bared, Geith; Freiling, John; Schlosburg, Joel E; Clarke, Laura; Crawford, Elena; Koebel, Pascale; Canonigo, Vez; Sanna, Pietro; Tapper, Andrew; Roberto, Marisa; Kieffer, Brigitte L.; Sawchenko, Paul E.; Koob, George F.; van der Kooy, Derek; George, Olivier

    2014-01-01

    SUMMARY Dopaminergic neurons in the ventral tegmental area (VTA) are well known for their role in mediating the positive reinforcing effects of drugs of abuse. Here, we identify in rodents and humans a population of VTA dopamine neurons co-expressing corticotropin releasing factor (CRF). We provide further evidence in rodents that chronic nicotine exposure upregulates CRF mRNA in dopaminergic neurons of the posterior VTA, activates local CRF1 receptors, and blocks nicotine-induced activation of transient GABAergic input to dopaminergic neurons. Local downregulation of CRF mRNA and specific pharmacological blockade of CRF1 receptors in the VTA reversed the effect of nicotine on GABAergic input to dopaminergic neurons, prevented the aversive effects of nicotine withdrawal, and limited the escalation of nicotine intake. These results link the brain reward and stress systems within the same brain region in signaling the negative motivational effects of nicotine withdrawal. PMID:25402857

  14. Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral tegmental area in vitro

    DEFF Research Database (Denmark)

    Rice, M E; Richards, C D; Nedergaard, S

    1994-01-01

    Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous...... electrophysiological studies have demonstrated that cells of the caudal SN and the VTA have similar characteristics, whereas cells in the rostral SN have distinctly different properties. In the present study, we confirmed that each region has tyrosine hydroxylase-positive neurons and determined, using high......-HT. Release signals were monitored every 250 ms with a spatial resolution of less than 50 microns.l DA release was calcium-dependent and was not detectable in a catecholamine-poor area such as the cerebellum, or in mid-brain tissue pre-treated with reserpine. Within the normal mid-brain, the amount...

  15. Striatal and Tegmental Neurons Code Critical Signals for Temporal-Difference Learning of State Value in Domestic Chicks.

    Science.gov (United States)

    Wen, Chentao; Ogura, Yukiko; Matsushima, Toshiya

    2016-01-01

    To ensure survival, animals must update the internal representations of their environment in a trial-and-error fashion. Psychological studies of associative learning and neurophysiological analyses of dopaminergic neurons have suggested that this updating process involves the temporal-difference (TD) method in the basal ganglia network. However, the way in which the component variables of the TD method are implemented at the neuronal level is unclear. To investigate the underlying neural mechanisms, we trained domestic chicks to associate color cues with food rewards. We recorded neuronal activities from the medial striatum or tegmentum in a freely behaving condition and examined how reward omission changed neuronal firing. To compare neuronal activities with the signals assumed in the TD method, we simulated the behavioral task in the form of a finite sequence composed of discrete steps of time. The three signals assumed in the simulated task were the prediction signal, the target signal for updating, and the TD-error signal. In both the medial striatum and tegmentum, the majority of recorded neurons were categorized into three types according to their fitness for three models, though these neurons tended to form a continuum spectrum without distinct differences in the firing rate. Specifically, two types of striatal neurons successfully mimicked the target signal and the prediction signal. A linear summation of these two types of striatum neurons was a good fit for the activity of one type of tegmental neurons mimicking the TD-error signal. The present study thus demonstrates that the striatum and tegmentum can convey the signals critically required for the TD method. Based on the theoretical and neurophysiological studies, together with tract-tracing data, we propose a novel model to explain how the convergence of signals represented in the striatum could lead to the computation of TD error in tegmental dopaminergic neurons.

  16. Striatal and Tegmental Neurons Code Critical Signals for Temporal-Difference Learning of State Value in Domestic Chicks

    Directory of Open Access Journals (Sweden)

    Chentao Wen

    2016-11-01

    Full Text Available To ensure survival, animals must update the internal representations of their environment in a trial-and-error fashion. Psychological studies of associative learning and neurophysiological analyses of dopaminergic neurons have suggested that this updating process involves the temporal-difference (TD method in the basal ganglia network. However, the way in which the component variables of the TD method are implemented at the neuronal level is unclear. To investigate the underlying neural mechanisms, we trained domestic chicks to associate color cues with food rewards. We recorded neuronal activities from the medial striatum or tegmentum in a freely behaving condition and examined how reward omission changed neuronal firing. To compare neuronal activities with the signals assumed in the TD method, we simulated the behavioral task in the form of a finite sequence composed of discrete steps of time. The three signals assumed in the simulated task were the prediction signal, the target signal for updating, and the TD-error signal. In both the medial striatum and tegmentum, the majority of recorded neurons were categorized into three types according to their fitness for three models, though these neurons tended to form a continuum spectrum without distinct differences in the firing rate. Specifically, two types of striatal neurons successfully mimicked the target signal and the prediction signal. A linear summation of these two types of striatum neurons was a good fit for the activity of one type of tegmental neurons mimicking the TD-error signal. The present study thus demonstrates that the striatum and tegmentum can convey the signals critically required for the TD method. Based on the theoretical and neurophysiological studies, together with tract-tracing data, we propose a novel model to explain how the convergence of signals represented in the striatum could lead to the computation of TD error in tegmental dopaminergic neurons.

  17. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

    Science.gov (United States)

    Cook, Jason B; Werner, David F; Maldonado-Devincci, Antoniette M; Leonard, Maggie N; Fisher, Kristen R; O'Buckley, Todd K; Porcu, Patrizia; McCown, Thomas J; Besheer, Joyce; Hodge, Clyde W; Morrow, A Leslie

    2014-04-23

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

  18. Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

    Directory of Open Access Journals (Sweden)

    David eDARDOU

    2015-01-01

    Full Text Available The loss of dopamine neurons observed in Parkinson’s disease (PD elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the dopamine 3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long term stimulation of the dopamine 3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.

  19. Targeting Corticotropin-Releasing Factor Projections from the Oval Nucleus of the Bed Nucleus of the Stria Terminalis Using Cell-Type Specific Neuronal Tracing Studies in Mouse and Rat Brain.

    Science.gov (United States)

    Dabrowska, J; Martinon, D; Moaddab, M; Rainnie, D G

    2016-12-01

    The bed nucleus of the stria terminalis (BNST) is known to play a critical role in mediating the behavioural and autonomic responses to stressors. The oval nucleus of the BNST (BNSTov) contains cell bodies that synthesise the stress hormone corticotropin-releasing factor (CRF). Although afferent fibres originating from the BNSTov have been shown to innervate several key structures of the neuroendocrine and central autonomic system, the question remains as to whether some of these fibres are CRF-positive. To directly address this question, we injected a 'floxed' anterograde tracer (rAAV5/EF1a-DIO-mCherry) into the BNSTov of CRFp3.0CreGFP transgenic mice, which express a green fluorescent protein (GFP) under the control of the CRF promoter. Serial sections were then analysed for the presence of double-labelled fibres in potential projection sites. To determine whether CRF neurons in the rat BNSTov send comparable projections, we infused rat BNSTov with an adeno-associated viral vector (AAV) in which the human synapsin promoter drives enhanced GFP expression. We then used CRF immunoreactivity to examine double-labelled fluorescent fibres and axon terminals in projection sites from brain sections of the AAV-infused rats. We have observed several terminal fields in the mouse and rat brain with double-labelled fibres in the Dorsal raphe nucleus (DRD), the paraventricular nucleus of the hypothalamus and, to a lesser extent, in the ventral tegmental area. We found double-labelled terminal boutons in the nucleus accumbens shell, prelimbic cortex and posterior basolateral nucleus of the amygdala. The most intense double-labelling was found in midbrain, including substantia nigra pars compacta, red nucleus, periaqueductal grey and pontine nuclei, as well as DRD. The results of the present study indicate that CRF neurons are the output neurons of the BNSTov and they send projections not only to the centres of neuroendocrine and autonomic regulation, but also regions modulating

  20. Absence of jet quenching in peripheral nucleus-nucleus collisions

    Science.gov (United States)

    Loizides, Constantin; Morsch, Andreas

    2017-10-01

    Medium effects on the production of high-pT particles in nucleus-nucleus (AA) collisions are generally quantified by the nuclear modification factor (RAA), defined to be unity in absence of nuclear effects. Modeling particle production including a nucleon-nucleon impact parameter dependence, we demonstrate that RAA at midrapidity in peripheral AA collisions can be significantly affected by event selection and geometry biases. Even without jet quenching and shadowing, these biases cause an apparent suppression for RAA in peripheral collisions, and are relevant for all types of hard probes and all collision energies. Our studies indicate that calculations of jet quenching in peripheral AA collisions should account for the biases, or else they will overestimate the relevance of parton energy loss. Similarly, expectations of parton energy loss in light-heavy collision systems based on comparison with apparent suppression seen in peripheral RAA should be revised. Our interpretation of the peripheral RAA data would unify observations for lighter collision systems or lower energies where significant values of elliptic flow are observed despite the absence of strong jet quenching.

  1. Repeated toluene exposure increases c-Fos in catecholaminergic cells of the nucleus accumbens shell.

    Science.gov (United States)

    Tomaszycki, Michelle L; Aulerich, Kelsey E; Bowen, Scott E

    2013-01-01

    Toluene is a frequently abused solvent. Previous studies have suggested that toluene acts like other drugs of abuse, specifically on the dopaminergic system in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the mesolimbic pathway. Although changes in dopamine (DA) levels and c-Fos have been observed in both acute and repeated exposure paradigms, the extent to which c-Fos is localized to catecholaminergic cells is unknown. The present study tested the effects of repeated toluene exposure (1000-4000ppm) on locomotor activity and cells containing c-Fos, tyrosine hydroxylase (TH), or both in the core and shell of the NAc, as well as the anterior and posterior VTA. We focused our study on adolescents, since adolescence is a time of great neural change and a time when individuals tend to be more susceptible to drug abuse. In early tests, toluene dose-dependently increased locomotor activity. Repeated exposure to the highest concentration of toluene resulted in sensitization to toluene's effects on locomotor activity. Although the number of cells immunopositive for c-Fos or TH did not significantly differ across groups, cells immunopositive for TH+c-Fos were higher in the NAc shell of animals exposed to 4000ppm than in animals exposed to air (control) or 1000ppm. Taken together, these findings demonstrate that repeated high dose toluene exposure increases locomotor activity as well as activation of catecholaminergic cells in the shell of the NAc. © 2013 Elsevier Inc. All rights reserved.

  2. Activation in the VTA and nucleus accumbens increases in anticipation of both gains and losses

    Directory of Open Access Journals (Sweden)

    R. McKell Carter

    2009-08-01

    Full Text Available To represent value for learning and decision making, the brain must encode information about both the motivational relevance and affective valence of anticipated outcomes. The nucleus accumbens (NAcc and ventral tegmental area (VTA are thought to play key roles in representing these and other aspects of valuation. Here, we manipulated the valence (i.e., monetary gain or loss and personal relevance (i.e., self-directed or charity-directed of anticipated outcomes within a variant of the monetary incentive delay task (MID. We scanned young-adult participants using functional magnetic resonance imaging (fMRI, utilizing imaging parameters targeted for the NAcc and VTA. For both self-directed and charity-directed trials, activation in the NAcc and VTA increased to anticipated gains, as predicted by prior work, but also increased to anticipated losses. Moreover, the magnitude of responses in both regions was positively correlated for gains and losses, across participants, while an independent reward-sensitivity covariate predicted the relative difference between and gain- and loss-related activation on self-directed trials. These results are inconsistent with the interpretation that these regions reflect anticipation of only positive-valence events. Instead, they indicate that anticipatory activation in reward-related regions largely reflects the motivational relevance of an upcoming event.

  3. MORPHINE PRODUCES CIRCUIT-SPECIFIC NEUROPLASTICITY IN THE BED NUCLEUS OF THE STRIA TERMINALIS

    Science.gov (United States)

    Dumont, É. C.; Rycroft, B. K.; Maiz, J.; Williams, J. T.

    2013-01-01

    The bed nucleus of the stria terminalis (BST) is a brain structure located at the interface of the cortex and the cerebrospinal trunk. The BST is a cluster of nuclei organized in a complex intrinsic network that receives inputs from cortical and subcortical sources, and that sends a widespread top-down projection. There is growing evidence that the BST is a key component in the neurobiological basis of substance abuse. In the present study, the regulation of excitatory inputs onto identified neurons in the BST was examined in rats treated chronically with morphine. Neurons projecting to the ventral tegmental area (VTA) were identified by retrograde transport of fluorescent microspheres and recorded in the whole-cell voltage clamp configuration in brain slices. Selective excitatory inputs to these neurons were electrically evoked with electrodes placed in the medial and lateral aspects of the dorsal BST. The chronic morphine treatment selectively increased AMPA-dependent excitatory postsynaptic currents in a subset of inputs activated by dorso-lateral stimulation in the BST. Inputs activated by medial stimulation were not affected by morphine. Likewise, the inputs to neurons that did not project to the VTA were not changed by morphine. Altogether, these results extend the understanding of neuronal circuits intrinsically sensitive to drugs of abuse within the BST. PMID:18343592

  4. A preoperative metabolic marker of parkinsonian apathy following subthalamic nucleus stimulation.

    Science.gov (United States)

    Gesquière-Dando, Aude; Guedj, Eric; Loundou, Anderson; Carron, Romain; Witjas, Tatiana; Fluchère, Frédérique; Delfini, Marie; Mundler, Laura; Regis, Jean; Azulay, Jean-Philippe; Eusebio, Alexandre

    2015-11-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) has been associated with the development of postoperative apathy. Debate on the causes of postoperative apathy continues, and the dominant hypothesis is that stimulation or dopaminergic drug reductions are causal in its development. We hypothesized that a preoperative predisposition to apathy also could exist. To this end, we sought to identify a preoperative metabolic pattern using [(18)]Fluorodeoxyglucose Positron Emission Tomography (PET), which could be associated with the occurrence of postoperative apathy after STN-DBS for PD. Thirty-four patients with PD, not clinically apathetic, underwent an [(18)]Fluorodeoxyglucose-PET scan before surgery of STN-DBS, and were tested for the occurrence of apathy 1 y after surgery. Whole-brain voxel-based PET intergroup comparison (P apathy at 1 y and those who did not. Eight patients (23.5%) became apathetic after surgery. Motor improvement and decrease in dopaminergic treatment were similar in both postoperative apathy and non-apathy groups. We found a cluster of significantly greater metabolism in the postoperative apathy group within the cerebellum, brainstem (in particular ventral tegmental area), temporal lobe, insula, amygdala, lentiform nucleus, subgenual anterior cingulate, and inferior frontal gyrus. A metabolic value above 68 could discriminate patients who would develop postoperative apathy with 100% sensitivity and 88.5% specificity. We describe a preoperative metabolic pattern associated with the development of apathy after STN-DBS in PD. This suggests the existence of a predisposition to apathy, which may further be triggered by perioperative drug modifications. © 2015 International Parkinson and Movement Disorder Society.

  5. Kappa opioid receptor activation potentiates the cocaine-induced increase in evoked dopamine release recorded in vivo in the mouse nucleus accumbens.

    Science.gov (United States)

    Ehrich, Jonathan M; Phillips, Paul E M; Chavkin, Charles

    2014-12-01

    Behavioral stressors increase addiction risk in humans and increase the rewarding valence of drugs of abuse including cocaine, nicotine and ethanol in animal models. Prior studies have established that this potentiation of drug reward was mediated by stress-induced release of the endogenous dynorphin opioids and subsequent kappa opioid receptor (KOR) activation. In this study, we used in vivo fast scan cyclic voltammetry to test the hypothesis that KOR activation before cocaine administration might potentiate the evoked release of dopamine from ventral tegmental (VTA) synaptic inputs to the nucleus accumbens (NAc) and thereby increase the rewarding valence of cocaine. The KOR agonist U50488 inhibited dopamine release evoked by either medial forebrain bundle (MFB) or pedunculopontine tegmental nucleus (PPTg) activation of VTA inputs to the shell or core of the mouse NAc. Cocaine administration increased the dopamine response recorded in either the shell or core evoked by either MFB or PPTg stimulation. Administration of U50488 15 min before cocaine blocked the conditioned place preference (CPP) to cocaine, but only significantly reduced the effect of cocaine on the dopamine response evoked by PPTg stimulation to NAc core. In contrast, administration of U50488 60 min before cocaine significantly potentiated cocaine CPP and significantly increased the effects of cocaine on the dopamine response evoked by either MFB or PPTg stimulation, recorded in either NAc shell or core. Results of this study support the concept that stress-induced activation of KOR by endogenous dynorphin opioids may enhance the rewarding valence of drugs of abuse by potentiating the evoked dopamine response.

  6. Determination of Coil Inductances Cylindrical Iron Nucleus

    Directory of Open Access Journals (Sweden)

    Azeddine Mazouz

    2014-03-01

    Full Text Available The paper describes the investigation and development of a structure and performance characteristics of a coil iron nucleus cylindrical (C.I.N.C. The coil iron nucleus cylindrical is a nonlinear electro radio in which the moving of the nucleus in a sense or in other causes change in inductance and can reach extreme values at the superposition of nucleus and coil centers. The variation of the inductance and the degree of freedom of movement of the nucleus can lead to a device with electromechanical conversion The aim of this paper is the determination and visualization of self inductance and mutual of the (C.I.N.C based on geometric dimensions and the displacement of the nucleus.  

  7. A comparative neuroanatomical study of the red nucleus of the cat, macaque and human.

    Directory of Open Access Journals (Sweden)

    Satoru Onodera

    Full Text Available BACKGROUND: The human red nucleus (Nr is comparatively less well-studied than that of cats or monkeys. Given the functional importance of reticular and midbrain structures in control of movement and locomotion as well as from an evolutionary perspective, we investigated the nature and extent of any differences in Nr projections to the olivary complex in quadrupedal and bipedal species. Using neuroanatomical tract-tracing techniques we developed a "neural sheet" hypothesis allowing us to propose how rubro-olivary relations differ among the three species. METHODS AND FINDINGS: Wheat germ agglutinin-horseradish peroxidase staining supports findings that the cat's nucleus accessories medialis of Bechtrew (NB projects mainly to the lateral bend of the principal olive. We clarified boundaries among nucleus of Darkschewitsch (ND, NB and parvicellular red nucleus (pNr of the cat's neural sheet. The macaque's ND-medial accessory olivary projection is rostro-caudally organized and the dorsomedial and ventrolateral parts of the macaque's pNr may project to the principal olive's rostral and caudal dorsal lamella; in cat it projects as well to pNr. Myelin- and Nissl-stained sections show that a well-developed dorsomedial part of the human Nr consists of densely packed cells, deriving small myelinated fibers that continue into the medial central tegmental tract. CONCLUSIONS: Based on these findings we suggest there are distinct bipedal-quadrupedal differences for Nr projections to the olivary complex. We propose the Nr of cats and monkeys comprise the ND, NB and pNr in a zonal sheet-like structure, retaining clear nuclear boundaries and an isolated, well-developed mNr. The human NB may be distinguished from its more specialised ND (ND lies alongside a well-developed pNr in the human central gray. Phylogenetically, the NB may have been translocated into a roll-shaped Nr in the reticular formation, the dorsomedial portion of which might correspond to the cat

  8. Inhibitory effect of NMDA receptors in the ventral tegmental area on hormonal and eating behavior responses to stress in rats.

    Science.gov (United States)

    Nasihatkon, Zohreh Sadat; Khosravi, Maryam; Bourbour, Zahra; Sahraei, Hedayat; Ranjbaran, Mina; Hassantash, Seyedeh Maryam; Sahraei, Mohammad; Baghlani, Kefayat

    2014-01-01

    Stress and its consequences are among the causes of accidents. The effects of intraventral tegmental area (I-VTA) memantine on the plasma corticosterone and eating parameters disturbance induced by acute stress were investigated. Male Wistar rats (W: 250-300 g) were divided into control and experiential groups, each of which received memantine either intra-VTA or peripherally. One week after bilateral cannulation, the rats received memantine (1 and 5 μg/Rat) five min before electroshock stress. The other experimental groups received memantine (1 and 5 mg/kg) intraperitoneally 30 min before stress. The control groups received saline or memantine but did not experience stress. Food and water intake and plasma corticosterone level were recorded. Results showed that stress decreases food intake but does not change water intake and increase in plasma corticosterone level. Intraperitoneal memantine administration slightly inhibits the stress effects on food intake. However, water intake and plasma corticosterone level were increased. Intra-VTA memantine reduces the effects of stress on corticosterone and water intake. It could be concluded that inhibition of glutamate NMDA receptors in the VTA by memantine leads to the inhibition of the eating behavior parameters and plasma corticosterone level disturbance induced by stress in rats.

  9. Role for mTOR signaling and neuronal activity in morphine-induced adaptations in ventral tegmental area dopamine neurons.

    Science.gov (United States)

    Mazei-Robison, Michelle S; Koo, Ja Wook; Friedman, Allyson K; Lansink, Carien S; Robison, Alfred J; Vinish, Monika; Krishnan, Vaishnav; Kim, Seyun; Siuta, Michael A; Galli, Aurelio; Niswender, Kevin D; Appasani, Raghu; Horvath, Monika C; Neve, Rachel L; Worley, Paul F; Snyder, Solomon H; Hurd, Yasmin L; Cheer, Joseph F; Han, Ming-Hu; Russo, Scott J; Nestler, Eric J

    2011-12-22

    While the abuse of opiate drugs continues to rise, the neuroadaptations that occur with long-term drug exposure remain poorly understood. We describe here a series of chronic morphine-induced adaptations in ventral tegmental area (VTA) dopamine neurons, which are mediated via downregulation of AKT-mTORC2 (mammalian target of rapamycin complex-2). Chronic opiates decrease the size of VTA dopamine neurons in rodents, an effect seen in humans as well, and concomitantly increase the excitability of the cells but decrease dopamine output to target regions. Chronic morphine decreases mTORC2 activity, and overexpression of Rictor, a component of mTORC2, prevents morphine-induced changes in cell morphology and activity. Further, local knockout of Rictor in VTA decreases DA soma size and reduces rewarding responses to morphine, consistent with the hypothesis that these adaptations represent a mechanism of reward tolerance. Together, these findings demonstrate a novel role for AKT-mTORC2 signaling in mediating neuroadaptations to opiate drugs of abuse. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Human substantia nigra and ventral tegmental area involvement in computing social error signals during the ultimatum game.

    Science.gov (United States)

    Hétu, Sébastien; Luo, Yi; D'Ardenne, Kimberlee; Lohrenz, Terry; Montague, P Read

    2017-12-01

    As models of shared expectations, social norms play an essential role in our societies. Since our social environment is changing constantly, our internal models of it also need to change. In humans, there is mounting evidence that neural structures such as the insula and the ventral striatum are involved in detecting norm violation and updating internal models. However, because of methodological challenges, little is known about the possible involvement of midbrain structures in detecting norm violation and updating internal models of our norms. Here, we used high-resolution cardiac-gated functional magnetic resonance imaging and a norm adaptation paradigm in healthy adults to investigate the role of the substantia nigra/ventral tegmental area (SN/VTA) complex in tracking signals related to norm violation that can be used to update internal norms. We show that the SN/VTA codes for the norm's variance prediction error (PE) and norm PE with spatially distinct regions coding for negative and positive norm PE. These results point to a common role played by the SN/VTA complex in supporting both simple reward-based and social decision making. © The Author (2017). Published by Oxford University Press.

  11. Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat.

    Science.gov (United States)

    Li, Ai-Ling; Sibi, Jiny E; Yang, Xiaofei; Chiao, Jung-Chih; Peng, Yuan Bo

    2016-06-01

    Deep brain stimulation has been found to be effective in relieving intractable pain. The ventral tegmental area (VTA) plays a role not only in the reward process, but also in the modulation of nociception. Lesions of VTA result in increased pain thresholds and exacerbate pain in several pain models. It is hypothesized that direct activation of VTA will reduce pain experience. In this study, we investigated the effect of direct electrical stimulation of the VTA on mechanical, thermal and carrageenan-induced chemical nociceptive thresholds in Sprague-Dawley rats using our custom-designed wireless stimulator. We found that: (1) VTA stimulation itself did not show any change in mechanical or thermal threshold; and (2) the decreased mechanical and thermal thresholds induced by carrageenan injection in the hind paw contralateral to the stimulation site were significantly reversed by VTA stimulation. To further explore the underlying mechanism of VTA stimulation-induced analgesia, spinal cord dorsal horn neuronal responses to graded mechanical stimuli were recorded. VTA stimulation significantly inhibited dorsal horn neuronal activity in response to pressure and pinch from the paw, but not brush. This indicated that VTA stimulation may have exerted its analgesic effect via descending modulatory pain pathways, possibly through its connections with brain stem structures and cerebral cortex areas.

  12. Contingent and non-contingent effects of low-dose ethanol on GABA neuron activity in the ventral tegmental area

    Science.gov (United States)

    Steffensen, Scott C.; Walton, Christine H.; Hansen, David M.; Yorgason, Jordan T.; Gallegos, Roger A.; Criado, Jose R.

    2010-01-01

    Ventral tegmental area (VTA) GABA neurons appear to be critical regulators of mesocorticolimbic dopamine (DA) neurotransmission, which has been implicated in alcohol reward. The aim of this study was to evaluate the effects of low-dose “non-contingent” intravenous (IV) ethanol (0.01–0.1 g/kg) on VTA GABA neuron firing rate and synaptic responses, as well as VTA GABA neuron firing rate during low-dose “contingent” IV ethanol self-administration. Intravenous administration of 0.01–0.03 g/kg ethanol significantly increased VTA GABA neuron firing rate and afferent-evoked synaptic responses. In the runway self-administration paradigm, presentation of an olfactory cue (S+; almond extract) or no-cue (S−; no odor) in the Start box was paired with IV administration of low-dose ethanol (0.01 g/kg) or saline in the Target box. Runway excursion times decreased significantly in association during S+, and increased significantly during S− conditions. The firing rate of VTA GABA neurons markedly increased when rats received 0.01 g/kg IV ethanol in the Target box. VTA GABA neuron firing increased in the Start box of the runway in association with S+, but not S−. These findings demonstrate that VTA GABA neurons are activated by low-dose IV ethanol and that their firing rate increases in anticipation of ethanol reward. PMID:18996142

  13. Sox6 and Otx2 Control the Specification of Substantia Nigra and Ventral Tegmental Area Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    Lia Panman

    2014-08-01

    Full Text Available Distinct midbrain dopamine (mDA neuron subtypes are found in the substantia nigra pars compacta (SNc and the ventral tegmental area (VTA, but it is mainly SNc neurons that degenerate in Parkinson’s disease. Interest in how mDA neurons develop has been stimulated by the potential use of stem cells in therapy or disease modeling. However, very little is known about how specific dopaminergic subtypes are generated. Here, we show that the expression profiles of the transcription factors Sox6, Otx2, and Nolz1 define subpopulations of mDA neurons already at the neural progenitor cell stage. After cell-cycle exit, Sox6 selectively localizes to SNc neurons, while Otx2 and Nolz1 are expressed in a subset of VTA neurons. Importantly, Sox6 ablation leads to decreased expression of SNc markers and a corresponding increase in VTA markers, while Otx2 ablation has the opposite effect. Moreover, deletion of Sox6 affects striatal innervation and dopamine levels. We also find reduced Sox6 levels in Parkinson’s disease patients. These findings identify Sox6 as a determinant of SNc neuron development and should facilitate the engineering of relevant mDA neurons for cell therapy and disease modeling.

  14. Hadron-nucleus bound states

    CERN Document Server

    Yamazaki, T

    2000-01-01

    A new type of nuclear spectroscopy to study hadron-nucleus bound states is described. The first successful experiment was to search for deeply bound pi sup - states in heavy nuclei using the sup 2 sup 0 sup 8 Pb(d, sup 3 He) reaction at GSI, in which a narrow peak arising from the 2p pi sup - orbital coupled with the neutron-hole states was observed at 135 MeV excitation energy. An improved experiment has just been carried out to separately identify the 1s and 2p pi sup - states. These experiments provide important information on the local potential strength, from which the effective mass of pi sup - is deduced to be 20 MeV. This method will be extended to search for eta and omega bound states as well as for K sup - bound states. The advantage of the bound-state spectroscopy versus invariant mass spectroscopy is emphasized.

  15. Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia.

    Directory of Open Access Journals (Sweden)

    Martina Krenzer

    Full Text Available Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM sleep.To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2 or vesicular GABA-glycine transporter (VGAT genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG and lateral pontine tegmentum (LPT are not critically involved in REM sleep control.These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD.

  16. Action potentials: to the nucleus and beyond.

    Science.gov (United States)

    Saha, Ramendra N; Dudek, Serena M

    2008-04-01

    The neuronal nucleus is now widely accepted as playing a vital role in maintaining long-term changes in synaptic effectiveness. To act, however, the nucleus must be appropriately relayed with information regarding the latest round of synaptic plasticity. Several constraints of doing so in a neuron pertain to the often significant spatial distance of synapses from the nucleus and the number of synapses required for such a signal to reach functional levels in the nucleus. Largely based on the sensitivity of transcriptional responses to NMDA receptor antagonists, it has been postulated that the signals are physically relayed by biochemical messengers from the synapse to the nucleus. Alternatively, a second, less often considered but equally viable method of signal transduction may be initiated by action potentials generated proximal to the nucleus, wherefrom the signal can be relayed directly by calcium or indirectly by biochemical second messengers. We consider action potential-dependent signaling to the nucleus to have its own computational advantages over the synapse-to-nucleus signal for some functions. This minireview summarizes the logic and experimental support for these two modes of signaling and attempts to validate the action potential model as playing an important role in transcriptional regulation relating specifically to long-term synaptic plasticity.

  17. Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine.

    Science.gov (United States)

    Gomez-A, Alexander; Fiorenza, Amanda M; Boschen, Suelen L; Sugi, Adam H; Beckman, Danielle; Ferreira, Sergio T; Lee, Kendall; Blaha, Charles D; Da Cunha, Claudio

    2017-02-15

    Diazepam is a benzodiazepine receptor agonist with anxiolytic and addictive properties. Although most drugs of abuse increase the level of release of dopamine in the nucleus accumbens, here we show that diazepam not only causes the opposite effect but also prevents amphetamine from enhancing dopamine release. We used 20 min sampling in vivo microdialysis and subsecond fast-scan cyclic voltammetry recordings at carbon-fiber microelectrodes to show that diazepam caused a dose-dependent decrease in the level of tonic and electrically evoked dopamine release in the nucleus accumbens of urethane-anesthetized adult male Swiss mice. In fast-scan cyclic voltammetry assays, dopamine release was evoked by electrical stimulation of the ventral tegmental area. We observed that 2 and 3 mg of diazepam/kg reduced the level of electrically evoked dopamine release, and this effect was reversed by administration of the benzodiazepine receptor antagonist flumazenil in doses of 2.5 and 5 mg/kg, respectively. No significant effects on measures of dopamine re-uptake were observed. Cyclic voltammetry experiments further showed that amphetamine (5 mg/kg, intraperitoneally) caused a significant increase in the level of dopamine release and in the half-life for dopamine re-uptake. Diazepam (2 mg/kg) significantly weakened the effect of amphetamine on dopamine release without affecting dopamine re-uptake. These results suggest that the pharmacological effects of benzodiazepines have a dopaminergic component. In addition, our findings challenge the classic view that all drugs of abuse cause dopamine release in the nucleus accumbens and suggest that benzodiazepines could be useful in the treatment of addiction to other drugs that increase the level of dopamine release, such as cocaine, amphetamines, and nicotine.

  18. Regional influence of cocaine on evoked dopamine release in the nucleus accumbens core: A role for the caudal brainstem.

    Science.gov (United States)

    Gerth, Ashlynn I; Alhadeff, Amber L; Grill, Harvey J; Roitman, Mitchell F

    2017-01-15

    Cocaine increases dopamine concentration in the nucleus accumbens through competitive binding to the dopamine transporter (DAT). However, it also increases the frequency of dopamine release events, a finding that cannot be explained by action at the DAT alone. Rather, this effect may be mediated by cocaine-induced modulation of brain regions that project to dopamine neurons. To explore regional contributions of cocaine to dopamine signaling, we administered cocaine to the lateral or fourth ventricles and compared the effects on dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area to that of systemically-delivered cocaine. Stimulation trains caused a sharp rise in dopamine followed by a slower return to baseline. The magnitude of dopamine release ([DA]max) as well as the latency to decay to fifty percent of the maximum (t(1/2); index of DAT activity) by each stimulation train were recorded. All routes of cocaine delivery caused an increase in [DA]max; only systemic cocaine caused an increase in t(1/2). Importantly, these data are the first to show that hindbrain (fourth ventricle)-delivered cocaine modulates phasic dopamine signaling. Fourth ventricular cocaine robustly increased cFos immunoreactivity in the nucleus of the solitary tract (NTS), suggesting a neural substrate for hindbrain cocaine-mediated effects on [DA]max. Together, the data demonstrate that cocaine-induced effects on phasic dopamine signaling are mediated via actions throughout the brain including the hindbrain. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Phasic excitation of ventral tegmental dopamine neurons potentiates the initiation of conditioned approach behavior: Parametric and reinforcement-schedule analyses

    Directory of Open Access Journals (Sweden)

    Anton eIlango

    2014-05-01

    Full Text Available Midbrain dopamine neurons are implicated in motivation and learning. However, it is unclear how phasic excitation of dopamine neurons, which is implicated in learning, is involved in motivation. Here we used a self-stimulation procedure to examine how mice seek for optogenetically-induced phasic excitation of dopamine neurons, with an emphasis on the temporal dimension. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin-2 into the ventral tegmental area, resulting in selective expression of the opsin in dopamine neurons. These mice were trained to press on a lever for photo-pulse trains that phasically excited dopamine neurons. They learned to self-stimulate in a fast, constant manner, and rapidly reduced pressing during extinction. We first determined effective parameters of photo-pulse trains in self-stimulation. Lever-press rates changed as a function of the manipulation of pulse number, duration, intensity and frequency. We then examined effects of interval and ratio schedules of reinforcement on photo-pulse train reinforcement, which was contrasted with food reinforcement. Reinforcement with food inhibited lever pressing for a few seconds, after which pressing was robustly regulated in a goal-directed manner. In contrast, phasic excitation of dopamine neurons robustly potentiated the initiation of lever pressing; however, this effect did not last more than 1 s and quickly diminished. Indeed, response rates markedly decreased when lever pressing was reinforced with inter-reinforcement interval schedules of 3 or 10 s or ratio schedules requiring multiple responses per reinforcement. Thus, phasic excitation of dopamine neurons briefly potentiates the initiation of approach behavior with apparent lack of long-term motivational regulation.

  20. Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

    Science.gov (United States)

    Cook, Jason B; Hendrickson, Linzy M; Garwood, Grant M; Toungate, Kelsey M; Nania, Christina V; Morikawa, Hitoshi

    2017-01-01

    Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3-4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity.

  1. Processing of vestibular inputs by the medullary lateral tegmental field of conscious cats: implications for generation of motion sickness

    Science.gov (United States)

    McCall, Andrew A.; Moy, Jennifer D.; DeMayo, William M.; Puterbaugh, Sonya R.; Miller, Daniel J.; Catanzaro, Michael F.

    2013-01-01

    The dorsolateral reticular formation of the caudal medulla, the lateral tegmental field (LTF), participates in generating vomiting. LTF neurons exhibited complex responses to vestibular stimulation in decerebrate cats, indicating that they received converging inputs from a variety of labyrinthine receptors. Such a convergence pattern of vestibular inputs is appropriate for a brain region that participates in generating motion sickness. Since responses of brainstem neurons to vestibular stimulation can differ between decerebrate and conscious animals, the current study examined the effects of whole-body rotations in vertical planes on the activity of LTF neurons in conscious felines. Wobble stimuli, fixed-amplitude tilts, the direction of which moves around the animal at a constant speed, were used to determine the response vector orientation, and also to ascertain whether neurons had spatial–temporal convergence (STC) behavior (which is due to the convergence of vestibular inputs with different spatial and temporal properties). The proportion of LTF neurons with STC behavior in conscious animals (25 %) was similar to that in decerebrate cats. Far fewer neurons in other regions of the feline brainstem had STC behavior, confirming findings that many LTF neurons receive converging inputs from a variety of labyrinthine receptors. However, responses to vertical plane vestibular stimulation were considerably different in decerebrate and conscious felines for LTF neurons lacking STC behavior. In decerebrate cats, most LTF neurons had graviceptive responses to rotations, similar to those of otolith organ afferents. However, in conscious animals, the response properties were similar to those of semicircular canal afferents. These differences show that higher centers of the brain that are removed during decerebration regulate the labyrinthine inputs relayed to the LTF, either by gating connections in the brainstem or by conveying vestibular inputs directly to the region

  2. Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking

    Science.gov (United States)

    Hendrickson, Linzy M.; Garwood, Grant M.; Toungate, Kelsey M.; Nania, Christina V.; Morikawa, Hitoshi

    2017-01-01

    Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3–4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity. PMID:28859110

  3. Role of ventral tegmental area glial cell line-derived neurotrophic factor in incubation of cocaine craving.

    Science.gov (United States)

    Lu, Lin; Wang, Xi; Wu, Ping; Xu, Chunmei; Zhao, Mei; Morales, Marisela; Harvey, Brandon K; Hoffer, Barry J; Shaham, Yavin

    2009-07-15

    Ventral tegmental area (VTA) brain-derived neurotrophic factor (BDNF) contributes to time-dependent increases in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Here, we studied the role of glial cell line-derived neurotrophic factor (GDNF) in incubation of cocaine craving because, like BDNF, GDNF provides trophic support to midbrain dopamine neurons. We first trained rats to self-administer intravenous cocaine for 10 days (6 hours/d, cocaine injections were paired with a tone-light cue). We then manipulated VTA GDNF function and assessed cue-induced cocaine seeking in extinction tests after withdrawal from cocaine. VTA injections of an adeno-associated virus (AAV) vector containing rat GDNF cDNA (5 x 10(8) viral genomes) on withdrawal Day 1 increased cue-induced cocaine seeking on withdrawal days 11 and 31; this effect was not observed after VTA injections of an AAV viral vector containing red fluorescent protein (RFP). Additionally, VTA, but not substantial nigra (SN), GDNF injections (1.25 microg or 12.5 microg/side) immediately after the last cocaine self-administration session increased cue-induced drug seeking on withdrawal days 3 and 10; this effect was reversed by VTA injections of U0126, which inhibits the activity of extracellular signal-regulated kinases (ERK). Finally, interfering with VTA GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies via minipumps (600 ng/side/d) during withdrawal Days 1-14 prevented the time-dependent increases in cue-induced cocaine seeking on withdrawal days 11 and 31. Our results indicate that during the first weeks of withdrawal from cocaine self-administration, GDNF-dependent neuroadaptations in midbrain VTA neurons play an important role in the development of incubation of cocaine craving.

  4. Music and the nucleus accumbens.

    Science.gov (United States)

    Mavridis, Ioannis N

    2015-03-01

    Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA.

  5. INTERACCION MOLECULAR DE LOS RECEPTORES CRH-R2 Y DA-D1 EN EL AREA TEGMENTAL VENTRAL DE RATA

    OpenAIRE

    ARAYA GUTIERREZ, KATHERINE ANGELICA

    2013-01-01

    La administración repetida de drogas de abuso genera cambios plásticos perdurables que se traducen en alteraciones en las propiedades funcionales de las neuronas del sistema mesocorticolímbico, como lo es la sensibilización de la liberación de glutamato en el área tegmental ventral (VTA) inducida por la administración repetida de cocaína, esto determina la recaída a la droga (Wang y cols. 2005). Dicha sensibilización estaría siendo modulada por la activación de receptores dopam...

  6. Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats.

    Science.gov (United States)

    Ding, Zheng-Ming; Ingraham, Cynthia M; Rodd, Zachary A; McBride, William J

    2016-10-01

    Repeated local administration of ethanol (EtOH) sensitized the posterior ventral tegmental area (pVTA) to the local dopamine (DA)-stimulating effects of EtOH. Chronic alcohol drinking increased nucleus accumbens (NAC) DA transmission and pVTA glutamate transmission in alcohol-preferring (P) rats. The objectives of the present study were to determine the effects of chronic alcohol drinking by P rats on the (a) sensitivity and response of the pVTA DA neurons to the DA-stimulating actions of EtOH, and (b) negative feedback control of DA (via D2 auto-receptors) and glutamate (via group II mGlu auto-receptors) release in the pVTA. EtOH (50 or 150 mg%) or the D2/3 receptor antagonist sulpiride (100 or 200 μM) was microinjected into the pVTA while DA was sampled with microdialysis in the NAC shell (NACsh). The mGluR2/3 antagonist LY341495 (1 or 10 μM) was perfused through the pVTA via reverse microdialysis and local extracellular glutamate and DA levels were measured. EtOH produced a more robust increase of NACsh DA in the 'EtOH' than 'Water' groups (e.g., 150 mg% EtOH: to ∼ 210 vs 150% of baseline). In contrast, sulpiride increased DA release in the NACsh more in the 'Water' than 'EtOH' groups (e.g., 200 μM sulpiride: to ∼ 190-240 vs 150-160% of baseline). LY341495 (at 10 μM) increased extracellular glutamate and DA levels in the 'Water' (to ∼ 150-180% and 180-230% of baseline, respectively) but not the 'EtOH' groups. These results indicate that alcohol drinking enhanced the DA-stimulating effects of EtOH, and attenuated the functional activities of D2 auto-receptors and group II mGluRs within the pVTA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Study of Hadron Production in Hadron-Nucleus and Nucleus-Nucleus Collisions at the CERN SPS

    CERN Multimedia

    Selyuzhenkov, I; Klochkov, V; Herve, A E; Kowalski, S; Kaptur, E A; Kowalik, K L; Dominik, W M; Matulewicz, T N; Krasnoperov, A; Feofilov, G; Vinogradov, L; Kovalenko, V; Johnson, S R; Mills, G B; Planeta, R J; Rubbia, A; Marton, K; Messerly, B A; Puzovic, J; Bogomilov, M V; Bravar, A; Renfordt, R A E; Deveaux, M; Engel, R R; Grzeszczuk, A; Davis, N; Kuich, M; Lyubushkin, V; Kondratev, V; Kadija, K; Diakonos, F; Slodkowski, M A; Rauch, W H; Pistillo, C; Laszlo, A; Nakadaira, T; Hasegawa, T; Sadovskiy, A; Morozov, S; Petukhov, O; Mathes, H; Roehrich, D; Marcinek, A J; Marino, A D; Grebieszkow, K; Wlodarczyk, Z; Rybczynski, M A; Wojtaszek-szwarc, A; Nirkko, M C; Sakashita, K; Golubeva, M; Kurepin, A; Manic, D; Kolev, D I; Kisiel, J E; Koziel, M E; Rondio, E; Larsen, D T; Czopowicz, T R; Seyboth, P; Turko, L; Guber, F; Marin, V; Busygina, O; Strikhanov, M; Taranenko, A; Cirkovic, M; Roth, M A; Pulawski, S M; Aduszkiewicz, A M; Bunyatov, S; Vechernin, V; Nagai, Y; Anticic, T; Dynowski, K M; Mackowiak-pawlowska, M K; Stefanek, G; Pavin, M; Fodor, Z P; Nishikawa, K; Tada, M; Blondel, A P P; Stroebele, H W; Posiadala, M Z; Kolesnikov, V; Andronov, E; Zimmerman, E D; Antoniou, N; Majka, Z; Di luise, S; Veberic, D; Dumarchez, J; Naskret, M; Ivashkin, A; Tsenov, R V; Koziel, M G; Schmidt, K J; Melkumov, G; Popov, B; Panagiotou, A; Richter-was, E M; Ereditato, A; Paolone, V; Damyanova, A; Gazdzicki, M; Unger, M T; Wilczek, A G; Stepaniak, J M; Seryakov, A; Susa, T; Staszel, P P; Brzychczyk, J; Maksiak, B; Tefelski, D B

    2007-01-01

    The NA61/SHINE (SHINE = SPS Heavy Ion and Neutrino Experiment) experiment is a large acceptance hadron spectrometer at the CERN SPS for the study of the hadronic final states produced in interactions of various beam particles (pions, protons, C, S and In) with a variety of fixed targets at the SPS energies. The main components of the current detector were constructed and used by the NA49 experiment. The physics program of NA61/SHINE consists of three main subjects. In the first stage of data taking (2007-2009) measurements of hadron production in hadron-nucleus interactions needed for neutrino (T2K) and cosmic-ray (Pierre Auger and KASCADE) experiments will be performed. In the second stage (2009-2011) hadron production in proton-proton and proton-nucleus interactions needed as reference data for a better understanding of nucleus-nucleus reactions will be studied. In the third stage (2009-2013) energy dependence of hadron production properties will be measured in nucleus-nucleus collisions as well as in p+p a...

  8. Nucleus accumbens surgery for addiction.

    Science.gov (United States)

    Li, Nan; Wang, Jing; Wang, Xue-lian; Chang, Chong-wang; Ge, Shun-nan; Gao, Li; Wu, He-ming; Zhao, Hai-kang; Geng, Ning; Gao, Guo-dong

    2013-01-01

    Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery because of psychological dependence. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. Based on animal experiments, our institute started the clinical trial for the treatment of drug addicts' psychological dependence by making lesions in the bilateral NAc with stereotactic surgery from July 2000. The short-term outcomes were encouraging and triggered rapid application of this treatment in China from 2003 to 2004. However, lack of long-term outcomes and controversy eventually led to halting the surgery for addiction by the Ministry of Health of China in November 2004 and a nationwide survey about it later. Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow-up study showed that the 5-year nonrelapse rate was 58% and the quality of life was significantly improved. Patients had several kinds of side effects, but the incidence rate was relatively low. The patients gradually recovered more than 5 years after the surgery. The side effects did not severely influence an individual's life or work. Nationwide surgery showed that the nonrelapse rate was 50% in the sample of 150 cases, from 1167 patients overall who underwent stereotactic surgery in China. Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location has a significant impact on treatment efficacy and requires further study. Because ablation is irreversible, the NAc surgery for addiction should be performed with cautiousness, and deep brain stimulation (DBS) is an ideal alternative. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Large philipsite crystal as ferromanganese nodule nucleus

    Digital Repository Service at National Institute of Oceanography (India)

    Ghosh, A.K.; Mukhopadhyay, R.

    We report here the occurrence of, to date, the largest (21 x 10 x 8 mm) phillipsite crystal forming the nucleus of a diagenetically formed ferromanganese nodule from the Central Indian Ocean Basin (CIOB). Assuming an average rate of ferromanganese...

  10. Testing string dynamics in lepton nucleus reactions

    Energy Technology Data Exchange (ETDEWEB)

    Gyulassy, M.; Pluemer, M.

    1989-10-01

    The sensitivity of nuclear attenuation of 10-100 GeV lepton nucleus ({ell}A) reactions to space-time aspects of hadronization is investigated within the context of the Lund string model. We consider two mechanisms for attenuation in a nucleus: final state cascading and string flip excitations. Implications for the evolution of the energy density in nuclear collisions are discussed. 16 refs., 10 figs.

  11. Advances in hard nucleus cataract surgery

    Directory of Open Access Journals (Sweden)

    Wei Cui

    2013-11-01

    Full Text Available Security and perfect vision and fewer complications are our goals in cataract surgery, and hard-nucleus cataract surgery is always a difficulty one. Many new studies indicate that micro-incision phacoemulsification in treating hard nucleus cataract is obviously effective. This article reviews the evolution process of hard nuclear cataract surgery, the new progress in the research of artificial intraocular lens for microincision, and analyse advantages and disadvantages of various surgical methods.

  12. Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation.

    Science.gov (United States)

    Zhang, Jian-Ping; Xu, Qi; Yuan, Xiang-Shan; Cherasse, Yoan; Schiffmann, Serge N; de Kerchove d'Exaerde, Alban; Qu, Wei-Min; Urade, Yoshihiro; Lazarus, Michael; Huang, Zhi-Li; Li, Rui-Xi

    2013-01-01

    Adenosine A2A receptors (A2ARs) in the nucleus accumbens (Acb) have been demonstrated to play an important role in the arousal effect of adenosine receptor antagonist caffeine, and may be involved in physiological sleep. To better understand the functions of these receptors in sleep, projections of A2AR neurons were mapped utilizing adeno-associated virus (AAV) encoding humanized Renilla green fluorescent protein (hrGFP) as a tracer for long axonal pathways. The Cre-dependent AAV was injected into the core (AcbC) and shell (AcbSh) of the Acb in A2AR-Cre mice. Immunohistochemistry was then used to visualize hrGFP, highlighting the perikarya of the A2AR neurons in the injection sites, and their axons in projection regions. The data revealed that A2AR neurons exhibit medium-sized and either round or elliptic perikarya with their processes within the Acb. Moreover, the projections from the Acb distributed to nuclei in the forebrain, diencephalon, and brainstem. In the forebrain, A2AR neurons from all Acb sub-regions jointly projected to the ventral pallidum, the nucleus of the diagonal band, and the substantia innominata. Heavy projections from the AcbC and the ventral AcbSh, and weaker projections from the medial AcbSh, were observed in the lateral hypothalamus and lateral preoptic area. In the brainstem, the Acb projections were found in the ventral tegmental area, while AcbC and ventral AcbSh also projected to the median raphe nucleus, the dorsal raphe nucleus, and the ventrolateral periaqueductal gray. The results supply a solid base for understanding the roles of the A2AR and A2AR neurons in the Acb, especially in the regulation of sleep.

  13. Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation

    Directory of Open Access Journals (Sweden)

    Jianping eZhang

    2013-12-01

    Full Text Available Adenosine A2A receptors (A2ARs in the nucleus accumbens (Acb have been demonstrated to play an important role in the arousal effect of adenosine receptor antagonist caffeine, and may be involved in physiological sleep. To better understand the functions of these receptors in sleep, projections of A2AR neurons were mapped utilizing adeno-associated virus (AAV encoding humanized Renilla green fluorescent protein (hrGFP as a tracer for long axonal pathways. The Cre-dependent AAV was injected into the core (AcbC and shell (AcbSh of the Acb in A2AR-Cre mice. Immunohistochemistry was then used to visualize hrGFP, highlighting the perikarya of the A2AR neurons in the injection sites, and their axons in projection regions. The data revealed that A2AR neurons exhibit medium-sized and either round or elliptic perikarya with their processes within the Acb. Moreover, the projections from the Acb distributed to nuclei in the forebrain, diencephalon, and brainstem. In the forebrain, A2AR neurons from all Acb sub-regions jointly projected to the ventral pallidum, the nucleus of the diagonal band, and the substantia innominata. Heavy projections from the AcbC and the ventral AcbSh, and weaker projections from the medial AcbSh, were observed in the lateral hypothalamus and lateral preoptic area. In the brainstem, the Acb projections were found in the ventral tegmental area, while AcbC and ventral AcbSh also projected to the median raphe nucleus, the dorsal raphe nucleus, and the ventrolateral periaqueductal gray. The results supply a solid base for understanding the roles of the A2AR and A2AR neurons in the Acb, especially in the regulation of sleep.

  14. Prenatal Ethanol Exposure Persistently Alters Endocannabinoid Signaling and Endocannabinoid-Mediated Excitatory Synaptic Plasticity in Ventral Tegmental Area Dopamine Neurons.

    Science.gov (United States)

    Hausknecht, Kathryn; Shen, Ying-Ling; Wang, Rui-Xiang; Haj-Dahmane, Samir; Shen, Roh-Yu

    2017-06-14

    Prenatal ethanol exposure (PE) leads to increased addiction risk which could be mediated by enhanced excitatory synaptic strength in ventral tegmental area (VTA) dopamine (DA) neurons. Previous studies have shown that PE enhances excitatory synaptic strength by facilitating an anti-Hebbian form of long-term potentiation (LTP). In this study, we investigated the effect of PE on endocannabinoid-mediated long-term depression (eCB-LTD) in VTA DA neurons. Rats were exposed to moderate (3 g/kg/d) or high (6 g/kg/d) levels of ethanol during gestation. Whole-cell recordings were conducted in male offspring between 4 and 10 weeks old.We found that PE led to increased amphetamine self-administration. Both moderate and high levels of PE persistently reduced low-frequency stimulation-induced eCB-LTD. Furthermore, action potential-independent glutamate release was regulated by tonic eCB signaling in PE animals. Mechanistic studies for impaired eCB-LTD revealed that PE downregulated CB1 receptor function. Interestingly, eCB-LTD in PE animals was rescued by metabotropic glutamate receptor I activation, suggesting that PE did not impair the synthesis/release of eCBs. In contrast, eCB-LTD in PE animals was not rescued by increasing presynaptic activity, which actually led to LTP in PE animals, whereas LTD was still observed in controls. This result shows that the regulation of excitatory synaptic plasticity is fundamentally altered in PE animals. Together, PE leads to impaired eCB-LTD at the excitatory synapses of VTA DA neurons primarily due to CB1 receptor downregulation. This effect could contribute to enhanced LTP and the maintenance of augmented excitatory synaptic strength in VTA DA neurons and increased addiction risk after PE. SIGNIFICANCE STATEMENT Prenatal ethanol exposure (PE) is among many adverse developmental factors known to increase drug addiction risk. Increased excitatory synaptic strength in VTA DA neurons is a critical cellular mechanism for addiction risk. Our

  15. Improved Cloud Condensation Nucleus Spectrometer

    Science.gov (United States)

    Leu, Ming-Taun

    2010-01-01

    An improved thermal-gradient cloud condensation nucleus spectrometer (CCNS) has been designed to provide several enhancements over prior thermal- gradient counters, including fast response and high-sensitivity detection covering a wide range of supersaturations. CCNSs are used in laboratory research on the relationships among aerosols, supersaturation of air, and the formation of clouds. The operational characteristics of prior counters are such that it takes long times to determine aerosol critical supersaturations. Hence, there is a need for a CCNS capable of rapid scanning through a wide range of supersaturations. The present improved CCNS satisfies this need. The improved thermal-gradient CCNS (see Figure 1) incorporates the following notable features: a) The main chamber is bounded on the top and bottom by parallel thick copper plates, which are joined by a thermally conductive vertical wall on one side and a thermally nonconductive wall on the opposite side. b) To establish a temperature gradient needed to establish a supersaturation gradient, water at two different regulated temperatures is pumped through tubes along the edges of the copper plates at the thermally-nonconductive-wall side. Figure 2 presents an example of temperature and supersaturation gradients for one combination of regulated temperatures at the thermally-nonconductive-wall edges of the copper plates. c) To enable measurement of the temperature gradient, ten thermocouples are cemented to the external surfaces of the copper plates (five on the top plate and five on the bottom plate), spaced at equal intervals along the width axis of the main chamber near the outlet end. d) Pieces of filter paper or cotton felt are cemented onto the interior surfaces of the copper plates and, prior to each experimental run, are saturated with water to establish a supersaturation field inside the main chamber. e) A flow of monodisperse aerosol and a dilution flow of humid air are introduced into the main

  16. High-frequency stimulation of nucleus accumbens changes in dopaminergic reward circuit.

    Directory of Open Access Journals (Sweden)

    Na Yan

    Full Text Available Deep brain stimulation (DBS of the nucleus accumbens (NAc is a potential remedial therapy for drug craving and relapse, but the mechanism is poorly understood. We investigated changes in neurotransmitter levels during high frequency stimulation (HFS of the unilateral NAc on morphine-induced rats. Sixty adult Wistar rats were randomized into five groups: the control group (administration of saline, the morphine-only group (systematic administration of morphine without electrode implantation, the morphine-sham-stimulation group (systematic administration of morphine with electrode implantation but not given stimulation, the morphine-stimulation group (systematic administration of morphine with electrode implantation and stimulation and the saline-stimulation group (administration of saline with electrode implantation and stimulation. The stimulation electrode was stereotaxically implanted into the core of unilateral NAc and microdialysis probes were unilaterally lowered into the ipsilateral ventral tegmental area (VTA, NAc, and ventral pallidum (VP. Samples from microdialysis probes in the ipsilateral VTA, NAc, and VP were analyzed for glutamate (Glu and γ-aminobutyric acid (GABA by high-performance liquid chromatography (HPLC. The levels of Glu were increased in the ipsilateral NAc and VP of morphine-only group versus control group, whereas Glu levels were not significantly changed in the ipsilateral VTA. Furthermore, the levels of GABA decreased significantly in the ipsilateral NAc, VP, and VTA of morphine-only group when compared with control group. The profiles of increased Glu and reduced GABA in morphine-induced rats suggest that the presence of increased excitatory neurotransmission in these brain regions. The concentrations of the Glu significantly decreased while the levels of GABA increased in ipsilateral VTA, NAc, and VP in the morphine-stimulation group compared with the morphine-only group. No significant changes were seen in the

  17. The retrograde connections and anatomical segregation of the Göttingen minipig nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Anders Christian Meidahl

    2016-12-01

    Full Text Available Nucleus accumbens (NAcc has been implicated in several psychiatric disorders such as treatment resistant depression (TRD and obsessive-compulsive disorder (OCD, and has been an ongoing experimental target for deep brain stimulation (DBS in both rats and humans. In order to translate basic scientific results from rodents to the human setting a large animal model is needed to thoroughly study the effect of such therapeutic interventions. The aim of the study was, accordingly, to describe the basic anatomy of the Göttingen minipig NAcc and its retrograde connections.Tracing was carried out by MRI-guided stereotactic unilateral fluorogold injections in the NAcc of Göttingen minipigs. After two weeks the brains were sectioned and subsequently stained with Nissl-, autometallographic (AMG development of myelin, and DARPP-32 and calbindin immunohistochemistry.The minipig NAcc was divided in a central core and an outer medial, ventral and lateral shell. We confirmed the NAcc to be a large and well-segregated structure towards its medial, ventral and lateral borders. The fluorogold tracing revealed inputs to NAcc from the medial parts of the prefrontal cortex, BA 25 (subgenual cortex, insula bilaterally, amygdala, the CA1-region of hippocampus, entorhinal cortex, subiculum, paraventricular and anterior parts of thalamus, dorsomedial parts of hypothalamus, substantia nigra, ventral tegmental area, the retrorubral field and the dorsal and median raphe nuclei.In conclusion the Göttingen minipig NAcc is a large ventral striatal structure that can be divided into a core and shell with prominent afferent connections from several subrhinal and infra-/prelimbic brain areas.

  18. The role of D-serine as co-agonist of NMDA receptors in the nucleus accumbens: relevance to cocaine addiction

    Directory of Open Access Journals (Sweden)

    Marcello eD'Ascenzo

    2014-07-01

    Full Text Available Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rate of relapse during periods of abstinence. Increasing consensus suggests that addiction to drugs of abuse usurps learning and memory mechanisms normally related to natural rewards, ultimately producing long-lasting neuroadaptations in the mesocorticolimbic system. This system, formed in part by the ventral tegmental area and nucleus accumbens (NAc, has a central role in the development and expression of addictive behaviors. In addition to a broad spectrum of changes that affect morphology and function of NAc excitatory circuits in cocaine–treated animals, impaired N-methyl-D-aspartate receptor (NMDAR-dependent synaptic plasticity is a typical feature. D-serine, a D-amino acid that has been found at high levels in mammalian brain, binds with high affinity the co-agonist site of NMDAR and mediates, along with glutamate, several important processes including synaptic plasticity. Here we review recent literature focusing on cocaine-induced impairment in synaptic plasticity mechanisms in the NAc and on the fundamental role of D-serine as co-agonist of NMDAR in functional and dysfunctional synaptic plasticity within this nucleus. The emerging picture is that reduced D-serine levels play a crucial role in synaptic plasticity relevant to cocaine addiction. This finding opens new perspectives for therapeutic approaches to treat this addictive state.

  19. A-Dependence of $\\pi^0$-Meson Production in Proton-Nucleus and Nucleus-Nucleus Collisions at High Energies

    CERN Document Server

    Tokarev, M V; Dedovich, T G

    2000-01-01

    The A-dependence of pi^0-meson production in proton-nucleus and nucleus-nucleus collisions at a high transverse momentum is studied. The concept of z-scaling reflecting the general features of particle interactions is developed for the description of pi^0-meson production. Experimental data on the cross section obtained at ISR, SpS and Tevatron are usen in the analysis. The A-dependence of scale transformation z to alpha cdot z, psi to alpha^-1 cdot psi is established. An indication of the power law, psi (z) approx z^-beta, at high p_T > 4 GeV/c is found. Based on the properties of z-scaling, the dependence of the cross section of pi^0-mesons produced in pA and AA collisions on transverse momentum over the central rapidity range at RHIC energies is predicted.

  20. Open heavy-flavour production in high energy nucleus-nucleus collisions

    NARCIS (Netherlands)

    Mischke, A.

    2010-01-01

    Heavy quarks (charm and bottom) provide sensitive penetrating probes of hot quark matter produced in high energy nucleus-nucleus collisions. Due to their large mass, heavy quarks are believed to be predominantly produced in the initial state of the collision by gluon fusion processes. The study

  1. Observation of high energy gamma rays in intermediate energy nucleus-nucleus collisions

    NARCIS (Netherlands)

    Beard, K.B.; Benenson, W.; Bloch, C.; Kashy, E.; Stevenson, J.; Morrissey, D.J.; Plicht, J. van der; Sherrill, B.; Winfield, J.S.

    1985-01-01

    High energy electrons and positrons observed in medium energy nucleus-nucleus collisions are shown to be primarily due to the external conversion of high energy gamma rays. The reaction 14N+Cu was studied at E/A=40 MeV, and a magnetic spectrograph was used with a specially constructed multiwire

  2. Structural dynamics of the cell nucleus

    Science.gov (United States)

    Wiegert, Simon; Bading, Hilmar

    2011-01-01

    Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons. PMID:21738832

  3. Cell Biology of the Caenorhabditis elegans Nucleus.

    Science.gov (United States)

    Cohen-Fix, Orna; Askjaer, Peter

    2017-01-01

    Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology. Copyright © 2017 by the Genetics Society of America.

  4. UNCOVERING THE NUCLEUS CANDIDATE FOR NGC 253

    Energy Technology Data Exchange (ETDEWEB)

    Günthardt, G. I.; Camperi, J. A. [Observatorio Astronómico, Universidad Nacional de Córdoba (Argentina); Agüero, M. P. [Observatorio Astronómico, Universidad Nacional de Córdoba, and CONICET (Argentina); Díaz, R. J.; Gomez, P. L.; Schirmer, M. [Gemini Observatory, AURA (United States); Bosch, G., E-mail: gunth@oac.uncor.edu, E-mail: camperi@oac.uncor.edu, E-mail: mpaguero@oac.uncor.edu, E-mail: rdiaz@gemini.edu, E-mail: pgomez@gemini.edu, E-mail: mschirmer@gemini.edu, E-mail: guille@fcaglp.unlp.edu.ar [Instituto de Astrofísica de La Plata (CONICET-UNLP) (Argentina)

    2015-11-15

    NGC 253 is the nearest spiral galaxy with a nuclear starburst that becomes the best candidate for studying the relationship between starburst and active galactic nucleus activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus to the point that there is no strong evidence that the galaxy harbors a supermassive black hole co-evolving with the starburst as was supposed earlier. Near-infrared (NIR) spectroscopy, especially NIR emission line analysis, could be advantageous in shedding light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis of the central structure and through the brightest infrared source. In this work, we present evidence showing that the brightest NIR and mid-infrared source in the central region, already known as radio source TH7 and so far considered just a large stellar supercluster, in fact presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. Mentioning some distinctive aspects, it is the most massive compact infrared object in the central region, located at 2.″0 of the symmetry center of the galactic bar, as measured in the K-band emission. Moreover, our data indicate that this object is surrounded by a large circumnuclear stellar disk and it is also located at the rotation center of the large molecular gas disk of NGC 253. Furthermore, a kinematic residual appears in the H{sub 2} rotation curve with a sinusoidal shape consistent with an outflow centered in the candidate nucleus position. The maximum outflow velocity is located about 14 pc from TH7, which is consistent with the radius of a shell detected around the nucleus candidate, observed at 18.3 μm (Qa) and 12.8 μm ([Ne ii]) with T-ReCS. Also, the Brγ emission line profile shows a pronounced blueshift and this emission line also has the highest equivalent width at this

  5. Decoding calcium signaling across the nucleus.

    Science.gov (United States)

    Oliveira, André G; Guimarães, Erika S; Andrade, Lídia M; Menezes, Gustavo B; Fatima Leite, M

    2014-09-01

    Calcium (Ca(2+)) is an important multifaceted second messenger that regulates a wide range of cellular events. A Ca(2+)-signaling toolkit has been shown to exist in the nucleus and to be capable of generating and modulating nucleoplasmic Ca(2+) transients. Within the nucleus, Ca(2+) controls cellular events that are different from those modulated by cytosolic Ca(2+). This review focuses on nuclear Ca(2+) signals and their role in regulating physiological and pathological processes. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

  6. Direct projection from the suprachiasmatic nucleus to hypophysiotrophic corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus of the hypothalamus demonstrated...

    DEFF Research Database (Denmark)

    Vrang, N.; Larsen, P.J.; Mikkelsen, J.D.

    1995-01-01

    Suprachiasmatic nucleus, paraventricular nucleus, circadian rhythms, phaseolus vulgaris-leucoagglutinin, corticotropin-releasing factor, dual immunocytochemistry......Suprachiasmatic nucleus, paraventricular nucleus, circadian rhythms, phaseolus vulgaris-leucoagglutinin, corticotropin-releasing factor, dual immunocytochemistry...

  7. TWO-PHOTON PHYSICS IN NUCLEUS-NUCLEUS COLLISIONS AT RHIC.

    Energy Technology Data Exchange (ETDEWEB)

    NYSTRAND,J.

    1998-09-10

    Ultra-relativistic heavy-ions carry strong electromagnetic and nuclear fields. Interactions between these fields in peripheral nucleus-nucleus collisions can probe many interesting physics topics. This presentation will focus on coherent two-photon and photonuclear processes at RHIC. The rates for these interactions will be high. The coherent coupling of all the protons in the nucleus enhances the equivalent photon flux by a factor Z{sup 2} up to an energy of {approx} 3 GeV. The plans for studying coherent interactions with the STAR experiment will be discussed. Experimental techniques for separating signal from background will be presented.

  8. Two-photon physics in nucleus-nucleus collisions at RHIC

    Energy Technology Data Exchange (ETDEWEB)

    Nystrand, J.; Klein, S.

    1998-09-01

    Ultra-relativistic heavy-ions carry strong electromagnetic and nuclear fields. Interactions between these fields in peripheral nucleus-nucleus collisions can probe many interesting physics topics. This presentation will focus on coherent two-photon and photonuclear processes at RHIC. The rates for these interactions will be high. The coherent coupling of all the protons in the nucleus enhances the equivalent photon flux by a factor Z{sup 2} up to an energy of {approx} 3 GeV. The plans for studying coherent interactions with the STAR experiment will be discussed. Experimental techniques for separating signal from background will be presented.

  9. ULTRASTRUCTURE OF THE RAT MESENCEPHALIC TRIGEMINAL NUCLEUS

    NARCIS (Netherlands)

    LIEM, RSB; COPRAY, JCVM; VANWILLIGEN, JD

    The subcellular morphology of the mesencephalic trigeminal (Me5) nucleus in the rat was studied by transmission electron microscopy. Most neurons in the thin rostral as well as in the major caudal part of Me5 appeared as large (40-50-mu-m), round-to ovoid-shaped unipolar cells. A few neurons

  10. Resonances in η-light nucleus systems

    Indian Academy of Sciences (India)

    2Departamento de Fisica, Universidad de los Andes, Bogota, Colombia. E-mail: kanchanp@magnum.barc.ernet.in. Abstract. We locate resonances in η-light nucleus elastic scattering using the time delay method. We solve few-body equations within the finite rank approximation in order to calculate the t-matrices and hence ...

  11. Oral alprazolam acutely increases nucleus accumbens perfusion

    OpenAIRE

    Wolf, Daniel H.; Pinkham, Amy E.; Satterthwaite, Theodore D.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey; Smith, Mark A.; Detre, John A.; Gur, Ruben C.; Gur, Raquel E.

    2012-01-01

    Benzodiazepines treat anxiety, but can also produce euphoric effects, contributing to abuse. Using perfusion magnetic resonance imaging, we provide the first direct evidence in humans that alprazolam (Xanax) acutely increases perfusion in the nucleus accumbens, a key reward-processing region linked to addiction.

  12. Resonances in η-light nucleus systems

    Indian Academy of Sciences (India)

    We locate resonances in -light nucleus elastic scattering using the time delay method. We solve few-body equations within the finite rank approximation in order to calculate the -matrices and hence the time delay for the - 3He and - 4He systems. We find a resonance very close to the threshold in - 3 He elastic ...

  13. The Checkerboard Model of the Nucleus

    Science.gov (United States)

    Lach, Theodore

    2015-04-01

    The Checker Board Model (CBM) of the nucleus and the associated extended standard model predicts that nature has 5 generations of quarks not 3 and that Nucleus is 2 dimensional. The CBM theory began with an insight into the structure of the He nucleus around the year 1989. Details of how this theory evolved which took many years, and is found on my web site (http://checkerboard.dnsalias.net) or in the following references One independent check of this model is that the wavelength of the ``up'' quark orbiting inside the proton at 84.8123% the speed of light (around the ``dn'' quark in the center of the proton) turns out to be exactly one de Broglie wavelength something determined after the mass and speed of the up quark were determined by other means. This theory explains the mass of the proton and neutron and their magnetic moments and this along with the beautiful symmetric 2D structure of the He nucleus led to the evolution of this theory. When this theory was first presented at Argonne in 1996, it was the first time that anyone had predicted the quarks orbited inside the proton at relativistic speeds and it was met with skepticism.

  14. Compound nucleus studies withy reverse kinematics

    Energy Technology Data Exchange (ETDEWEB)

    Moretto, L.G.

    1985-06-01

    Reverse kinematics reactions are used to demonstrate the compound nucleus origin of intermediate mass particles at low energies and the extension of the same mechanism at higher energies. No evidence has appeared in our energy range for liquid-vapor equilibrium or cold fragmentation mechanisms. 11 refs., 12 figs.

  15. Suprachiasmatic Nucleus Interaction with the Arcuate Nucleus; Essential for Organizing Physiological Rhythms

    NARCIS (Netherlands)

    Buijs, Frederik N.; Guzmán-Ruiz, Mara; León-Mercado, Luis; Basualdo, Mari Carmen; Escobar, Carolina; Kalsbeek, Andries; Buijs, Ruud M.

    2017-01-01

    The suprachiasmatic nucleus (SCN) is generally considered the master clock, independently driving all circadian rhythms. We recently demonstrated the SCN receives metabolic and cardiovascular feedback adeptly altering its neuronal activity. In the present study, we show that microcuts effectively

  16. Nonequilibrium distribution functions of nucleons in relativistic nucleus-nucleus collisions

    Directory of Open Access Journals (Sweden)

    D. Anchishkin

    2013-03-01

    Full Text Available The collision smearing of the nucleon momenta about their initial values during relativistic nucleus-nucleus collisions is investigated. To a certain degree, our model belongs to the transport type, and we investigate the evolution of the nucleon system created at a nucleus-nucleus collision. However, we parameterize this development by the number of collisions of every particle during evolution rather than by the time variable. It is assumed that the group of nucleons which leave the system after the same number of collisions can be joined in a particular statistical ensemble. The nucleon nonequilibrium distribution functions are derived which depend on a certain number of collisions of a nucleon before a freeze-out.

  17. The production of strangeness and charmonium in nucleus-nucleus collisions

    CERN Document Server

    Geiss, J

    1998-01-01

    The aim of the present theis is to study the space-time evolution of highly relativistic nucleus-nucleus collisions in a microscopic purely hadronic transport theory. Especially the production of strangeness in nucleus-nucleus collisions over a large energy range from SIS- (E sub l sub a sub b =1-2 A.GeV) up to SPS-energies (E sub l sub a sub b +200 A.GeV) for many different systems are studied, whereby for the elementary production cross sections as conservative assumptions as possible are made. The aim is to obtain an excitation function for the production of strangeness over the whole energy range. Furthermore the production of J/psi particles at SPS energies is studied for different systems, whereby a new absorption mechanism of the c anti c pairs is tested.

  18. Strangeness production in antiproton-nucleus annihilation

    Directory of Open Access Journals (Sweden)

    Mosel U.

    2012-12-01

    Full Text Available The results of the microscopic transport calculations of p¯ $ar p$-nucleus interactions within a GiBUU model are presented. The dominating mechanism of hyperon production is the strangeness exchange processes K¯N $ar KN$ → γπ and K¯N $ar KN$ → ΞK. The calculated rapidity spectra of Ξ hyperons are significantly shifted to forward rapidities with respect to the spectra of S = −1 hyperons. We argue that this shift should be a sensitive test for the possible exotic mechanisms of p¯ $ar p$-nucleus annihilation. The production of the double Λ-hypernuclei by Ξ− interaction with a secondary target is calculated.

  19. Protein quality control in the nucleus

    DEFF Research Database (Denmark)

    Nielsen, Sofie V.; Poulsen, Esben Guldahl; Rebula, Caio A.

    2014-01-01

    to aggregate, cells have evolved several elaborate quality control systems to deal with these potentially toxic proteins. First, various molecular chaperones will seize the misfolded protein and either attempt to refold the protein or target it for degradation via the ubiquitin-proteasome system...... to be particularly active in protein quality control. Thus, specific ubiquitin-protein ligases located in the nucleus, target not only misfolded nuclear proteins, but also various misfolded cytosolic proteins which are transported to the nucleus prior to their degradation. In comparison, much less is known about...... these mechanisms in mammalian cells. Here we highlight recent advances in our understanding of nuclear protein quality control, in particular regarding substrate recognition and proteasomal degradation....

  20. Cell Biology of the Plant Nucleus.

    Science.gov (United States)

    Meier, Iris; Richards, Eric J; Evans, David E

    2017-04-28

    The eukaryotic nucleus is enclosed by the nuclear envelope, which is perforated by the nuclear pores, the gateways of macromolecular exchange between the nucleoplasm and cytoplasm. The nucleoplasm is organized in a complex three-dimensional fashion that changes over time and in response to stimuli. Within the cell, the nucleus must be viewed as an organelle (albeit a gigantic one) that is a recipient of cytoplasmic forces and capable of morphological and positional dynamics. The most dramatic reorganization of this organelle occurs during mitosis and meiosis. Although many of these aspects are less well understood for the nuclei of plants than for those of animals or fungi, several recent discoveries have begun to place our understanding of plant nuclei firmly into this broader cell-biological context.

  1. Development of a Mobile Ice Nucleus Counter

    Energy Technology Data Exchange (ETDEWEB)

    Kok, Gregory [Droplet Measurement Technologies, Boulder, CO (United States); Kulkarni, Gourihar [Droplet Measurement Technologies, Boulder, CO (United States)

    2014-07-10

    An ice nucleus counter has been constructed. The instrument uses built-in refrigeration systems for wall cooling. A cascade refrigeration system will allow the cold wall to operate as low as -70°C, and a single stage system can operate the warm wall at -45C. A unique optical particle counter has been constructed using polarization detection of the scattered light. This allows differentiation of the particles exiting the chamber to determine if they are ice or liquid.

  2. Systematics of $\\alpha$--nucleus optical potentials

    OpenAIRE

    Mohr, P; Abele, H.; Atzrott, U.; Staudt, G.; Bieber, R; Grün, K.; Oberhummer, H.; Rauscher, T.; Somorjai, E.

    1994-01-01

    Double--folded optical $\\alpha$--nucleus potentials can be used to calculate elastic scattering cross sections in a wide mass-- and energy region. Because of the systematic behavior of the potential parameters we are able to obtain reliable optical potentials for astrophysically relevant reactions even without scattering data in low--energy region. As example we analyze the capture reaction ${^{144}{\\rm Sm}}(\\alpha,\\gamma){^{148}{\\Gd}}$.

  3. Improved Neuroimaging Atlas of the Dentate Nucleus.

    Science.gov (United States)

    He, Naying; Langley, Jason; Huddleston, Daniel E; Ling, Huawei; Xu, Hongmin; Liu, Chunlei; Yan, Fuhua; Hu, Xiaoping P

    2017-07-01

    The dentate nucleus (DN) of the cerebellum is the major output nucleus of the cerebellum and is rich in iron. Quantitative susceptibility mapping (QSM) provides better iron-sensitive MRI contrast to delineate the boundary of the DN than either T2-weighted images or susceptibility-weighted images. Prior DN atlases used T2-weighted or susceptibility-weighted images to create DN atlases. Here, we employ QSM images to develop an improved dentate nucleus atlas for use in imaging studies. The DN was segmented in QSM images from 38 healthy volunteers. The resulting DN masks were transformed to a common space and averaged to generate the DN atlas. The center of mass of the left and right sides of the QSM-based DN atlas in the Montreal Neurological Institute space was -13.8, -55.8, and -36.4 mm, and 13.8, -55.7, and -36.4 mm, respectively. The maximal probability and mean probability of the DN atlas with the individually segmented DNs in this cohort were 100 and 39.3%, respectively, in contrast to the maximum probability of approximately 75% and the mean probability of 23.4 to 33.7% with earlier DN atlases. Using QSM, which provides superior iron-sensitive MRI contrast for delineating iron-rich structures, an improved atlas for the dentate nucleus has been generated. The atlas can be applied to investigate the role of the DN in both normal cortico-cerebellar physiology and the variety of disease states in which it is implicated.

  4. Low P sub T hadron-nucleus interactions

    Science.gov (United States)

    Holynski, R.; Wozniak, K.

    1985-01-01

    The possibility of describing hadron-nucleus (hA) interactions is discussed in terms of a number of independent collisions of the projectile inside the target nucleus. This multiple rescattering may occur on a particle or quark parton level. To investigate the characteristics of hA interactions as a function of antineutrinos advantage is taken of the correlation between the average number antineutrinos of collisions of the projectile inside the nucleus and the number Ng of fast protons ejected from the struck nucleus. The relation antineutrinos vs Ng obtained in antineutrinos was used. For a given target nucleus this allows the selection of interactions occurring at different impact parameters.

  5. BDNF Overexpression in the Ventral Tegmental Area Prolongs Social Defeat Stress-induced Cross-Sensitization to Amphetamine and Increases ΔFosB Expression in Mesocorticolimbic Regions of Rats

    OpenAIRE

    Wang, Junshi; Fanous, Sanya; Terwilliger, Ernest F.; Bass, Caroline E.; Hammer, Ronald P; Nikulina, Ella M

    2013-01-01

    Social defeat stress induces persistent cross-sensitization to psychostimulants, but the molecular mechanisms underlying the development of cross-sensitization remain unclear. One candidate is brain-derived neurotrophic factor (BDNF). The present research examined whether ventral tegmental area (VTA) BDNF overexpression would prolong the time course of cross-sensitization after a single social defeat stress, which normally produces transient cross-sensitization lasting

  6. J/$\\psi$ production in proton-nucleus and nucleus-nucleus interactions at the CERN SPS

    CERN Document Server

    Abreu, M C; Alexa, C; Arnaldi, R; Ataian, M R; Baglin, C; Baldit, A; Bedjidian, Marc; Beolè, S; Boldea, V; Bordalo, P; Borges, G; Bussière, A; Capelli, L; Castanier, C; Castor, J I; Chaurand, B; Chevrot, I; Cheynis, B; Chiavassa, E; Cicalò, C; Claudino, T; Comets, M P; Constans, N; Constantinescu, S; Cortese, P; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Ducroux, L; Espagnon, B; Fargeix, J; Force, P; Gallio, M; Gavrilov, Yu K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanian, H R; Hakobyan, R S; Haroutunian, R; Idzik, M; Jouan, D; Karavitcheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Macciotta, P; MacCormick, M; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prado da Silva, W L; Prino, F; Puddu, G; Quintans, C; Ramello, L; Ramos, S; Rato-Mendes, P; Riccati, L; Romana, A; Santos, H; Saturnini, P; Scalas, E; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, F; Silva, S; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, Ermanno; Villatte, L; Willis, N

    2002-01-01

    The NA38 and NA50 experiments at the CERN SPS have measured charmonium production in different colliding systems with the aim of observing a phase transition from ordinary hadronic matter towards a state in which quarks and gluons are deconfined (quark-gluon plasma, QGP). This experimental research is based on the prediction that the J/ psi yield should be suppressed in deconfined matter. The analysis of the data collected by the NA50 experiment with Pb-Pb collisions at 158 GeV/c per nucleon shows that the J/ psi is anomalously suppressed with respect to the pattern observed in proton-nucleus and light ion reactions. (9 refs).

  7. Effects of Ascorbic Acid on the Amplitude of Ventral Tegmental Area Field Action Potential in Morphine-Exposed Rats (An Electrophysiology Study

    Directory of Open Access Journals (Sweden)

    K Saadipour

    2010-07-01

    Full Text Available Introduction & Objective: Evidences have indicated that the Ventral Tegmental Area (VTA is the major source of dopamine (DA neurons projecting to cortical and limbic regions involved in cognitive and motivational aspects of addiction. Also, studies have indicated that the Ascorbic acid (vitamin C can reduce the dependency symptoms of opioids such as morphine via effect of activity on dopaminergic neuron in VTA. For this reason, the aim of this study was to assess the effects of ascorbic acid on the amplitude of Ventral Tegmental Area field action potential in morphine-exposed rats. Materials & Methods: Forty male Wistar’s rats were used in this experimental study conducted at Yasuj University of Medical Sciences in 2010. Animals were randomly divided into four groups after electrode implantation and recovery period: 1. No- Vit C and No-Addicted group (nVitC.nA 2. Vit C and No-Addicted group (VitC.nA 3. No- Vit C and Addicted group (nVitCA 4.Vit C and Addicted (VitC.A, The Vit C groups received 500 mg/kg of Vit C during 20 days. For addicted groups morphine was administrated once daily for 20 days. In the 20th day, the field potential recording was accomplished. Two-way ANOVA was used for data analysis followed by the Tukey test for post hoc analysis. Results were considered significant at P < 0.05. Results: This study shows the exposure to morphine declined the power of Delta and Beta bands (p<0.05 and Vit C solely enhance power of Theta and Beta (p<0.05, p<0.001 in VTA nuclei. Furthermore, Vit C could alter power of some bands which were affected by morphine. Therefore it seems that Vit C has an increasing effects on them (p<0.05. Conclusion: Although the effect of Vit C on power of the VTA bands is not well known, but it is supposed that this phenomenon can be related to alteration in activity of dopaminergic neuron in the brain.

  8. Meson-nucleus potentials and the search for meson-nucleus bound states

    Science.gov (United States)

    Metag, V.; Nanova, M.; Paryev, E. Ya.

    2017-11-01

    Recent experiments studying the meson-nucleus interaction to extract meson-nucleus potentials are reviewed. The real part of the potentials quantifies whether the interaction is attractive or repulsive while the imaginary part describes the meson absorption in nuclei. The review is focused on mesons which are sufficiently long-lived to potentially form meson-nucleus quasi-bound states. The presentation is confined to meson production off nuclei in photon-, pion-, proton-, and light-ion induced reactions and heavy-ion collisions at energies near the production threshold. Tools to extract the potential parameters are presented. In most cases, the real part of the potential is determined by comparing measured meson momentum distributions or excitation functions with collision model or transport model calculations. The imaginary part is extracted from transparency ratio measurements. Results on K+ ,K0 ,K- , η ,η‧ , ω, and ϕ mesons are presented and compared with theoretical predictions. The interaction of K+ and K0 mesons with nuclei is found to be weakly repulsive, while the K- , η ,η‧ , ω and ϕ meson-nucleus potentials are attractive, however, with widely different strengths. Because of meson absorption in the nuclear medium the imaginary parts of the meson-nucleus potentials are all negative, again with a large spread. An outlook on planned experiments in the charm sector is given. In view of the determined potential parameters, the criteria and chances for experimentally observing meson-nucleus quasi-bound states are discussed. The most promising candidates appear to be the η and η‧ mesons.

  9. Aspects of Coulomb dissociation and interference in peripheral nucleus-nucleus collisions

    Energy Technology Data Exchange (ETDEWEB)

    Nystrand, Joakim; Baltz, Anthony; Klein, Spencer R.

    2001-10-21

    Coherent vector meson production in peripheral nucleus-nucleus collisions is discussed. These interactions may occur for impact parameters much larger than the sum of the nuclear radii. Since the vector meson production is always localized to one of the nuclei, the system acts as a two-source interferometer in the transverse plane. By tagging the outgoing nuclei for Coulomb dissociation it is possible to obtain a measure of the impact parameter and thus the source separation in the interferometer. This is of particular interest since the life-time of the vector mesons are generally much shorter than the impact parameters of the collisions.

  10. Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies.

    Science.gov (United States)

    Bergamini, Giorgio; Sigrist, Hannes; Ferger, Boris; Singewald, Nicolas; Seifritz, Erich; Pryce, Christopher R

    2016-10-01

    Dopamine (DA) neurotransmission, particularly the ventral tegmental area-nucleus accumbens (VTA-NAcc) projection, underlies reward and aversion processing, and deficient DA function could underlie motivational impairments in psychiatric disorders. 6-hydroxydopamine (6-OHDA) injection is an established method for chronic DA depletion, principally applied in rat to study NAcc DA regulation of reward motivation. Given the increasing focus on studying environmental and genetic regulation of DA function in mouse models, it is important to establish the effects of 6-OHDA DA depletion in mice, in terms of reward and aversion processing. This mouse study investigated effects of 6-OHDA-induced NAcc DA depletion using the operant behavioural test battery of progressive ratio schedule (PRS), learned non-reward (LNR), learned helplessness (LH), treadmill, and in addition Pavlovian fear conditioning. 6-OHDA NAcc DA depletion, confirmed by ex vivo HPLC-ED, reduced operant responding: for gustatory reward under effortful conditions in the PRS test; to a stimulus recently associated with gustatory non-reward in the LNR test; to escape footshock recently experienced as uncontrollable in the LH test; and to avoid footshock by physical effort in the treadmill test. Evidence for specificity of effects to NAcc DA was provided by lack of effect of medial prefrontal cortex DA depletion in the LNR and LH tests. These findings add significantly to the evidence that NAcc DA is a major regulator of behavioural responding, particularly at the motivational level, to both reward and aversion. They demonstrate the suitability of mouse models for translational study of causation and reversal of pathophysiological DA function underlying motivation psychopathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Ethanol is self-administered into the nucleus accumbens shell, but not the core: evidence of genetic sensitivity.

    Science.gov (United States)

    Engleman, Eric A; Ding, Zheng-Ming; Oster, Scott M; Toalston, Jamie E; Bell, Richard L; Murphy, James M; McBride, William J; Rodd, Zachary A

    2009-12-01

    A previous study indicated that selectively bred alcohol-preferring (P) rats self-administered ethanol (EtOH) directly into the posterior ventral tegmental area at lower concentrations than Wistar rats. The present study was undertaken to determine involvement of the nucleus accumbens (Acb) with EtOH reinforcement, and a relationship between genetic selection for high alcohol preference and sensitivity of the Acb to the reinforcing effects of EtOH. Adult P and Wistar rats were assigned to groups that self-infused 0 to 300 mg% EtOH into the Acb shell (AcbSh) or Acb Core (AcbC). Rats were placed into 2-lever (active and inactive) operant chambers and given EtOH for the first 4 sessions (acquisition), artificial cerebrospinal fluid (aCSF) for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the active lever produced a 100-nl injection of the infusate. Alcohol-preferring rats self-infused 75 to 300 mg% EtOH, whereas Wistar rats reliably self-infused 100 and 300 mg% EtOH into the AcbSh. Both P and Wistar rats reduced responding on the active lever when aCSF was substituted for EtOH, and reinstated responding in session 7 when EtOH was restored. EtOH was not self-infused into the AcbC by P or Wistar rats. The present results indicate that the AcbSh, but not AcbC, is a neuroanatomical structure that mediates the reinforcing actions of EtOH. The data also suggest that, compared to Wistar rats, the AcbSh of P rats is more sensitive to the reinforcing effects of EtOH.

  12. Acute Ethanol Administration Upregulates Synaptic α4-Subunit of Neuronal Nicotinic Acetylcholine Receptors within the Nucleus Accumbens and Amygdala

    Directory of Open Access Journals (Sweden)

    Josephine R. Tarren

    2017-10-01

    Full Text Available Alcohol and nicotine are two of the most frequently abused drugs, with their comorbidity well described. Previous data show that chronic exposure to nicotine upregulates high-affinity nicotinic acetylcholine receptors (nAChRs in several brain areas. Effects of ethanol on specific brain nAChR subtypes within the mesolimbic dopaminergic (DA pathway may be a key element in the comorbidity of ethanol and nicotine. However, it is unknown how alcohol affects the abundance of these receptor proteins. In the present study, we measured the effect of acute binge ethanol on nAChR α4 subunit levels in the prefrontal cortex (PFC, nucleus accumbens (NAc, ventral tegmental area (VTA, and amygdala (Amg by western blot analysis using a knock-in mouse line, generated with a normally functioning α4 nAChR subunit tagged with yellow fluorescent protein (YFP. We observed a robust increase in α4-YFP subunit levels in the NAc and the Amg following acute ethanol, with no changes in the PFC and VTA. To further investigate whether this upregulation was mediated by increased local mRNA transcription, we quantified mRNA levels of the Chrna4 gene using qRT-PCR. We found no effect of ethanol on α4 mRNA expression, suggesting that the upregulation of α4 protein rather occurs post-translationally. The quantitative counting of YFP immunoreactive puncta further revealed that α4-YFP protein is upregulated in presynaptic boutons of the dopaminergic axons projecting to the shell and the core regions of the NAc as well as to the basolateral amygdala (BLA, but not to the central or lateral Amg. Together, our results demonstrate that a single exposure to binge ethanol upregulates level of synaptic α4∗ nAChRs in dopaminergic inputs to the NAc and BLA. This upregulation could be linked to the functional dysregulation of dopaminergic signalling observed during the development of alcohol dependence.

  13. The role of nucleus accumbens core/shell in sleep-wake regulation and their involvement in modafinil-induced arousal.

    Directory of Open Access Journals (Sweden)

    Mei-Hong Qiu

    Full Text Available BACKGROUND: We have previously shown that modafinil promotes wakefulness via dopamine receptor D(1 and D(2 receptors; however, the locus where dopamine acts has not been identified. We proposed that the nucleus accumbens (NAc that receives the ventral tegmental area dopamine inputs play an important role not only in reward and addiction but also in sleep-wake cycle and in mediating modafinil-induced arousal. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we further explored the role of NAc in sleep-wake cycle and sleep homeostasis by ablating the NAc core and shell, respectively, and examined arousal response following modafinil administration. We found that discrete NAc core and shell lesions produced 26.5% and 17.4% increase in total wakefulness per day, respectively, with sleep fragmentation and a reduced sleep rebound after a 6-hr sleep deprivation compared to control. Finally, NAc core but not shell lesions eliminated arousal effects of modafinil. CONCLUSIONS/SIGNIFICANCE: These results indicate that the NAc regulates sleep-wake behavior and mediates arousal effects of the midbrain dopamine system and stimulant modafinil.

  14. The Role of Nucleus Accumbens Core/Shell in Sleep-Wake Regulation and their Involvement in Modafinil-Induced Arousal

    Science.gov (United States)

    Qu, Wei-Min; Urade, Yoshihiro; Lu, Jun; Huang, Zhi-Li

    2012-01-01

    Background We have previously shown that modafinil promotes wakefulness via dopamine receptor D1 and D2 receptors; however, the locus where dopamine acts has not been identified. We proposed that the nucleus accumbens (NAc) that receives the ventral tegmental area dopamine inputs play an important role not only in reward and addiction but also in sleep-wake cycle and in mediating modafinil-induced arousal. Methodology/Principal Findings In the present study, we further explored the role of NAc in sleep-wake cycle and sleep homeostasis by ablating the NAc core and shell, respectively, and examined arousal response following modafinil administration. We found that discrete NAc core and shell lesions produced 26.5% and 17.4% increase in total wakefulness per day, respectively, with sleep fragmentation and a reduced sleep rebound after a 6-hr sleep deprivation compared to control. Finally, NAc core but not shell lesions eliminated arousal effects of modafinil. Conclusions/Significance These results indicate that the NAc regulates sleep-wake behavior and mediates arousal effects of the midbrain dopamine system and stimulant modafinil. PMID:23029032

  15. An exceptionally bright, compact starburst nucleus

    Science.gov (United States)

    Margon, Bruce; Anderson, Scott F.; Mateo, Mario; Fich, Michel; Massey, Philip

    1988-01-01

    Observations are reported of a remarkably bright (V about 13) starburst nucleus, 0833 + 652, which has been detected at radio, infrared, optical, ultraviolet, and X-ray wavelengths. Despite an observed flux at each of these wavelengths which is comparable to that of NGC 7714, often considered the 'prototypical' example of the starburst phenomenon, 0833 + 652 appears to be a previously uncataloged object. Its ease of detectability throughout the electromagnetic spectrum should make it useful for a variety of problems in the study of compact emission-line galaxies.

  16. Lectures on the theory of the nucleus

    CERN Document Server

    Sitenko, Aleksej Grigorevich

    1975-01-01

    Provides an advanced and up-to-date account of the theory of nuclear structure and discusses in considerable detail both the superfluid and collective models of the nucleus, in addition to earlier complementary models and theories. The book also examines other important topics such as the rotational and vibrational spectra of nuclei which have not previously been treated in such depth. To summarize, it covers a large amount of theoretical ground in one volume and attempts to fill a serious gap in the literature. Many problems are included

  17. Contemporary models of the atomic nucleus

    CERN Document Server

    Nemirovskii, P E

    2013-01-01

    Contemporary Models of the Atomic Nucleus discusses nuclear structure and properties, expounding contemporary theoretical concepts of the low-energy nuclear processes underlying in nuclear models. This book focuses on subjects such as the optical nuclear model, unified or collective model, and deuteron stripping reaction. Other topics discussed include the basic nuclear properties; shell model; theoretical analysis of the shell model; and radiative transitions and alpha-decay. The deuteron theory and the liquid drop nuclear model with its application to fission theory are also mentioned, but o

  18. Temporary inactivation of ventral tegmental area neurons with either muscimol or baclofen reversibly disrupts maternal behavior in rats through different underlying mechanisms.

    Science.gov (United States)

    Numan, Michael; Stolzenberg, Danielle S; Dellevigne, Amanda A; Correnti, Christina M; Numan, Marilyn J

    2009-08-01

    The purpose of this study was to examine the effects of inactivation of ventral tegmental area (VTA) projection neurons, while sparing fibers of passage, on maternal behavior in rats. Because VTA neurons contain GABA-A and GABA-B receptors, the effects of muscimol or baclofen were studied. Although bilateral injections of either drug into the VTA disrupted maternal behavior, it is likely that they did so through different underlying mechanisms. Muscimol disrupted both retrieval of pups and nursing behavior, while causing stereotyped motor activity. Baclofen disrupted retrieval behavior without affecting nursing behavior, and control injections of baclofen into the region dorsal to VTA were ineffective. The effects of VTA baclofen on maternal behavior are similar to the effects of interference with mesolimbic dopamine (DA) function. The case is made that muscimol probably caused a hyperexcitation of VTA DA neurons through a process of disinhibition. In contrast, baclofen may have depressed the activity of all VTA projection neurons, including VTA DA neurons. Baclofen is a promising tool to explore whether medial preoptic area neurons interact with VTA neurons to control active maternal responses. 2009 APA, all rights reserved

  19. Ghrelin receptor activation in the ventral tegmental area amplified instrumental responding but not the excitatory influence of Pavlovian stimuli on instrumental responding.

    Science.gov (United States)

    Sommer, Susanne; Hauber, Wolfgang

    2016-10-01

    Pavlovian stimuli predictive of food are able to amplify instrumental responding for food. This phenomenon termed Pavlovian-instrumental transfer (PIT) critically depends on intact VTA function and mesoaccumbens dopamine transmission. Considerable evidence suggests that food-predictive stimuli can enhance the release of ghrelin, an orexigen hormone that promotes food-directed responding. The ventral tegmental area (VTA) appears to be a key region through which stimulation of ghrelin receptors (GHS-R1A) invigorates food-directed responding, in part by activating the mesoaccumbens dopamine system. Thus, it is conceivable that stimulation of GHS-R1A in the VTA can amplify PIT, i.e. stimulus-elicited increase in lever pressing for food. Here we examined in rats the effects of VTA ghrelin microinfusion on PIT. Our results demonstrate that ghrelin microinfusion into the VTA failed to enhance PIT suggesting that VTA GHS-R1A stimulation was unable to enhance the motivational significance of food-predictive stimuli. Consistent with previous studies, our results further indicate that intra-VTA ghrelin microinfusion invigorated instrumental responding under a progressive ratio schedule. These data provide support to the notion that VTA GHS-R1A stimulation increases the tendency to work for food. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. N-methyl-D-aspartate receptors in the ventral tegmental area mediate the excitatory influence of Pavlovian stimuli on instrumental performance.

    Science.gov (United States)

    Sommer, Susanne; Hauber, Wolfgang

    2016-12-01

    Pavlovian stimuli predictive of food can markedly amplify instrumental responding for food. This effect is termed Pavlovian-instrumental transfer (PIT). The ventral tegmental area (VTA) plays a key role in mediating PIT, however, it is yet unknown whether N-methyl-D-aspartate (NMDA)-type glutamate receptors in the VTA are involved in PIT. Here, we examined the effects of an NMDA-receptor blockade in the VTA on PIT. Immediately prior to PIT testing, rats were subjected to intra-VTA infusions of vehicle or of the NMDA-receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5) (1, 5 µg/side). In rats that received AP-5 at the lower dose, the PIT effect was intact, i.e. presentation of the Pavlovian stimulus enhanced instrumental responding. By contrast, in rats that received AP-5 at the higher dose, the PIT effect was blocked. The data suggest that NMDA receptors in the VTA mediate the activating effects of Pavlovian stimuli on instrumental responding.

  1. Differential modulation of arcuate nucleus and mesolimbic gene expression levels by central leptin in rats on short-term high-fat high-sugar diet.

    Directory of Open Access Journals (Sweden)

    José K van den Heuvel

    Full Text Available OBJECTIVE: Leptin resistance is a common hallmark of obesity. Rats on a free-choice high-fat high-sugar (fcHFHS diet are resistant to peripherally administered leptin. The aim of this study was to investigate feeding responses to central leptin as well as the associated changes in mRNA levels in hypothalamic and mesolimbic brain areas. DESIGN AND METHODS: Rats on a CHOW or fcHFHS diet for 8 days received leptin or vehicle intracerebro(lateralventricularly (ICV and food intake was measured 5 h and 24 h later. Four days later, rats were sacrificed after ICV leptin or vehicle and mRNA levels were quantified for hypothalamic pro-opiomelanocortin (POMC and neuropeptide Y (NPY and for preproenkephalin (ppENK in nucleus accumbens and tyrosine hydroxylase (TH in ventral tegmental area (VTA. RESULTS: ICV leptin decreased caloric intake both in CHOW and fcHFHS rats. In fcHFHS, leptin preferentially decreased chow and fat intake. Leptin increased POMC and decreased NPY mRNA in CHOW, but not in fcHFHS rats. In CHOW rats, leptin had no effect on ppENK mRNA and decreased TH mRNA. In fcHFHS, leptin decreased ppENK mRNA and increased TH mRNA. CONCLUSION: Despite peripheral and arcuate leptin resistance, central leptin suppresses feeding in fcHFHS rats. As the VTA and nucleus accumbens are still responsive to leptin, these brain areas may therefore, at least partly, account for the leptin-induced feeding suppression in rats on a fcHFHS diet.

  2. Neurochemical organization of the nucleus paramedianus dorsalis in the human

    OpenAIRE

    Baizer, Joan S.; Baker, James F.; Haas, Kristin; Lima, Raquel

    2007-01-01

    We have characterized the neurochemical organization of a small brainstem nucleus in the human brain, the nucleus paramedianus dorsalis (PMD). PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla, and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (a...

  3. Nucleus and nucleus-cytoskeleton connections in 3D cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lingling, E-mail: liulingling2012@163.com; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Sun, Jinghui, E-mail: sunjhemail@163.com; Song, Guanbin, E-mail: song@cqu.edu.cn

    2016-10-15

    Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and review how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from receptors at

  4. Delta-nucleus dynamics: proceedings of symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P. (eds.)

    1983-10-01

    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta ..delta..(1232), has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe ..delta..-nucleus dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented. (WHK)

  5. Observation of the antimatter helium-4 nucleus.

    Science.gov (United States)

    2011-05-19

    High-energy nuclear collisions create an energy density similar to that of the Universe microseconds after the Big Bang; in both cases, matter and antimatter are formed with comparable abundance. However, the relatively short-lived expansion in nuclear collisions allows antimatter to decouple quickly from matter, and avoid annihilation. Thus, a high-energy accelerator of heavy nuclei provides an efficient means of producing and studying antimatter. The antimatter helium-4 nucleus (4He), also known as the anti-α (α), consists of two antiprotons and two antineutrons (baryon number B = -4). It has not been observed previously, although the α-particle was identified a century ago by Rutherford and is present in cosmic radiation at the ten per cent level. Antimatter nuclei with B antimatter nuclei and a benchmark for possible future observations of 4He in cosmic radiation.

  6. Calcium microdomains in mitochondria and nucleus.

    Science.gov (United States)

    Alonso, María Teresa; Villalobos, Carlos; Chamero, Pablo; Alvarez, Javier; García-Sancho, Javier

    2006-01-01

    Endomembranes modify the progression of the cytosolic Ca(2+) wave and contribute to generate Ca(2+) microdomains, both in the cytosol and inside the own organella. The concentration of Ca(2+) in the cytosol ([Ca(2+)](C)), the mitochondria ([Ca(2+)](M)) and the nucleus ([Ca(2+)](N)) are similar at rest, but may become very different during cell activation. Mitochondria avidly take up Ca(2+) from the high [Ca(2+)](C) microdomains generated during cell activation near Ca(2+) channels of the plasma membrane and/or the endomembranes and prevent propagation of the high Ca(2+) signal to the bulk cytosol. This shaping of [Ca(2+)](C) signaling is essential for independent regulation of compartmentalized cell functions. On the other hand, a high [Ca(2+)](M) signal is generated selectively in the mitochondria close to the active areas, which tunes up respiration to the increased local needs. The progression of the [Ca(2+)](C) signal to the nucleus may be dampened by mitochondria, the nuclear envelope or higher buffering power inside the nucleoplasm. On the other hand, selective [Ca(2+)](N) signals could be generated by direct release of stored Ca(2+) into the nucleoplasm. Ca(2+) release could even be restricted to subnuclear domains. Putative Ca(2+) stores include the nuclear envelope, their invaginations inside the nucleoplasm (nucleoplasmic reticulum) and nuclear microvesicles. Inositol trisphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate have all been reported to produce release of Ca(2+) into the nucleoplasm, but contribution of these mechanisms under physiological conditions is still uncertain.

  7. Experimental and phenomenological investigations of QCD matter in high-energy nucleus-nucleus collisions

    Energy Technology Data Exchange (ETDEWEB)

    Andronic, Anton

    2014-07-15

    This thesis is heterogeneous, comprising experimental papers at low energies (SIS-18 at GSI) and at the LHC, papers on phenomenology of high-energy nucleus-nucleus collisions, and papers on detectors. The overview covers the experimental papers and those on phenomenology. I have chosen to write it in a general manner, intended to be accessible to non-experts. It emphasizes recent measurements and their understanding at the LHC. The detector papers, which address many principle aspects of gaseous detectors, are summarized and placed in context in the review I co-wrote and which closes the stack. The detector papers included here are the outcome of an R and D program for the Transition Radiation Detector of ALICE.

  8. Dynamical and statistical aspects in nucleus-nucleus collisions around the Fermi energy

    Energy Technology Data Exchange (ETDEWEB)

    Tamain, B.; Bocage, F.; Bougault, R.; Brou, R. [Caen Univ., 14 (France). Lab. de Physique Corpusculaire; Assenard, M. [Centre National de la Recherche Scientifique, 44 - Nantes (France). Lab. de Physique Subatomique et des Technologies Associees; Auger, G.; Benlliure, J. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France); Bacri, C.O.; Borderie, B. [Paris-11 Univ., 91 - Orsay (France). Inst. de Physique Nucleaire; Bisquer, E. [Lyon-1 Univ., 69 - Villeurbanne (France). Inst. de Physique Nucleaire] [and others

    1997-12-31

    Nucleus-nucleus collisions at low incident energy are mainly governed by statistical dissipative processes, fusion and deep inelastic reactions being the most important ones. Conversely, in the relativistic energy regime, dynamical effects play a dominant role and one should apply a participant-spectator picture in order to understand the data. In between, the intermediate energy region is a transition one in which it is necessary to disentangle dynamics from statistical effects. Moreover, the Fermi energy region corresponds to available energies comparable with nuclear binding energies and one may except to observe phase transition effects. Experiments performed recently with 4{pi} devices have given quite new data and a much better insight into involved mechanisms and hot nuclear matter properties. INDRA data related to reaction mechanisms and multifragmentation are presented. (author) 53 refs.

  9. A versatile dielectron trigger for nucleon-nucleon and nucleus-nucleus collisions

    CERN Document Server

    Schicker, R; Tsertos, H

    1998-01-01

    A novel approach for a versatile first level dielectron trigger is presented. This trigger operates in the low multiplicity environment of nucleon-nucleon reactions as well as in the high multiplicity situation of nucleus-nucleus collisions. For optimal trigger performance, time of flight conditions for the two fastest particles of the event are combined with event multiplicity requirements. The dielectron trigger efficiency is given. The event reduction factor of such a trigger approach is studied for a low, a medium and a high multiplicity environment. The impact parameter dependence of the event reduction is given. The timing properties of the trigger signal are described. The losses due to deadtime are specified. Finally, the first level trigger rate is reported.

  10. Area-specific analysis of the distribution of hypothalamic neurons projecting to the rat ventral tegmental area, with special reference to the GABAergic and glutamatergic efferents

    Science.gov (United States)

    Kalló, Imre; Molnár, Csilla S.; Szöke, Sarolta; Fekete, Csaba; Hrabovszky, Erik; Liposits, Zsolt

    2015-01-01

    The ventral tegmental area (VTA) is a main regulator of reward and integrates a wide scale of hormonal and neuronal information. Feeding-, energy expenditure-, stress, adaptation- and reproduction-related hypothalamic signals are processed in the VTA and influence the reward processes. However, the neuroanatomical origin and chemical phenotype of neurons mediating these signals to the VTA have not been fully characterized. In this study we have systematically mapped hypothalamic neurons that project to the VTA using the retrograde tracer Choleratoxin B subunit (CTB) and analyzed their putative gamma-aminobutyric acid (GABA) and/or glutamate character with in situ hybridization in male rats. 23.93 ± 3.91% of hypothalamic neurons projecting to the VTA was found in preoptic and 76.27 ± 4.88% in anterior, tuberal and mammillary hypothalamic regions. Nearly half of the retrogradely-labeled neurons in the preoptic, and more than one third in the anterior, tuberal and mammillary hypothalamus appeared in medially located regions. The analyses of vesicular glutamate transporter 2 (VGLUT2) and glutamate decarboxylase 65 (GAD65) mRNA expression revealed both amino acid markers in different subsets of retrogradely-labeled hypothalamic neurons, typically with the predominance of the glutamatergic marker VGLUT2. About one tenth of CTB-IR neurons were GAD65-positive even in hypothalamic nuclei expressing primarily VGLUT2. Some regions were populated mostly by GAD65 mRNA-containing retrogradely-labeled neurons. These included the perifornical part of the lateral hypothalamus where 58.63 ± 19.04% of CTB-IR neurons were GABAergic. These results indicate that both the medial and lateral nuclear compartments of the hypothalamus provide substantial input to the VTA. Furthermore, colocalization studies revealed that these projections not only use glutamate but also GABA for neurotransmission. These GABAergic afferents may underlie important inhibitory mechanism to fine-tune the

  11. GABA Uptake Inhibition Reduces In Vivo Extraction Fraction in the Ventral Tegmental Area of Long Evans Rats Measured by Quantitative Microdialysis Under Transient Conditions.

    Science.gov (United States)

    Zandy, Shannon L; Gonzales, Rueben A

    2018-02-01

    Inhibitory signaling in the ventral tegmental area (VTA) is involved in the mechanism of action for many drugs of abuse. Although drugs of abuse have been shown to alter extracellular γ-aminobutyric acid (GABA) concentration in the VTA, knowledge on how uptake mechanisms are regulated in vivo is limited. Quantitative (no-net-flux) microdialysis is commonly used to examine the extracellular concentration and clearance of monoamine neurotransmitters, however it is unclear whether this method is sensitive to changes in clearance for amino acid neurotransmitters such as GABA. The purpose of this study was to determine whether changes in GABA uptake are reflected by in vivo extraction fraction within the VTA. Using quantitative (no-net-flux) microdialysis adapted for transient conditions, we examined the effects of local perfusion with the GABA uptake inhibitor, nipecotic acid, in the VTA of Long Evans rats. Basal extracellular GABA concentration and in vivo extraction fraction were 44.4 ± 1.9 nM (x-intercepts from 4 baseline regressions using a total of 24 rats) and 0.19 ± 0.01 (slopes from 4 baseline regressions using a total of 24 rats), respectively. Nipecotic acid (50 μM) significantly increased extracellular GABA concentration to 170 ± 4 nM and reduced in vivo extraction fraction to 0.112 ± 0.003. Extraction fraction returned to baseline following removal of nipecotic acid from the perfusate. Conventional microdialysis substantially underestimated the increase of extracellular GABA concentration due to nipecotic acid perfusion compared with that obtained from the quantitative analysis. Together, these results show that inhibiting GABA uptake mechanisms within the VTA alters in vivo extraction fraction measured using microdialysis and that in vivo extraction fraction may be an indirect measure of GABA clearance.

  12. New quasibound states of the compound nucleus in α -particle capture by the nucleus

    Science.gov (United States)

    Maydanyuk, Sergei P.; Zhang, Peng-Ming; Zou, Li-Ping

    2017-07-01

    We generalize the theory of nuclear decay and capture of Gamow that is based on tunneling through the barrier and internal oscillations inside the nucleus. In our formalism an additional factor is obtained, which describes distribution of the wave function of the the α particle inside the nuclear region. We discover new most stable states (called quasibound states) of the compound nucleus (CN) formed during the capture of α particle by the nucleus. With a simple example, we explain why these states cannot appear in traditional calculations of the α capture cross sections based on monotonic penetrabilities of a barrier, but they appear in a complete description of the evolution of the CN. Our result is obtained by a complete description of the CN evolution, which has the advantages of (1) a clear picture of the formation of the CN and its disintegration, (2) a detailed quantum description of the CN, (3) tests of the calculated amplitudes based on quantum mechanics (not realized in other approaches), and (4) high accuracy of calculations (not achieved in other approaches). These peculiarities are shown with the capture reaction of α +44Ca . We predict quasibound energy levels and determine fusion probabilities for this reaction. The difference between our approach and theory of quasistationary states with complex energies applied for the α capture is also discussed. We show (1) that theory does not provide calculations for the cross section of α capture (according to modern models of the α capture), in contrast with our formalism, and (2) these two approaches describe different states of the α capture (for the same α -nucleus potential).

  13. The Confined Hydrogen Atom with a Moving Nucleus

    Science.gov (United States)

    Fernandez, Francisco M.

    2010-01-01

    We study the hydrogen atom confined to a spherical box with impenetrable walls but, unlike earlier pedagogical articles on the subject, we assume that the nucleus also moves. We obtain the ground-state energy approximately by means of first-order perturbation theory and show that it is greater than that for the case in which the nucleus is clamped…

  14. Lateral geniculate nucleus histopathology in the rat experimental ...

    African Journals Online (AJOL)

    Although trypanosomosis has a well knownaetiology, histopathological studies on brain regions involved in the control of circadian rhythms are scanty. Lateral geniculate nucleus works in conjunction with the suprachiasmatic nucleus, the master circadian rhythm pacemaker, in regulating circadian rhythms. The purpose of ...

  15. Functional network inference of the suprachiasmatic nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel; St. John, Peter C.; Wang, Thomas J.; Bales, Benjamin B.; Doyle, Francis J.; Herzog, Erik D.; Petzold, Linda R.

    2016-04-04

    In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.

  16. Subthalamic nucleus detects unnatural android movement.

    Science.gov (United States)

    Ikeda, Takashi; Hirata, Masayuki; Kasaki, Masashi; Alimardani, Maryam; Matsushita, Kojiro; Yamamoto, Tomoyuki; Nishio, Shuichi; Ishiguro, Hiroshi

    2017-12-19

    An android, i.e., a realistic humanoid robot with human-like capabilities, may induce an uncanny feeling in human observers. The uncanny feeling about an android has two main causes: its appearance and movement. The uncanny feeling about an android increases when its appearance is almost human-like but its movement is not fully natural or comparable to human movement. Even if an android has human-like flexible joints, its slightly jerky movements cause a human observer to detect subtle unnaturalness in them. However, the neural mechanism underlying the detection of unnatural movements remains unclear. We conducted an fMRI experiment to compare the observation of an android and the observation of a human on which the android is modelled, and we found differences in the activation pattern of the brain regions that are responsible for the production of smooth and natural movement. More specifically, we found that the visual observation of the android, compared with that of the human model, caused greater activation in the subthalamic nucleus (STN). When the android's slightly jerky movements are visually observed, the STN detects their subtle unnaturalness. This finding suggests that the detection of unnatural movements is attributed to an error signal resulting from a mismatch between a visual input and an internal model for smooth movement.

  17. Control of nucleus accumbens activity with neurofeedback.

    Science.gov (United States)

    Greer, Stephanie M; Trujillo, Andrew J; Glover, Gary H; Knutson, Brian

    2014-08-01

    The nucleus accumbens (NAcc) plays critical roles in healthy motivation and learning, as well as in psychiatric disorders (including schizophrenia and attention deficit hyperactivity disorder). Thus, techniques that confer control of NAcc activity might inspire new therapeutic interventions. By providing second-to-second temporal resolution of activity in small subcortical regions, functional magnetic resonance imaging (fMRI) can resolve online changes in NAcc activity, which can then be presented as "neurofeedback." In an fMRI-based neurofeedback experiment designed to elicit NAcc activity, we found that subjects could increase their own NAcc activity, and that display of neurofeedback significantly enhanced their ability to do so. Subjects were not as capable of decreasing their NAcc activity, however, and enhanced control did not persist after subsequent removal of neurofeedback. Further analyses suggested that individuals who recruited positive aroused affect were better able to increase NAcc activity in response to neurofeedback, and that NAcc neurofeedback also elicited functionally correlated activity in the medial prefrontal cortex. Together, these findings suggest that humans can modulate their own NAcc activity and that fMRI-based neurofeedback may augment their efforts. The observed association between positive arousal and effective NAcc control further supports an anticipatory affect account of NAcc function. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Comparing Realistic Subthalamic Nucleus Neuron Models

    Science.gov (United States)

    Njap, Felix; Claussen, Jens C.; Moser, Andreas; Hofmann, Ulrich G.

    2011-06-01

    The mechanism of action of clinically effective electrical high frequency stimulation is still under debate. However, recent evidence points at the specific activation of GABA-ergic ion channels. Using a computational approach, we analyze temporal properties of the spike trains emitted by biologically realistic neurons of the subthalamic nucleus (STN) as a function of GABA-ergic synaptic input conductances. Our contribution is based on a model proposed by Rubin and Terman and exhibits a wide variety of different firing patterns, silent, low spiking, moderate spiking and intense spiking activity. We observed that most of the cells in our network turn to silent mode when we increase the GABAA input conductance above the threshold of 3.75 mS/cm2. On the other hand, insignificant changes in firing activity are observed when the input conductance is low or close to zero. We thus reproduce Rubin's model with vanishing synaptic conductances. To quantitatively compare spike trains from the original model with the modified model at different conductance levels, we apply four different (dis)similarity measures between them. We observe that Mahalanobis distance, Victor-Purpura metric, and Interspike Interval distribution are sensitive to different firing regimes, whereas Mutual Information seems undiscriminative for these functional changes.

  19. Parity Measurements in the 70Ga Nucleus

    Science.gov (United States)

    Venegas Vargas, D. C.; Haring-Kaye, R. A.; Jones, K. D.; Le, K. Q.; Harbin, B. L.; Döring, J.; Abromeit, B.; Dungan, R.; Lubna, R.; Tabor, S. L.; Tai, P.-L.; Tripati, Vandana; Vonmoss, J. M.; Morrow, S. I.

    2017-09-01

    The odd-odd 70Ga nucleus was studied at high spin after being produced at Florida State University using the 62Ni(14C,αpn) fusion-evaporation reaction at a beam energy of 50 MeV. The resulting γ rays were detected in coincidence using an array of Compton-suppressed Ge detectors consisting of three Clover detectors and seven single-crystal detectors. The linear polarizations of eight γ-ray transitions in 70Ga were measured by comparing their scattering yields within a Clover detector in the parallel and perpendicular directions relative to the beam axis, under the requirement that at least one other γ ray in 70Ga was recorded by a single-crystal detector in the array. As a result of these measurements, the parities of six states were confirmed and those of two other states were established for the first time based on a comparison of the experimental polarizations with the predicted ones determined from known spin assignments. The resulting level spectrum of 70Ga shows both similarities and differences with the predictions of previous shell-model calculations. This work was supported by the U.S. National Science Foundation and the Ohio Wesleyan University Summer Science Research Program.

  20. Restoring Segmental Biomechanics Through Nucleus Augmentation: An In Vitro Study.

    Science.gov (United States)

    Pelletier, Matthew H; Cohen, Charles S; Ducheyne, Paul; Walsh, William R

    2016-12-01

    In vitro biomechanical laboratory study. The purpose of this study is to evaluate a mechanical treatment to create a degenerative motion segment and the ability of nucleus augmentation to restore biomechanics. In cases with an intact annulus fibrosus, the replacement or augmentation of the nucleus pulposus alone may provide a less invasive option to restore normal biomechanics and disk height when compared with spinal fusion or total disk replacement. Laboratory testing allows these changes to be fully characterized. However, without preexisting pathology, nucleus augmentation therapies are difficult to evaluate in vitro. The present study evaluated pure moment bending and compressive biomechanics in 3 states (n=6): (1) intact, (2) after creep loading and nucleus disruption to induce degenerative biomechanical changes, and (3) after nucleus augmentation through an injectable polymer (DiscCell). Neutral zone and ROM were increased in all modes of bending after the degenerative treatment. The most sensitive mode of bending was lateral bending, with intact ROM (20.0±2.9 degrees) increased to 22.3±2.6 degrees after degenerative treatment and reduced to 18.4±1.6 degrees after injection of the polymer. All bending ROM and NZ changes induced by the degenerative treatment were reversed by nucleus augmentation. This material was shown to be effective at altering motion segment biomechanics and restoring disk height during time zero tests. This technique may provide a model to examine the time zero performance of a nucleus augmentation device/material.

  1. Quarkonium-nucleus bound states from lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Beane, S.  R. [Univ. of Washington, Seattle, WA (United States); Chang, E. [Univ. of Washington, Seattle, WA (United States); Cohen, S.  D. [Univ. of Washington, Seattle, WA (United States); Detmold, W. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lin, H. -W. [Univ. of Washington, Seattle, WA (United States); Orginos, K. [College of William and Mary, Williamsburg, VA (United States); Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Parreño, A. [Univ., de Barcelona, Marti Franques (Spain); Savage, M.  J. [Univ. of Washington, Seattle, WA (United States)

    2015-06-11

    Quarkonium-nucleus systems are composed of two interacting hadronic states without common valence quarks, which interact primarily through multi-gluon exchanges, realizing a color van der Waals force. We present lattice QCD calculations of the interactions of strange and charm quarkonia with light nuclei. Both the strangeonium-nucleus and charmonium-nucleus systems are found to be relatively deeply bound when the masses of the three light quarks are set equal to that of the physical strange quark. Extrapolation of these results to the physical light-quark masses suggests that the binding energy of charmonium to nuclear matter is B < 40 MeV.

  2. Changes in gene expression within the ventral tegmental area following repeated excessive binge-like alcohol drinking by alcohol-preferring (P) rats.

    Science.gov (United States)

    McBride, William J; Kimpel, Mark W; McClintick, Jeanette N; Ding, Zheng-Ming; Hauser, Sheketha R; Edenberg, Howard J; Bell, Richard L; Rodd, Zachary A

    2013-08-01

    The objective of this study was to detect changes in gene expression in the ventral tegmental area (VTA) following repeated excessive binge-like ('loss-of-control') alcohol drinking by alcohol-preferring (P) rats. Adult female P rats (n = 7) were given concurrent access to 10, 20, and 30% EtOH for 4 1-h sessions daily for 10 weeks followed by 2 cycles of 2 weeks of abstinence and 2 weeks of EtOH access. Rats were sacrificed by decapitation 3 h after the 4th daily EtOH-access session at the end of the second 2-week relapse period. A water-control group of female P rats (n = 8) was also sacrificed. RNA was prepared from micro-punch samples of the VTA from individual rats; analyses were conducted with Affymetrix Rat 230.2 GeneChips. Ethanol intakes were 1.2-1.7 g/kg per session, resulting in blood levels >200 mg% at the end of the 4th session. There were 211 unique named genes that significantly differed (FDR = 0.1) between the water and EtOH groups. Bioinformatics analyses indicated alterations in a) transcription factors that reduced excitation-coupled transcription and promoted excitotoxic neuronal damage involving clusters of genes associated with Nfkbia, Fos, and Srebf1, b) genes that reduced cholesterol and fatty acid synthesis, and increased protein degradation, and c) genes involved in cell-to-cell interactions and regulation of the actin cytoskeleton. Among the named genes, there were 62 genes that showed differences between alcohol-naïve P and non-preferring (NP) rats, with 43 of the genes changing toward NP-like expression levels following excessive binge-like drinking in the P rats. These genes are involved in a pro-inflammatory response, and enhanced response to glucocorticoids and steroid hormones. Overall, the results of this study indicate that the repeated excessive binge-like alcohol drinking can change the expression of genes that may alter neuronal function in several ways, some of which may be deleterious. Copyright © 2013 Elsevier Inc

  3. The nucleus retroambiguus control of respiration.

    Science.gov (United States)

    Subramanian, Hari H; Holstege, Gert

    2009-03-25

    The role of the nucleus retroambiguus (NRA) in the context of respiration control has been subject of debate for considerable time. To solve this problem, we chemically (using d, l-homocysteic acid) stimulated the NRA in unanesthetized precollicularly decerebrated cats and studied the respiratory effect via simultaneous measurement of tracheal pressure and electromyograms of diaphragm, internal intercostal (IIC), cricothyroid (CT), and external oblique abdominal (EO) muscles. NRA-stimulation 0-1 mm caudal to the obex resulted in recruitment of IIC muscle and reduction in respiratory frequency. NRA-stimulation 1-3 mm caudal to the obex produced vocalization along with CT activation and slight increase in tracheal pressure, but no change in respiratory frequency. NRA-stimulation 3-5 mm caudal to the obex produced CT muscle activation and an increase in respiratory frequency, but no vocalization. NRA-stimulation 5-8 mm caudal to the obex produced EO muscle activation and reduction in respiratory frequency. A change to the inspiratory effort was never observed, regardless of which NRA part was stimulated. The results demonstrate that NRA does not control eupneic inspiration but consists of topographically separate groups of premotor interneurons each producing detailed motor actions. These motor activities have in common that they require changes to eupneic breathing. Different combination of activation of these premotor neurons determines the final outcome, e.g., vocalization, vomiting, coughing, sneezing, mating posture, or child delivery. Higher brainstem regions such as the midbrain periaqueductal gray (PAG) decides which combination of NRA neurons are excited. In simple terms, the NRA is the piano, the PAG one of the piano players.

  4. Quantitative analysis of the fusion cross sections using different microscopic nucleus-nucleus interactions

    Energy Technology Data Exchange (ETDEWEB)

    Adel, A. [Cairo University, Physics Department, Faculty of Science, Giza (Egypt); Majmaah University, Physics Department, College of Science, Al-Zulfi (Saudi Arabia); Alharbi, T. [Majmaah University, Physics Department, College of Science, Al-Zulfi (Saudi Arabia)

    2017-01-15

    The fusion cross sections for reactions involving medium and heavy nucleus-nucleus systems are investigated near and above the Coulomb barrier using the one-dimensional barrier penetration model. The microscopic nuclear interaction potential is computed by four methods, namely: the double-folding model based on a realistic density-dependent M3Y NN interaction with a finite-range exchange part, the Skyrme energy density functional in the semiclassical extended Thomas-Fermi approximation, the generalized Proximity potential, and the Akyuez-Winther interaction. The comparison between the calculated and the measured values of the fusion excitation functions indicates that the calculations of the DFM give quite satisfactory agreement with the experimental data, being much better than the other methods. New parameterized forms for the fusion barrier heights and positions are presented. Furthermore, the effects of deformation and orientation degrees of freedom on the distribution of the Coulomb barrier characteristics as well as the fusion cross sections are studied for the reactions {sup 16}O + {sup 70}Ge and {sup 28}Si + {sup 100}Mo. The calculated values of the total fusion cross sections are compared with coupled channel calculations using the code CCFULL and compared with the experimental data. Our results reveal that the inclusion of deformations and orientation degrees of freedom improves the comparison with the experimental data. (orig.)

  5. Formation and identification of Centauro and Strangelets in nucleus- nucleus collisions at the LHC

    CERN Document Server

    Angelis, Aris L S; Bogolyubsky, M Yu; Filippov, S N; Gladysz-Dziadus, E; Kharlov, Yu V; Kurepin, A B; Maevskaya, A I; Mavromanolakis, G; Panagiotou, A D; Sadovsky, S A; Stefanski, P; Wlodarczyk, Z

    1999-01-01

    We present a phenomenological model for the formation and decay of a cosmic ray Centauro fireball in the baryon-rich projectile fragmentation rapidity region in nucleus-nucleus interactions. Our model naturally incorporates the $9 possibility of strangelet formation, Strangelets being conjectured to be the "strongly penetrating component" observed in hadron-rich cosmic ray events. Based on this model we have performed Monte-Carlo simulations to study the $9 Centauro and strangelet dynamic and kinematic characteristics in central Pb+Pb collisions at LHC energies, as well as their identification by the detector system CASTOR. CASTOR is being developed for the ALICE heavy ion experiment at $9 the LHC and will probe the very forward pseudorapidity region 5.6

  6. EOS: A time projection chamber for the study of nucleus-nucleus collisions at the Bevalac

    Energy Technology Data Exchange (ETDEWEB)

    Pugh, H.G.; Odyniec, G.; Rai, G.; Seidl, P.

    1986-12-01

    The conceptual design is presented for a detector to identify and measure (..delta..p/p approx. = 1%) most of the 200 or so mid-rapidity charged particles (p, d, t, /sup 3/He, /sup 4/He, ..pi../sup + -/, K/sup + -/) produced in each central nucleus-nucleus collision (Au + Au) at Bevalac energies, as well as K/sub 3//sup 0/ and ..lambda../sup 0/. The beam particles and heavy spectator fragments are excluded from the detection volume by means of a central vacuum pipe. Particle identification is achieved by a combination of dE/dx measurements in the TPC, and of time-of-flight measurements in a scintillator array. The TPC is single-ended and its end cap is entirely covered with cathode pads (about 25,000 pads and about 1000 anode wires). A non-uniform pad distribution is proposed to accommodate the high multiplicity of particles emitted at forward angles. The performance of the detector is assessed with regard to multihit capability, tracking, momentum resolution, particle identification, ..lambda../sup 0/ reconstruction, space charge effects, field non-uniformity, dynamic range, data acquisition rate, and data analysis rate. 72 refs., 48 figs., 11 tabs.

  7. Nucleus management in manual small incision cataract surgery by phacosection

    Directory of Open Access Journals (Sweden)

    Ravindra M

    2009-01-01

    Full Text Available Nucleus management is critical in manual small incision cataract surgery (MSICS, as the integrity of the tunnel, endothelium and posterior capsule needs to be respected. Several techniques of nucleus management are in vogue, depending upon the specific technique of MSICS. Nucleus can be removed in toto or bisected or trisected into smaller segments. The pressure in the eye can be maintained at the desired level with the use of an anterior chamber maintainer or kept at atmospheric levels. In MSICS, unlike phacoemulsification, there is no need to limit the size of the tunnel or restrain the size of capsulorrhexis. Large well-structured tunnels and larger capsulorrhexis provide better control on the surgical maneuvers. Safety and simplicity of MSICS has made it extremely popular. The purpose of this article is to describe nucleus management by phacosection in MSICS.

  8. Colour, albedo and nucleus size of Halley's comet

    Science.gov (United States)

    Cruikshank, D. P.; Tholen, D. J.; Hartmann, W. K.

    1985-01-01

    Photometry of Halley's comet in the B, J, V, and K broadband filters during a time when the coma was very weak and presumed to contribute negligibly to the broadband photometry is reported. The V-J and J-K colors suggest that the color of the nucleus of Halley's comet is similar to that of the D-type asteroids, which in turn suggests that the surface of the nucleus has an albedo less than 0.1.

  9. The TLC: A Novel Auditory Nucleus of the Mammalian Brain

    OpenAIRE

    Saldaña Fernández, Enrique; Viñuela, Antonio; Marshall, Allen F.; Fitzpatrick, Douglas C.; Aparicio Vaquero, María Auxiliadora

    2007-01-01

    [EN]We have identified a novel nucleus of the mammalian brain and termed it the tectal longitudinal column (TLC). Basic histologic stains, tract-tracing techniques and three-dimensional reconstructions reveal that the rat TLC is a narrow, elongated structure spanning themidbrain tectum longitudinally. This paired nucleus is located close to the midline, immediately dorsal to the periaqueductal gray matter.It occupies what has traditionally been considered the most medial region of the deep su...

  10. Calcium-permeable AMPA receptors in the VTA and nucleus accumbens after cocaine exposure: When, how and why?

    Directory of Open Access Journals (Sweden)

    Marina E Wolf

    2012-06-01

    Full Text Available In animal models of drug addiction, cocaine exposure has been shown to increase levels of calcium-permeable AMPA receptors (CP-AMPARs in two brain regions that are critical for motivation and reward - the ventral tegmental area (VTA and the nucleus accumbens (NAc. This review compares CP-AMPAR plasticity in the two brain regions and addresses its functional significance. In VTA dopamine neurons, cocaine exposure results in synaptic insertion of high conductance CP-AMPARs in exchange for lower conductance calcium-impermeable AMPARs (CI-AMPARs. This plasticity is rapid (hours, GluA2-dependent, and can be observed with a single cocaine injection. In addition to strengthening synapses and altering Ca2+ signaling, CP-AMPAR insertion affects subsequent induction of plasticity at VTA synapses. However, CP-AMPAR insertion is unlikely to mediate the increased dopamine cell activity that occurs during early withdrawal from cocaine exposure. Within the VTA, the group I metabotropic glutamate receptor mGluR1 exerts a negative influence on CP-AMPAR accumulation. Acutely, mGluR1 stimulation elicits a form of LTD resulting from CP-AMPAR removal and CI-AMPAR insertion. In medium spiny neurons (MSNs of the NAc, extended access cocaine self-administration is required to increase CP-AMPAR levels. This is first detected after approximately a month of withdrawal and then persists. Once present in NAc synapses, CP-AMPARs mediate the expression of incubation of cue-induced cocaine craving. The mechanism of their accumulation may be GluA1-dependent, which differs from that observed in the VTA. However, similar to VTA, mGluR1 stimulation removes CP-AMPARs from MSN synapses. Loss of mGluR1 tone during cocaine withdrawal may contribute to CP-AMPAR accumulation in the NAc. Thus, results in both brain regions point to the possibility of using positive modulators of mGluR1 as a treatment for cocaine addiction.

  11. Study of high energy densities over extended nuclear volumes via nucleus-nucleus collisions at the SPS

    CERN Multimedia

    2002-01-01

    This experiment examines in detail the characteristics of ultra-relativistic nucleus-nucleus interactions using $^{16}$O beams of 200 GeV/A from the SPS. The experiment combines 4$\\pi$ calorimeter coverage with measurements of inclusive particle spectra, two-particle correlations, low and high-mass lepton pairs and photons. A multiwire active target allows maximum interaction rates with a minimum of secondary interactions. Additional data are taken with an emulsion target.

  12. Alterations of emotion, cognition and firing activity of the basolateral nucleus of the amygdala after partial bilateral lesions of the nigrostriatal pathway in rats.

    Science.gov (United States)

    Chen, Li; Liu, Jian; Zhang, Qiao Jun; Feng, Jian Jun; Gui, Zhen Hua; Ali, Umar; Wang, Yong; Fan, Ling Ling; Hou, Chen; Wang, Tao

    2011-07-15

    Although increasing evidence indicates that psychiatric symptoms are crucial characteristic of the early stage of Parkinson's disease (PD) and precede motor impairments, the neuronal firing activity of the basolateral nucleus of the amygdala (BLA) in the psychiatric symptom of PD and the involved mechanism are still unclear. In the present study, we examined the changes in emotional and cognitive tests not focused on motor fluency and firing activity of projection neurons in the BLA rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum, and the effects of apomorphine and the medial prefrontal cortex (mPFC) on these changes. Injection of 6-OHDA (10.5 μg) into the dorsal striatum produced 18-22% and 26-30% loss of tyrosine hydroxylase immunoreactive neurons in the ventral tegmental area and substantia nigra pars compacta of rats, respectively. The striatal lesions induced anxiety-like responses in the rats but did not result in depressive-like behavior or cognitive impairments. In the lesioned rats, the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and the firing pattern of BLA projection neurons was not changed. No significant differences were observed either in behaviors or firing activity of BLA projection neurons by further ibotenic acid lesions of the mPFC in the lesioned rats. Systemic administration of cumulative apomorphine (10-160 μg/kg) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA-lesioned and combined 6-OHDA- and mPFC-lesioned rats, but the latter needed more apomorphine stimulation. These data suggest that the anxiety in early stage of PD is possibly related to the decrease in firing activity of BLA projection neurons, which may be regulated by the activation of dopamine receptor in the mPFC. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Fluctuations and correlations in nucleus-nucleus collisions within transport approaches

    Energy Technology Data Exchange (ETDEWEB)

    Konchakovski, Volodymyr P.

    2009-10-01

    The current thesis is devoted to a systematic study of fluctuations and correlations in heavy-ion collisions, which might be considered as probes for the phase transition and the critical point in the phase diagram, within the Hadron-String- Dynamics (HSD) microscopic transport approach. This is a powerful tool to study nucleus-nucleus collisions and allows to completely simulate experimental collisions on an event-by-event basis. Thus, the transport model has been used to study fluctuations and correlations including the influence of experimental acceptance as well as centrality, system size and collision energy. The comparison to experimental data can separate the effects induced by a phase transition since there is no phase transition in the HSD version used here. Firstly the centrality dependence of multiplicity fluctuations has been studied. Different centrality selections have been performed in the analysis in correspondence to the experimental situation. For the fixed target experiment NA49 events with fixed numbers of the projectile participants have been studied while in the collider experiment PHENIX centrality classes of events have been defined by the multiplicity in certain phase space region. A decrease of participant number fluctuations (and thus volume fluctuations) in more central collisions for both experiments has been obtained. Another area of this work addresses to transport model calculations of multiplicity fluctuations in nucleus-nucleus collisions as a function of colliding energy and system size. This study is in full correspondence to the experimental program of the NA61 Collaboration at the SPS. Central C+C, S+S, In+In, and Pb+Pb nuclear collisions at Elab = 10, 20, 30, 40, 80, 158 AGeV have been investigated. The expected enhanced fluctuations - attributed to the critical point and phase transition - can be observed experimentally on top of a monotonic and smooth 'hadronic background'. These findings should be helpful for the

  14. PREFACE: 11th International Conference on Nucleus-Nucleus Collisions (NN2012)

    Science.gov (United States)

    Li, Bao-An; Natowitz, Joseph B.

    2013-03-01

    The 11th International Conference on Nucleus-Nucleus Collisions (NN2012) was held from 27 May to 1 June 2012, in San Antonio, Texas, USA. It was jointly organized and hosted by The Cyclotron Institute at Texas A&M University, College Station and The Department of Physics and Astronomy at Texas A&M University-Commerce. Among the approximately 300 participants were a large number of graduate students and post-doctoral fellows. The Keynote Talk of the conference, 'The State of Affairs of Present and Future Nucleus-Nucleus Collision Science', was given by Dr Robert Tribble, University Distinguished Professor and Director of the TAMU Cyclotron Institute. During the conference a very well-received public lecture on neutrino astronomy, 'The ICEcube project', was given by Dr Francis Halzen, Hilldale and Gregory Breit Distinguished Professor at the University of Wisconsin, Madison. The Scientific program continued in the general spirit and intention of this conference series. As is typical of this conference a broad range of topics including fundamental areas of nuclear dynamics, structure, and applications were addressed in 42 plenary session talks, 150 parallel session talks, and 21 posters. The high quality of the work presented emphasized the vitality and relevance of the subject matter of this conference. Following the tradition, the NN2012 International Advisory Committee selected the host and site of the next conference in this series. The 12th International Conference on Nucleus-Nucleus Collisions (NN2015) will be held 21-26 June 2015 in Catania, Italy. It will be hosted by The INFN, Laboratori Nazionali del Sud, INFN, Catania and the Dipartimento di Fisica e Astronomia of the University of Catania. The NN2012 Proceedings contains the conference program and 165 articles organized into the following 10 sections 1. Heavy and Superheavy Elements 2. QCD and Hadron Physics 3. Relativistic Heavy-Ion Collisions 4. Nuclear Structure 5. Nuclear Energy and Applications of

  15. Heterogeneous calretinin expression in the avian cochlear nucleus angularis.

    Science.gov (United States)

    Bloom, S; Williams, A; MacLeod, K M

    2014-08-01

    Multiple calcium-binding proteins (CaBPs) are expressed at high levels and in complementary patterns in the auditory pathways of birds, mammals, and other vertebrates, but whether specific members of the CaBP family can be used to identify neuronal subpopulations is unclear. We used double immunofluorescence labeling of calretinin (CR) in combination with neuronal markers to investigate the distribution of CR-expressing neurons in brainstem sections of the cochlear nucleus in the chicken (Gallus gallus domesticus). While CR was homogeneously expressed in cochlear nucleus magnocellularis, CR expression was highly heterogeneous in cochlear nucleus angularis (NA), a nucleus with diverse cell types analogous in function to neurons in the mammalian ventral cochlear nucleus. To quantify the distribution of CR in the total NA cell population, we used antibodies against neuronal nuclear protein (NeuN), a postmitotic neuron-specific nuclear marker. In NA neurons, NeuN label was variably localized to the cell nucleus and the cytoplasm, and the intensity of NeuN immunoreactivity was inversely correlated with the intensity of CR immunoreactivity. The percentage of CR + neurons in NA increased from 31 % in embryonic (E)17/18 chicks, to 44 % around hatching (E21), to 51 % in postnatal day (P) 8 chicks. By P8, the distribution of CR + neurons was uniform, both rostrocaudal and in the tonotopic (dorsoventral) axis. Immunoreactivity for the voltage-gated potassium ion channel Kv1.1, used as a marker for physiological type, showed broad and heterogeneous postsynaptic expression in NA, but did not correlate with CR expression. These results suggest that CR may define a subpopulation of neurons within nucleus angularis.

  16. Calculated dynamical evolution of the nucleus of comet Hartley 2

    Science.gov (United States)

    Ksanfomality, Leonid

    2013-04-01

    The nucleus of comet Hartley 2 has a relatively regular dumbbell shape with unequal heads. The narrow part of elongated shape contains a relatively smooth region whose covering material is highly different in its shallow structure compared to other parts of this celestial body. The surface of crudely spherical parts of the nucleus is different from the surface of the "neck", which implies a hypothesis that the shape of the nucleus of Hartley 2 is indicative of destruction of this celestial body occurring in our days. The nucleus rotates around its axis passing through the center of mass, and centrifugal forces arise. This process is hindered by gravitation between parts of the nucleus and gradual slowing of rotation due to body lengthening because of the increase in the moment of inertia (proportional to R2) and due to friction losses in the neck material. We posed the task to determine centrifugal and gravitational forces in the neck (and, respectively, the strains of stretching and compression), the moment of inertia of the body and supply of its rotational energy E, the volume of the nucleus and its average density, and the position of the barycenter and center of rotation. It can be assumed that these forces cause slow but progressive lengthening of the neck which should eventually result in fragmentation of the nucleus. Centrifugal forces can be found as a result of summation of forces produced by parts of the body. According to the calculation model, the total stretching forces in the section passing through the narrowest cut of the neck are 1.21E6 N. The corresponding compression forces in the section passing through the narrow section are 1.04E6 N. The comparison of these values indicates a paradoxical result: stretching strains dominate in the neck, while compressions are dominant in the section passing through the common center of mass. The excess of stretching strains in the neck is 11%. The inference is as follows: the right part of the neck and the

  17. Qualitative analysis neurons in the adult human dentate nucleus

    Directory of Open Access Journals (Sweden)

    Marić Dušica

    2012-01-01

    Full Text Available Although many relevant findings regarding to the morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little qualitative information has been collected on neuronal morphology in the adult human dentate nucleus. The neurons were labelled by Golgi staining from thirty human cerebella, obtained from medico-legal forensic autopsies of adult human bodies and free of significant brain pathology. The human dentate neurons were qualitatively analyzed and these cells were classified into two main classes: the small and the large multipolar neurons. Considering the shape of the cell body, number of the primary dendrites, shape of the dendritic tree and their position within the dentate nucleus, three subclasses of the large multipolar neurons have been recognized. The classification of neurons from the human dentate nucleus has been qualitatively confirmed in fetuses and premature infants. This study represents the first qualitative analysis and classification of the large multipolar neurons in the dentate nucleus of the adult human.

  18. Classical cadherins control nucleus and centrosome position and cell polarity.

    Science.gov (United States)

    Dupin, Isabelle; Camand, Emeline; Etienne-Manneville, Sandrine

    2009-06-01

    Control of cell polarity is crucial during tissue morphogenesis and renewal, and depends on spatial cues provided by the extracellular environment. Using micropatterned substrates to impose reproducible cell-cell interactions, we show that in the absence of other polarizing cues, cell-cell contacts are the main regulator of nucleus and centrosome positioning, and intracellular polarized organization. In a variety of cell types, including astrocytes, epithelial cells, and endothelial cells, calcium-dependent cadherin-mediated cell-cell interactions induce nucleus and centrosome off-centering toward cell-cell contacts, and promote orientation of the nucleus-centrosome axis toward free cell edges. Nucleus and centrosome off-centering is controlled by N-cadherin through the regulation of cell interactions with the extracellular matrix, whereas the orientation of the nucleus-centrosome axis is determined by the geometry of N-cadherin-mediated contacts. Our results demonstrate that in addition to the specific function of E-cadherin in regulating baso-apical epithelial polarity, classical cadherins control cell polarization in otherwise nonpolarized cells.

  19. Cochlear nucleus whole mount explants promote the differentiation of neuronal stem cells from the cochlear nucleus in co-culture experiments.

    Science.gov (United States)

    Rak, Kristen; Völker, Johannes; Jürgens, Lukas; Völker, Christine; Frenz, Silke; Scherzad, Agmal; Schendzielorz, Philipp; Jablonka, Sibylle; Mlynski, Robert; Radeloff, Andreas; Hagen, Rudolf

    2015-08-07

    The cochlear nucleus is the first brainstem nucleus to receive sensory input from the cochlea. Depriving this nucleus of auditory input leads to cellular and molecular disorganization which may potentially be counteracted by the activation or application of stem cells. Neuronal stem cells (NSCs) have recently been identified in the neonatal cochlear nucleus and a persistent neurogenic niche was demonstrated in this brainstem nucleus until adulthood. The present work investigates whether the neurogenic environment of the cochlear nucleus can promote the survival of engrafted NSCs and whether cochlear nucleus-derived NSCs can differentiate into neurons and glia in brain tissue. Therefore, cochlear nucleus whole-mount explants were co-cultured with NSCs extracted from either the cochlear nucleus or the hippocampus and compared to a second environment using whole-mount explants from the hippocampus. Factors that are known to induce neuronal differentiation were also investigated in these NSC-explant experiments. NSCs derived from the cochlear nucleus engrafted in the brain tissue and differentiated into all cells of the neuronal lineage. Hippocampal NSCs also immigrated in cochlear nucleus explants and differentiated into neurons, astrocytes and oligodendrocytes. Laminin expression was up-regulated in the cochlear nucleus whole-mounts and regulated the in vitro differentiation of NSCs from the cochlear nucleus. These experiments confirm a neurogenic environment in the cochlear nucleus and the capacity of cochlear nucleus-derived NSCs to differentiate into neurons and glia. Consequently, the presented results provide a first step for the possible application of stem cells to repair the disorganization of the cochlear nucleus, which occurs after hearing loss. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Insulin induces calcium signals in the nucleus of rat hepatocytes.

    Science.gov (United States)

    Rodrigues, Michele A; Gomes, Dawidson A; Andrade, Viviane A; Leite, M Fatima; Nathanson, Michael H

    2008-11-01

    Insulin is an hepatic mitogen that promotes liver regeneration. Actions of insulin are mediated by the insulin receptor, which is a receptor tyrosine kinase. It is currently thought that signaling via the insulin receptor occurs at the plasma membrane, where it binds to insulin. Here we report that insulin induces calcium oscillations in isolated rat hepatocytes, and that these calcium signals depend upon activation of phospholipase C and the inositol 1,4,5-trisphosphate receptor, but not upon extracellular calcium. Furthermore, insulin-induced calcium signals occur in the nucleus, and are temporally associated with selective depletion of nuclear phosphatidylinositol bisphosphate and translocation of the insulin receptor to the nucleus. These findings suggest that the insulin receptor translocates to the nucleus to initiate nuclear, inositol 1,4,5-trisphosphate-mediated calcium signals in rat hepatocytes. This novel signaling mechanism may be responsible for insulin's effects on liver growth and regeneration.

  1. Evidence for involvement of the subcoeruleus nucleus and nucleus raphe magnus in urine storage and penile erection in decerebrate rats.

    Science.gov (United States)

    Sugaya, K; Ogawa, Y; Hatano, T; Koyama, Y; Miyazato, T; Oda, M

    1998-06-01

    Micturition and male sexual activity require the lower urinary tract to function. During the sexual act, micturition must be inhibited and urine stored in the bladder. We studied the role of the brainstem in relation to both micturition/urine storage and penile erection in rats. Wire electrodes were placed on the dorsal nerve of the penis and microelectrodes for stimulation were introduced into the brainstem in decerebrate male rats. Electrical stimulation was used to locate optimally responding sites by monitoring the isovolumetric intravesical pressure and intracavernous pressure. Electrical stimulation of the dorsal nerve of the penis, the subcoeruleus nucleus in the rostral pons, and the nucleus raphe magnus in the caudal pons increased intracavernous pressure, but inhibited rhythmic bladder contractions. Electrical stimulation of Barrington's nucleus (the pontine micturition center in the rat) in the rostral pons induced bladder contraction. Stimulation of the pontine reticular formation did not increase intracavernous pressure. Acute transection of the thoracic spinal cord eliminated rhythmic bladder contractions, but gave rise to sporadic increments of intracavernous pressure. This electrophysiological study demonstrated that the subcoeruleus nucleus and nucleus raphe magnus are involved in both urine storage and penile erection, and that their physiological functions are reciprocally controlled; so that erection leads to inhibition of micturition.

  2. Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Chao; Yang, Qiang [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhu, Meifeng [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Du, Lilong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhang, Jiamin [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ma, Xinlong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Xu, Baoshan, E-mail: xubaoshan99@126.com [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Wang, Lianyong, E-mail: wly@nankai.edu.cn [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2014-04-01

    Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus.

  3. Brain networks modulated by subthalamic nucleus deep brain stimulation.

    Science.gov (United States)

    Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

    2016-09-01

    Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The

  4. Final State Interactions Effects in Neutrino-Nucleus Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Golan, Tomasz [Univ. of Wroctaw (Poland); Juszczak, Cezary [Univ. of Wroctaw (Poland); Sobczyk, Jan T. [Fermi National Accelerator Laboratory (FNAL), Batavia, IL (United States)

    2012-07-01

    Final State Interactions effects are discussed in the context of Monte Carlo simulations of neutrino-nucleus interactions. A role of Formation Time is explained and several models describing this effect are compared. Various observables which are sensitive to FSI effects are reviewed including pion-nucleus interaction and hadron yields in backward hemisphere. NuWro Monte Carlo neutrino event generator is described and its ability to understand neutral current $\\pi^0$ production data in $\\sim 1$ GeV neutrino flux experiments is demonstrated.

  5. Intrinsically disordered proteins in the nucleus of human cells.

    Science.gov (United States)

    Frege, Telma; Uversky, Vladimir N

    2015-05-01

    Intrinsically disordered proteins are known to perform a variety of important functions such as macromolecular recognition, promiscuous binding, and signaling. They are crucial players in various cellular pathway and processes, where they often have key regulatory roles. Among vital cellular processes intimately linked to the intrinsically disordered proteins is transcription, an intricate biological performance predominantly developing inside the cell nucleus. With this work, we gathered information about proteins that exist in various compartments and sub-nuclear bodies of the nucleus of the human cells, with the goal of identifying which ones are highly disordered and which functions are ascribed to the disordered nuclear proteins.

  6. Formation and decay of a hot compound nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, B.V.; Dalmolin, F.T.; Dutra, M.; Santos, T.J., E-mail: brett@ita.br [Instituto Tecnologico de Aeronautica (ITA), Sao Jose dos Campos SP (Brazil); Souza, S.R. [Universidade Federal de Rio Grande do Sul (UFRS), Porto Alegre RS, (Brazil); Universidade Federal de Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Fisica; Donangelo, R. [Instituto de Fisica, Universidad de la Republica de Uruguay, Montevideo (Uruguay); Universidade Federal de Rio Grande do Sul (UFRS), Porto Alegre RS, (Brazil)

    2014-07-01

    The compound nucleus plays an important role in nuclear reactions over a wide range of projectile-target combinations and energies. The limits that angular momentum places on its formation and existence are, for the most part, well understood. The limits on its excitation energy are not as clear. Here we first analyze general geometrical and thermodynamical features of a hot compound nucleus. We then discuss the manners by which it can decay and close by speculating on the high energy limit to its formation and existence. (author)

  7. Recent Developments in Neutrino/Antineutrino-Nucleus Interactions

    Directory of Open Access Journals (Sweden)

    Jorge G. Morfín

    2012-01-01

    Full Text Available Recent experimental results and developments in the theoretical treatment of neutrino-nucleus interactions in the energy range of 1–10 GeV are discussed. Difficulties in extracting neutrino-nucleon cross sections from neutrino-nucleus scattering data are explained and significance of understanding nuclear effects for neutrino oscillation experiments is stressed. Detailed discussions of the status of two-body current contribution in the kinematic region dominated by quasielastic scattering and specific features of partonic nuclear effects in weak DIS scattering are presented.

  8. Recent Developments in Neutrino/Antineutrino-Nucleus Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Morfín, Jorge G.; Nieves, Juan; Sobczyk, Jan T.

    2012-01-01

    Recent experimental results and developments in the theoretical treatment of neutrino-nucleus interactions in the energy range of 1–10 GeV are discussed. Difficulties in extracting neutrino-nucleon cross sections from neutrino-nucleus scattering data are explained and significance of understanding nuclear effects for neutrino oscillation experiments is stressed. Detailed discussions of the status of two-body current contribution in the kinematic region dominated by quasielastic scattering and specific features of partonic nuclear effects in weak DIS scattering are presented.

  9. Nucleus geometry and mechanical properties of resistance spot ...

    Indian Academy of Sciences (India)

    show that nugget diameter, indentation depth and tensile load-bearing capacity are affected by weld parameters. Coating prevents full joining at low parameters. Microhardness increased in heat-affected zone and weld metal. Keywords. Automotive steels; resistance spot welding; mechanical properties; nucleus geometry.

  10. Study of the variability of the nucleus of Centaurus A.

    Science.gov (United States)

    Fernandes de Mello Rabaca, D.; Abraham, Z.

    1990-11-01

    ABSTRACT. This work consists in the study of the variability of the nucleus of the peculiar galaxy NGC 5128 (Centaurus A) at the radio continuum frequency of 43 GHz. The data were obtained with the 13.7 m itapetinga Radiotelescope. The radio source presents a pair of inner radio lobes and a compact variable nucleus. The observational technique used was scans through the inner radio lobes and the nucleus. The quasi- simultaneous measurements of the flux density of each source allowed us to derive accurately the relative flux between them, and to obtain the real variability of the nucleus. RESUMO. Este trabalho consiste no estudo da variabilidade do nucleo da galaxia peculiar NGC 5128 (Centaurus A) no de radio na de 43 GHz. Os dados foram obtidos com 0 Radiotelescopio do Itapetinga. A radio fonte apresenta um par de lobulos internos e um nucleo compacto variavel. A tetnica observacional utilizada foi a de varreduras passando pelos lobulos e pelo nucleo. As medidas quase simultaneas da densidade de fluxo de cada fonte permitiu obter precisa- mente 0 fluxo relativo entre elas e a variabilidade real do nucleo. Keq woit : GALAXIES-RADIO

  11. Deexcitation of superdeformed bands in the nucleus Tb-151

    NARCIS (Netherlands)

    Finck, C; Appelbe, D; Beck, FA; Byrski, T; Cullen, D; Curien, D; deFrance, G; Duchene, G; Erturk, S; Haas, B; Khadiri, N; Kharraja, B; Prevost, D; Rigollet, C; Stezowski, O; Twin, P; Vivien, JP; Zuber, K

    1997-01-01

    The aim of this work is to get more informations about the decay-out of superdeformed bands. One of the best candidates in the mass A similar or equal to 150 region for that kind of research is the nucleus Tb-151. From previous works, it has been established that the first excited band goes lower in

  12. Subthalamic nucleus stimulation reverses mediofrontal influence over decision threshold

    NARCIS (Netherlands)

    Cavanagh, J.F.; Wiecki, T.V.; Cohen, M.X.; Figueroa, C.M.; Samanta, J.; Sherman, S.J.; Frank, M.J.

    2011-01-01

    It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying

  13. Inelastic magnetic electron scattering form factors of the Mg nucleus

    Indian Academy of Sciences (India)

    states of the 26Mg nucleus have been studied using shell model calculations. The universal sd of the Wildenthal interaction, universal sd-shell interaction A, universal sd-shell interaction B, are used for the sd-shell orbits. Core polarization effects accord- ing to microscopic theory are taken into account by the excitations of ...

  14. Nuclear structure in odd-odd nucleus [sup 138]Pr

    Energy Technology Data Exchange (ETDEWEB)

    Rizzutto, M.A.; Cybulska, E.W.; Vanin, V.R.; Oliveira, J.R.B.; Emediato, L.G.R.; Ribas, R.V.; Seale, W.A.; Rao, M.N.; Medina, N.H.; Botelho, S.; Acquadro, J.C.; Lima, C.L. (Sao Paulo Univ., SP (Brazil). Lab. Pelletron)

    1992-12-01

    With the view of extending the systematics of odd-odd Pr nuclei toward the N=82 closed shell, high-spin states in [sup 138]Pr nucleus have been investigated with the [sup 128]Te([sup 14]N, 4n[gamma]) reaction. Configurations and spin assignments are suggested for three of the observed band-structures. (orig.).

  15. Sex hormone receptors are present in the human suprachiasmatic nucleus

    NARCIS (Netherlands)

    Kruijver, Frank P. M.; Swaab, Dick F.

    2002-01-01

    The suprachiasmatic nucleus (SCN) is the clock of the brain that orchestrates circadian and circannual biological rhythms, such as the rhythms of hormones, body temperature, sleep and mood. These rhythms are frequently disturbed in menopause and even more so in dementia and can be restored in

  16. KINEMATIC DETECTION OF THE DOUBLE NUCLEUS IN M31

    NARCIS (Netherlands)

    GERSSEN, J; KUIJKEN, K; MERRIFIELD, MR

    1995-01-01

    Using a spectrum obtained under moderate (similar to 1 arcsec) seeing, we show that the double nucleus in M31 produces a strong kinematic signature even though the individual components are not spatially resolved. The signature consists of a significant asymmetric wing in the stellar velocity

  17. CTP synthase forms cytoophidia in the cytoplasm and nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Gou, Ke-Mian [MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT (United Kingdom); State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193 (China); Chang, Chia-Chun [Institute of Biotechnology, National Taiwan University, Taipei, Taiwan, ROC (China); Shen, Qing-Ji [MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT (United Kingdom); Sung, Li-Ying, E-mail: liyingsung@ntu.edu.tw [Institute of Biotechnology, National Taiwan University, Taipei, Taiwan, ROC (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROC (China); Liu, Ji-Long, E-mail: jilong.liu@dpag.ox.ac.uk [MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT (United Kingdom)

    2014-04-15

    CTP synthase is an essential metabolic enzyme responsible for the de novo synthesis of CTP. Multiple studies have recently showed that CTP synthase protein molecules form filamentous structures termed cytoophidia or CTP synthase filaments in the cytoplasm of eukaryotic cells, as well as in bacteria. Here we report that CTP synthase can form cytoophidia not only in the cytoplasm, but also in the nucleus of eukaryotic cells. Both glutamine deprivation and glutamine analog treatment promote formation of cytoplasmic cytoophidia (C-cytoophidia) and nuclear cytoophidia (N-cytoophidia). N-cytoophidia are generally shorter and thinner than their cytoplasmic counterparts. In mammalian cells, both CTP synthase 1 and CTP synthase 2 can form cytoophidia. Using live imaging, we have observed that both C-cytoophidia and N-cytoophidia undergo multiple rounds of fusion upon glutamine analog treatment. Our study reveals the coexistence of cytoophidia in the cytoplasm and nucleus, therefore providing a good opportunity to investigate the intracellular compartmentation of CTP synthase. - Highlights: • CTP synthase forms cytoophidia not only in the cytoplasm but also in the nucleus. • Glutamine deprivation and Glutamine analogs promotes cytoophidium formation. • N-cytoophidia exhibit distinct morphology when compared to C-cytoophidia. • Both CTP synthase 1 and CTP synthase 2 form cytoophidia in mammalian cells. • Fusions of cytoophidia occur in the cytoplasm and nucleus.

  18. Calcium-regulated import of myosin IC into the nucleus.

    Science.gov (United States)

    Maly, Ivan V; Hofmann, Wilma A

    2016-06-01

    Myosin IC is a molecular motor involved in intracellular transport, cell motility, and transcription. Its mechanical properties are regulated by calcium via calmodulin binding, and its functions in the nucleus depend on import from the cytoplasm. The import has recently been shown to be mediated by the nuclear localization signal located within the calmodulin-binding domain. In the present paper, it is demonstrated that mutations in the calmodulin-binding sequence shift the intracellular distribution of myosin IC to the nucleus. The redistribution is displayed by isoform B, described originally as the "nuclear myosin," but is particularly pronounced with isoform C, the normally cytoplasmic isoform. Furthermore, experimental elevation of the intracellular calcium concentration induces a rapid import of myosin into the nucleus. The import is blocked by the importin β inhibitor importazole. These findings are consistent with a mechanism whereby calmodulin binding prevents recognition of the nuclear localization sequence by importin β, and the steric inhibition of import is released by cell signaling leading to the intracellular calcium elevation. The results establish a mechanistic connection between the calcium regulation of the motor function of myosin IC in the cytoplasm and the induction of its import into the nucleus. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Nitric oxide and reactive oxygen species in the nucleus revisited.

    Science.gov (United States)

    Provost, Chantale; Choufani, Faten; Avedanian, Levon; Bkaily, Ghassan; Gobeil, Fernand; Jacques, Danielle

    2010-03-01

    Recent work from our group showed that the nuclear envelope membranes contain several G protein-coupled receptors, including prostaglandin E2 (EP3R) and endothelin-1 (ET-1) receptors. Activation of EP3R increased endothelial nitric oxide synthase (eNOS) RNA expression in nuclei. eNOS and inducible NOS (iNOS) are reported to also be present at the nuclear level. Furthermore, reactive oxygen species (ROS) were also localized at the nuclear level. In this review, we show that stimulation with NO donor sodium nitroprusside results in an increase of intranuclear calcium that was dependent on guanylate cyclase activation, but independent of MAPK. This increase in nuclear calcium correlated with an increase in nuclear transcription of iNOS. H2O2 and ET-1 increase both cytosolic and nuclear ROS in human endocardial endothelial cells and in human aortic vascular smooth muscle cells. This increase in ROS levels by H2O2 and ET-1 was reversed by the antioxidant glutathione. In addition, our results strongly suggest that cytosolic signalization is not only transmitted to the nucleus but is also generated by the nucleus. Furthermore, we demonstrate that oxidative stress can be sensed by the nucleus. These results highly suggest that ROS formation is also generated directly by the nucleus and that free radicals may contribute to ET-1 regulation of nuclear Ca2+ homeostasis.

  20. Inclusive jet production in ultrarelativistic proton-nucleus collisions

    CERN Document Server

    Perepelitsa, Dennis

    High-$p_\\mathrm{T}$ processes in proton- and deuteron-nucleus collisions at TeV energies are the best presently available way to study the partonic structure of the nucleus in a high-density regime. Jet production over a wide range of phase space can significantly constrain the current knowledge of nuclear parton distribution functions (nPDFs), which are substantially less well understood than the corresponding PDFs in protons and which have only recently begun to be treated in a spatially-dependent way. An accurate knowledge of nPDFs is crucial for a definitive control of perturbative processes in a cold nuclear environment, since high-$p_\\mathrm{T}$ probes are used to quantitatively investigate the hot QCD matter created in ultrarelativistic nucleus-nucleus collisions. Furthermore, jets from low Bjorken-$x$ partons can probe the transition from the dilute to saturated nuclear regimes. Jet production is investigated in $d$+Au collisions at $\\sqrt{s} = 200$ GeV with the PHENIX detector at the Relativistic Hea...

  1. The human granulocyte nucleus: Unusual nuclear envelope and heterochromatin composition.

    Science.gov (United States)

    Olins, Ada L; Zwerger, Monika; Herrmann, Harald; Zentgraf, Hanswalter; Simon, Amos J; Monestier, Marc; Olins, Donald E

    2008-05-01

    The human blood granulocyte (neutrophil) is adapted to find and destroy infectious agents. The nucleus of the human neutrophil has a segmented appearance, consisting of a linear or branched array of three or four lobes. Adequate levels of lamin B receptor (LBR) are necessary for differentiation of the lobulated nucleus. The levels of other components of the nuclear envelope may also be important for nuclear shape determination. In the present study, immunostaining and immunoblotting procedures explored the levels of various components of the nuclear envelope and heterochromatin, comparing freshly isolated human neutrophils with granulocytic forms of HL-60 cells, a tissue culture model system. In comparison to granulocytic HL-60 cells, blood neutrophil nuclear envelopes contain low-to-negligible amounts of LBR, lamins A/C, B1 and B2, LAP2beta and emerin. Surprisingly, a "mitotic" chromosome marker, H3(S10)phos, is elevated in neutrophil nuclei, compared to granulocytic HL-60 cells. Furthermore, neutrophil nuclei appear to be more fragile to methanol fixation, than observed with granulocytic HL-60 cells. Thus, the human neutrophil nucleus appears to be highly specialized, possessing a paucity of nuclear envelope-stabilizing proteins. In consequence, the neutrophil nucleus appears to be very malleable, supporting rapid migration through tight tissue spaces.

  2. Cortically evoked potentials in the human subthalamic nucleus

    NARCIS (Netherlands)

    Zwartjes - de Klerk, D.G.M; Janssen, M.L.F; Heida, Tjitske; van Kranen-Mastenbroek, V.; Bour, L.; Temel, Y.; Visser-Vandewalle, V.; Martens, H.C.F.; Veltink, Petrus H.

    2013-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson’s disease (PD) patients. However, in a substantial number of patients the beneficial effects of STN DBS are overshadowed by psychiatric side effects. We hypothesize that stimulation of the STN motor

  3. Saturating Cronin effect in ultrarelativistic proton-nucleus collisions

    OpenAIRE

    Papp, Gabor; Levai, Peter; Fai, George

    1999-01-01

    Pion and photon production cross sections are analyzed in proton-proton and proton-nucleus collisions at energies 20 GeV < s^1/2 < 60 GeV. We separate the proton-proton and nuclear contributions to transverse-momentum broadening and suggest a new mechanism for the nuclear enhancement in the high transverse-momentum region.

  4. Red nucleus connectivity as revealed by constrained spherical deconvolution tractography.

    Science.gov (United States)

    Milardi, Demetrio; Cacciola, Alberto; Cutroneo, Giuseppina; Marino, Silvia; Irrera, Mariangela; Cacciola, Giorgio; Santoro, Giuseppe; Ciolli, Pietro; Anastasi, Giuseppe; Calabrò, Rocco Salvatore; Quartarone, Angelo

    2016-07-28

    Previous Diffusion Tensor Imaging studies have demonstrated that the human red nucleus is widely interconnected with sensory-motor and prefrontal cortices. In this study, we assessed red nucleus connectivity by using a multi-tensor model called non- negative Constrained Spherical Deconvolution (CSD), which is able to resolve more than one fiber orientation per voxel. Connections of the red nuclei of fifteen volunteers were studied at 3T using CSD axonal tracking. We found significant connectivity between RN and the following cortical and subcortical areas: cerebellar cortex, thalamus, paracentral lobule, postcentral gyrus, precentral gyrus, superior frontal gyrus and dentate nucleus. We confirmed that red nucleus is tightly linked with the cerebral cortex and has dense subcortical connections with thalamus and cerebellar cortex. These findings may be useful in a clinical context considering that RN is involved in motor control and it is known to have potential to compensate for injury of the corticospinal tract. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Glucocorticoids suppress vasopressin gene expression in human suprachiasmatic nucleus.

    NARCIS (Netherlands)

    Liu, R.-Y.; Unmehopa, U.A.; Zhou, J.-N.; Swaab, D.F.

    2006-01-01

    Sleep impairment is one of the major side effects of glucocorticoid therapy. The mechanism responsible for this circadian disorder is unknown, but alterations in the suprachiasmatic nucleus (SCN), the biological clock of the human brain, are presumed to play a major role. In the present study, the

  6. Glucocorticoids suppress vasopressin gene expression in human suprachiasmatic nucleus

    NARCIS (Netherlands)

    Liu, Rong-Yu; Unmehopa, Unga A.; Zhou, Jiang-Ning; Swaab, Dick F.

    2006-01-01

    Sleep impairment is one of the major side effects of glucocorticoid therapy. The mechanism responsible for this circadian disorder is unknown, but alterations in the suprachiasmatic nucleus (SCN), the biological clock of the human brain, are presumed to play a major role. In the present study, the

  7. Physical interrelation of volatile and refractories in a cometary nucleus

    Science.gov (United States)

    Fulle, Marco; Alice Team; Stern, Alan; CONSTERT Team; Kofman, Wlodek; COSIMA Team; Hilchenbach, Martin; GIADA Team; Rotundi, Alessandra; MIDAS Team; Bentley, Mark; MIRO Team; Hofstadter, Mark; OSIRIS Team; Sierks, Holger; ROSINA Team; Altwegg, Kathrin; RPC Team; Nilsson, Hans; Burch, James; Eriksson, Anders; Heinz-Glassmeier, Karl; Henri, Pierre; Carr, Christopher; RSI Team; Paetzold, Martin; , VIRTIS Team; Capaccioni, Fabrizio; Lander Team; Boehnhardt, Hermann; Bibring, Jean-Pierre; IDS Team; Gruen, Eberhard; Fulchignoni, Marcello; Weissman, Paul; Project Scientist Team; Taylor, Matt; Buratti, Bonnie; Altobelli, Nicolas; Choukroun, Mathieu; Ground-Based Observations Team; Snodgrass, Colin

    2016-10-01

    The Rosetta mission has been taking measurements of its target comet Comet 67P/Churyumov-Gerasimenko since early 2014 and will complete operations at the end of September 2016. The mission Science Management Plan, in 1994, laid out the the prime goals and themes of the mission. These five themes were: 1) To study the global characterisation of the Nuclues, the determination of the dynamics properties , surface morpholy and composition of the comet. 2) Examination of the Chemical, Mineralogical and isotopic compositions of volatiles and refractories in a cometary nucleus.3) Physical interrelation of volatile and refractories in a cometary nucleus4) Study the development of cometary activity and the process in the surface layer of the nucleus and in the inner coma5) The origins of comets, the relationship between cometary and interstellar material and the implications for the origin of the solar system,To cover all aspects of the Rosetta mission in this special Show case session, this abstracts is one of 5, with this particular presentation focusing on theme 3, in particular on a) The dust-to-gas ratio; b) distributed sources of volatiles; c) seasonal evolution of the dust size distribution.a) The dust-to-gas ratio has been provided by coma observations measuring the gas and dust loss rates from the nucleus surface. The ratio of these two loss rates provides a lower limit of the dust-to-gas ratio at the nucleus surface, since it does not take into account the largest chunks unable to leave the nucleus, or falling back due to the dominant gravity. We review the value inferred so far, its time evolution, and new techniques to directly measure it in the nucleus.b) Evidences offered by Rosetta observations of gas sublimating from dust particles are up to now faint. We report the few available observations and an estimate of the probable average water content in dust particles inferred by 3D gas-dynamical codes of 67P coma.c) The dust-size distribution tunes the sizes

  8. Structures and functions in the crowded nucleus: new biophysical insights

    Directory of Open Access Journals (Sweden)

    Ronald eHancock

    2014-09-01

    Full Text Available Concepts and methods from the physical sciences have catalysed remarkable progress in understanding the cell nucleus in recent years. To share this excitement with physicists and encourage their interest in this field, this review offers an overview of how the physics which underlies structures and functions in the nucleus is becoming more clear thanks to methods which have been developed to simulate and study macromolecules, polymers, and colloids. The environment in the nucleus is very crowded with macromolecules, making entropic (depletion forces major determinants of interactions. Simulation and experiments are consistent with their key role in forming membraneless compartments such as nucleoli, PML and Cajal bodies, and discrete territories for chromosomes. The chromosomes, giant linear polyelectrolyte polymers, exist in vivo in a state like a polymer melt. Looped conformations are predicted in crowded conditions, and have been confirmed experimentally and are central to the regulation of gene expression. Polymer theory has revealed how the chromosomes are so highly compacted in the nucleus, forming a crumpled globule with fractal properties which avoids knots and entanglements in DNA while allowing facile accessibility for its replication and transcription. Entropic repulsion between looped polymers can explain the confinement of each chromosome to a discrete region of the nucleus. Crowding and looping are predicted to facilitate finding the specific targets of factors which modulate activities of DNA. Simulation shows that entropic effects contribute to finding and repairing potentially lethal double-strand breaks in DNA by increasing the mobility of the broken ends, favouring their juxtaposition for repair. Signaling pathways are strongly influenced by crowding, which favours a processive mode of response (consecutive reactions without releasing substrates. This new information contributes to understanding the sometimes counter

  9. Cochlear nucleus neuron analysis in individuals with presbycusis.

    Science.gov (United States)

    Hinojosa, Raul; Nelson, Erik G

    2011-12-01

    The aim of this study was to analyze the cochlear nucleus neuron population in individuals with normal hearing and presbycusis. Retrospective study of archival human temporal bone and brain stem tissues. Using strict inclusion criteria, the temporal bones and cochlear nuclei from six normal hearing individuals and four individuals with presbycusis were selected for analysis. The spiral ganglion cell population, the cochlear nucleus neuron population, and the cell body size of the neurons were quantified in these cases. A relationship was not observed between age and the spiral ganglion cell population in the normal hearing group. Presbycusis subjects exhibited a reduced spiral ganglion cell population. The mean cochlear nucleus neuron population was observed to be significantly higher in the presbycusis group (mean ± standard deviation: 114,170 ± 10,570) compared to the normal hearing group (91,470 ± 9,510) (P = .019). This difference was predominantly the result of greater multipolar and granule cell neuron populations. Only the fusiform neuron type exhibited a significantly different mean cell body cross-sectional area between the normal hearing group (242 ± 27) and the presbycusis group (300 ± 37) (P = .033). This investigation is the first time, to our knowledge, that the populations of the eight neuron types in the cochlear nucleus have been quantified in both normal hearing individuals and individuals with presbycusis. The data support the concept that presbycusis is not an effect of aging alone but instead may be a condition that predisposes one to hearing loss with advancing age and is characterized by a congenitally elevated cochlear nucleus neuron population. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  10. DMPD: TGF-beta signaling from receptors to the nucleus. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10611754 TGF-beta signaling from receptors to the nucleus. Roberts AB. Microbes Inf...leus. PubmedID 10611754 Title TGF-beta signaling from receptors to the nucleus. Authors Roberts AB. Publicat

  11. IHW COMET HALLEY NEAR NUCLEUS IMAGE DATA, V2.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set presents images of the nucleus of comet 1P/Halley obtained by the various contributing observers of the International Halley Watch (IHW) Near-Nucleus...

  12. Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens

    NARCIS (Netherlands)

    van Dongen, Y.C.; Deniau, J.M.; Pennartz, C.M.A.; Galis-de Graaf, Y.; Voorn, P.; Thierry, A.M.; Groenewegen, H.J.

    2005-01-01

    The nucleus accumbens is thought to subserve different aspects of adaptive and emotional behaviors. The anatomical substrates for such actions are multiple, parallel ventral striatopallidal output circuits originating in the nucleus accumbens shell and core subregions. Several indirect ways of

  13. Projections from the raphe nuclei to the suprachiasmatic nucleus of the rat

    DEFF Research Database (Denmark)

    Hay-Schmidt, Anders; Vrang, N.; Larsen, P.J.

    2003-01-01

    Hypothalamus, Circadian rhythm, Serotonin, Nucleus, Neuronal connections, Phaseolus vulgaris-leucoagglutinin (PHA-L), Cholera toxin (ChB)......Hypothalamus, Circadian rhythm, Serotonin, Nucleus, Neuronal connections, Phaseolus vulgaris-leucoagglutinin (PHA-L), Cholera toxin (ChB)...

  14. Responses of primate caudal parabrachial nucleus and Kolliker-fuse nucleus neurons to whole body rotation

    Science.gov (United States)

    Balaban, Carey D.; McGee, David M.; Zhou, Jianxun; Scudder, Charles A.

    2002-01-01

    The caudal aspect of the parabrachial (PBN) and Kolliker-Fuse (KF) nuclei receive vestibular nuclear and visceral afferent information and are connected reciprocally with the spinal cord, hypothalamus, amygdala, and limbic cortex. Hence, they may be important sites of vestibulo-visceral integration, particularly for the development of affective responses to gravitoinertial challenges. Extracellular recordings were made from caudal PBN cells in three alert, adult female Macaca nemestrina through an implanted chamber. Sinusoidal and position trapezoid angular whole body rotation was delivered in yaw, roll, pitch, and vertical semicircular canal planes. Sites were confirmed histologically. Units that responded during rotation were located in lateral and medial PBN and KF caudal to the trochlear nerve at sites that were confirmed anatomically to receive superior vestibular nucleus afferents. Responses to whole-body angular rotation were modeled as a sum of three signals: angular velocity, a leaky integration of angular velocity, and vertical position. All neurons displayed angular velocity and integrated angular velocity sensitivity, but only 60% of the neurons were position-sensitive. These responses to vertical rotation could display symmetric, asymmetric, or fully rectified cosinusoidal spatial tuning about a best orientation in different cells. The spatial properties of velocity and integrated velocity and position responses were independent for all position-sensitive neurons; the angular velocity and integrated angular velocity signals showed independent spatial tuning in the position-insensitive neurons. Individual units showed one of three different orientations of their excitatory axis of velocity rotation sensitivity: vertical-plane-only responses, positive elevation responses (vertical plane plus ipsilateral yaw), and negative elevation axis responses (vertical plane plus negative yaw). The interactions between the velocity and integrated velocity components

  15. Regional Difference in Sex Steroid Action on Formation of Morphological Sex Differences in the Anteroventral Periventricular Nucleus and Principal Nucleus of the Bed Nucleus of the Stria Terminalis

    Science.gov (United States)

    Kanaya, Moeko; Tsuda, Mumeko C.; Sagoshi, Shoko; Nagata, Kazuyo; Morimoto, Chihiro; Tha Thu, Chaw Kyi; Toda, Katsumi; Kato, Shigeaki; Ogawa, Sonoko; Tsukahara, Shinji

    2014-01-01

    Sex steroid action is critical to form sexually dimorphic nuclei, although it is not fully understood. We previously reported that masculinization of the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), which is larger and has more neurons in males than in females, involves aromatized testosterone that acts via estrogen receptor-α (ERα), but not estrogen receptor-β (ERβ). Here, we examined sex steroid action on the formation of the anteroventral periventricular nucleus (AVPV) that is larger and has more neurons in females. Morphometrical analysis of transgenic mice lacking aromatase, ERα, or ERβ genes revealed that the volume and neuron number of the male AVPV were significantly increased by deletion of aromatase and ERα genes, but not the ERβ gene. We further examined the AVPV and BNSTp of androgen receptor knockout (ARKO) mice. The volume and neuron number of the male BNSTp were smaller in ARKO mice than those in wild-type mice, while no significant effect of ARKO was found on the AVPV and female BNSTp. We also examined aromatase, ERα, and AR mRNA levels in the AVPV and BNSTp of wild-type and ARKO mice on embryonic day (ED) 18 and postnatal day (PD) 4. AR mRNA in the BNSTp and AVPV of wild-type mice was not expressed on ED18 and emerged on PD4. In the AVPV, the aromatase mRNA level was higher on ED18, although the ERα mRNA level was higher on PD4 without any effect of AR gene deletion. Aromatase and ERα mRNA levels in the male BNSTp were significantly increased on PD4 by AR gene deletion. These results suggest that estradiol signaling via ERα during the perinatal period and testosterone signaling via AR during the postnatal period are required for masculinization of the BNSTp, whereas the former is sufficient to defeminize the AVPV. PMID:25398007

  16. Large contribution of virtual Delbrueck scattering to the emission of photons by relativistic nuclei in nucleus-nucleus and electron-nucleus collisions

    OpenAIRE

    Ginzburg, I. F.; Jentschura, U. D.; Serbo, V G

    2007-01-01

    Delbrueck scattering is an elastic scattering of a photon in the Coulomb field of a nucleus via a virtual electron loop. The contribution of this virtual subprocess to the emission of a photon in the collision of ultra-relativistic nuclei Z_1 Z_2 -> Z_1 Z_2 gamma is considered. We identify the incoming virtual photon as being generated by one of the relativistic nuclei involved in the binary collision and the scattered photon as being emitted in the process. The energy and angular distributio...

  17. File list: His.Neu.50.AllAg.Caudate_Nucleus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.50.AllAg.Caudate_Nucleus hg19 Histone Neural Caudate Nucleus SRX998285,SRX9...98283 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.50.AllAg.Caudate_Nucleus.bed ...

  18. File list: His.Neu.10.AllAg.Caudate_Nucleus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Caudate_Nucleus hg19 Histone Neural Caudate Nucleus SRX998285,SRX9...98283 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.10.AllAg.Caudate_Nucleus.bed ...

  19. File list: His.Neu.05.AllAg.Caudate_Nucleus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.05.AllAg.Caudate_Nucleus hg19 Histone Neural Caudate Nucleus SRX998283,SRX9...98285 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.05.AllAg.Caudate_Nucleus.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.20.AllAg.Caudate_Nucleus hg19 All antigens Neural Caudate Nucleus SRX998285...,SRX998283 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.20.AllAg.Caudate_Nucleus.bed ...

  1. File list: ALL.Neu.50.AllAg.Caudate_Nucleus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.50.AllAg.Caudate_Nucleus hg19 All antigens Neural Caudate Nucleus SRX998285...,SRX998283 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.50.AllAg.Caudate_Nucleus.bed ...

  2. File list: ALL.Neu.10.AllAg.Caudate_Nucleus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.10.AllAg.Caudate_Nucleus hg19 All antigens Neural Caudate Nucleus SRX998285...,SRX998283 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.10.AllAg.Caudate_Nucleus.bed ...

  3. File list: His.Neu.20.AllAg.Caudate_Nucleus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.20.AllAg.Caudate_Nucleus hg19 Histone Neural Caudate Nucleus SRX998285,SRX9...98283 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.20.AllAg.Caudate_Nucleus.bed ...

  4. File list: ALL.Neu.05.AllAg.Caudate_Nucleus [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Caudate_Nucleus hg19 All antigens Neural Caudate Nucleus SRX998283...,SRX998285 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.05.AllAg.Caudate_Nucleus.bed ...

  5. Cellular Neurophysiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Mechanisms of Synchronization

    Science.gov (United States)

    1994-07-29

    available concerning the important role of the suprachi- asmatic nucleus (SCN) in the generation of circadian rhythms (Klein et al., 1991), very little is...neurons are schematicized in terms of their numbers of asmatic nucleus; SDN, sexually dimorphic nucleus of the preoptic area; primary dendrites. ac

  6. Symmetry energy of the nucleus in the relativistic Thomas–Fermi ...

    Indian Academy of Sciences (India)

    The symmetry energy of a nucleus is determined in a local density approximation and integrating over the entire density distribution of the nucleus, calculated utilizing the relativistic density-dependent Thomas-Fermiapproach. The symmetry energy is found to decrease with increasing neutron excess in the nucleus.

  7. Gamma-ray spectroscopy of the nucleus {sup 139}Ce

    Energy Technology Data Exchange (ETDEWEB)

    Bucurescu, D.; Cata-Danil, G.; Cata-Danil, I.; Ivascu, M.; Marginean, N.; Marginean, R.; Mihailescu, L.C.; Rusu, C.; Suliman, G. [Horia Hulubei National Institute of Physics and Nuclear Engineering, P.O. Box MG-6, Bucharest (Romania)

    2006-03-15

    Gamma-ray coincidence techniques are used to determine new level structures in the N=81 nucleus {sup 139}Ce, at low spins and excitation energies with the {sup 139}La(p,n{gamma}) reaction at 5.0 and 6.0 MeV incident energy, and at high spins with the {sup 130}Te({sup 12}C,3n{gamma}) reaction at 50.5 MeV, respectively. Lifetime determinations are also made in the (p,n{gamma}) reaction with the centroid DSA method. The observed level structures are discussed by comparison with existing calculations and with those in the neighbouring nucleus {sup 140}Ce. (orig.)

  8. From Nucleons to Nucleus Concepts of Microscopic Nuclear Theory

    CERN Document Server

    Suhonen, Jouni

    2007-01-01

    From Nucleons to Nucleus deals with single-particle and collective features of spherical nuclei. Each nuclear model is introduced and derived in detail. The formalism is then applied to light and medium-heavy nuclei in worked-out examples, and finally the acquired skills are strengthened by a wide selection of exercises, many relating the models to experimental data. Nuclear properties are discussed using particles, holes and quasiparticles. A large number of matrix elements of standard operators have been tabulated for reference. From Nucleons to Nucleus is based on lectures on nuclear physics given by the author. Its main scope is thus to serve as a textbook for advanced students. But also researchers will appreciate it as wellbalanced reference to theoretical nuclear physics.

  9. Experiments on parity violation in the compound nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, J.D.

    1996-09-01

    Results from experiments that measure parity-violating longitudinal asymmetries in the scattering of epithermal neutrons from compound-nuclear resonances at the Manuel Lujan Neutron Scattering Center at Los Alamos are discussed. Parity non-conserving asymmetries have been observed for many p-wave resonances in a single target. Measurements were performed on several nuclei in the mass region of A-100 and A-230. The statistical model of the compound nucleus provides a theoretical basis for extracting mean-squared matrix elements from the experimental asymmetry data, and for interpreting the mean-squared matrix elements. The constraints on the weak meson-exchange couplings calculated from the compound-nucleus asymmetry data agree qualitatively with the results from few-body and light-nuclei experiments. For all nuclei but {sup 232}Th measured asymmetries have random signs. For {sup 232}Th eight of eight measured asymmetries are positive. This phenomenon is discussed in terms or doorway models.

  10. The abducens nucleus in the carpet shark Cephaloscyllium isabella.

    Science.gov (United States)

    Montgomery, J C; Housley, G D

    1983-12-01

    This study utilizes retrograde axonal transport of cobaltous-lysine, and conventional silver and Golgi staining techniques to study the abducens motor nucleus innervating the external rectus muscle of the carpet shark. The nucleus consists of 300-400 motoneurons located immediately ventrolateral to the medial longitudinal fasciculus (MLF), distributed over about 1.25 mm in a rostrocaudal direction at the level of exit of the VI nerve. The axons of the motoneurons form seven or eight discrete ventrally directed fascicles which, having exited from the brainstem, group together to form the abducens (VI) nerve. The motoneurons are on average about 16 micron in diameter, are bipolar, and their dendrites have a transverse orientation. Typically one set of dendrites penetrates the MLF and the other set extends ventrally into the reticular formation.

  11. The cellular mastermind(?) – Mechanotransduction and the nucleus

    Science.gov (United States)

    Kaminski, Ashley; Fedorchak, Gregory R.; Lammerding, Jan

    2015-01-01

    Cells respond to mechanical stimulation by activation of specific signaling pathways and genes that allow the cell to adapt to its dynamic physical environment. How cells sense the various mechanical inputs and translate them into biochemical signals remains an area of active investigation. Recent reports suggest that the cell nucleus may be directly implicated in this cellular mechanotransduction process. In this chapter, we discuss how forces applied to the cell surface and cytoplasm induce changes in nuclear structure and organization, which could directly affect gene expression, while also highlighting the complex interplay between nuclear structural proteins and transcriptional regulators that may further modulate mechanotransduction signaling. Taken together, these findings paint a picture of the nucleus as a central hub in cellular mechanotransduction—both structurally and biochemically—with important implications in physiology and disease. PMID:25081618

  12. Epilepsy, electroacupuncture and the nucleus of the solitary tract.

    Science.gov (United States)

    Cakmak, Yusuf Ozgur

    2006-12-01

    Vagal nerve stimulation and electroacupuncture have some promise as neuroprotective therapies for patients with poorly controlled epilepsy. It has been demonstrated that stimulation of acupuncture points on the extremities results in stimulation of the vagus nerve. It is possible that the antiepileptic effects of these two applications might be targeting the same centre in the brain. The nucleus of the solitary tract, which is a primary site at which vagal afferents terminate, is also the site for afferent pathways of facial, scalp and auricular acupuncture via trigeminal, cervical spinal and glossopharyngeal nerves. Taken together with laboratory findings, the neuroprotective pathways of electroacupuncture in epileptic models may stem from the collaboration of its anti-inflammatory and neurotrophic actions through the nucleus of the solitary tract via vagus nerve stimulation.

  13. Electromagnetic properties of the Beryllium-11 nucleus in Halo EFT

    Directory of Open Access Journals (Sweden)

    Hammer H.-W.

    2010-04-01

    Full Text Available We compute electromagnetic properties of the Beryllium-11 nucleus using an effective field theory that exploits the separation of scales in this halo system. We fix the parameters of the EFT from measured data on levels and scattering lengths in the 10Be plus neutron system. We then obtain predictions for the B(E1 strength of the 1/2+ to 1/2− transition in the 11Be nucleus. We also compute the charge radius of the ground state of 11Be. Agreement with experiment within the expected accuracy of a leading-order computation in this EFT is obtained. We also indicate how higher-order corrections that affect both s-wave and p-wave 10 Be-neutron interactions will affect our results.

  14. QCD evolution of the gluon density in a nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Ayala Filho, A.L. [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Inst. de Fisica]|[Universidade Federal de Pelotas, RS (Brazil). Inst. de Fisica e Matematica; Ducati, M.B. Gay [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Inst. de Fisica; Levin, E.M. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)]|[Petersburg Nuclear Physics Inst., St. Petersburg (Russian Federation). Theory Dept.

    1996-04-01

    The Glauber approach to the gluon density in a nucleus, suggested by A. Mueller, is developed and studied in detail. Using the GRV parameterization for the gluon density in a nucleon, the value as well as energy and Q{sup 2} dependence of the gluon density in a nucleus is calculated. It is shown that the shadowing corrections are under theoretical control and are essential in the region of small x. The change crucially the value of the gluon density as well as the value of the anomalous dimension of the nuclear structure function, unlike of the nucleon one. The systematic theoretical way to treat the correction to the Glauber approach is developed and a new evolution equation is derived and solved. It is shown that the solution of the new evolution equation can provide a self consistent matching of `soft` high energy phenomenology with `hard` QCD physics. (author). 51 refs., 25 figs., 1 tab.

  15. Hidden Glashow resonance in neutrino–nucleus collisions

    Directory of Open Access Journals (Sweden)

    I. Alikhanov

    2016-05-01

    Full Text Available Today it is widely believed that s-channel excitation of an on-shell W boson, commonly known as the Glashow resonance, can be initiated in matter only by the electron antineutrino in the process ν¯ee−→W− at the laboratory energy around 6.3 PeV. In this Letter we argue that the Glashow resonance within the Standard Model also occurs in neutrino–nucleus collisions. The main conclusions are as follows. 1 The Glashow resonance can be excited by both neutrinos and antineutrinos of all the three flavors scattering in the Coulomb field of a nucleus. 2 The Glashow resonance in a neutrino–nucleus reaction does not manifest itself as a Breit–Wigner-like peak in the cross section but the latter exhibits instead a slow logarithmic-law growth with the neutrino energy. The resonance turns thus out to be hidden. 3 More than 98% of W bosons produced in the sub-PeV region in neutrino-initiated reactions in water/ice will be from the Glashow resonance. 4 The vast majority of the Glashow resonance events in a neutrino detector are expected at energies from a few TeV to a few tens of TeV, being mostly initiated by the conventional atmospheric neutrinos dominant in this energy range. Calculations of the cross sections for Glashow resonance excitation on the oxygen nucleus as well as on the proton are carried out in detail. The results of this Letter can be useful for studies of neutrino interactions at large volume water/ice neutrino detectors. For example, in the IceCube detector one can expect 0.3 Glashow resonance events with shower-like topologies and the deposited energies above 300 TeV per year. It is therefore likely already to have at least one Glashow resonance event in the IceCube data set.

  16. mRNA-Producing Pseudo-nucleus System.

    Science.gov (United States)

    Shin, Seung Won; Park, Kyung Soo; Shin, Woo Jung; Um, Soong Ho

    2015-11-04

    A pseudo-eukaryotic nucleus (PEN) system consisting of a gene-containing DNA hydrogel encapsulated in a liposome is fabricated. Owing to the structural characteristics of gene-containing DNA hydrogel, mRNA transcription efficiency is promoted 2.57-fold. Through the use of PEN as a platform for mRNA delivery to the cytosol, prolonged protein translation is achieved. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Magnetic rotation in the nucleus 141Eu

    Energy Technology Data Exchange (ETDEWEB)

    Marcinkowska, Z.; Rzaca-Urban, T.; Droste, C.; Morek, T.; Czajkowska, B.; Urban, W.; Marcinkowski, R.; Olbratowski, P.; Lieder, R. M.; Brans, H.; Gast, W.; Jager, H. M.; Mihailescu, L.; Bazzacco, D.; Falconi, G.; Menegazzo, R.; Lunardi, S.; Rossi-Alvarez, C.; De Angelis, G.; Farnea, E.; Gadea, A.; Napoli, D. R.; Podolyak, Z.

    2003-04-01

    The previously known level scheme of 141 Eu nucleus was revised and substantially extended. Three dipole cascades, characterized by large B(M1)/B(E2) ratios, have been found. Spin and parity assignments were based on the angular distribution ratios and linear polarizations of γ-rays. The experimental results have been compared with the calculations of Tilted Axis Cranking (TAC) model.

  18. Depolarizing Actions of Hydrogen Sulfide on Hypothalamic Paraventricular Nucleus Neurons

    OpenAIRE

    C Sahara Khademullah; Ferguson, Alastair V.

    2013-01-01

    Hydrogen sulfide (H2S) is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH) secretion. Since the paraventricular nucleus of the hypothalamus (PVN) is a central relay center for autonomic and endocrine functions, we sought to investigate the effects of H2S on the neuronal population of the PVN. Whole cell current clamp recordings were acquired from the PVN neurons and sodium hydrosulfide hydrate (NaHS) was bath applied a...

  19. Isospin symmetry violation, meson production and η-nucleus ...

    Indian Academy of Sciences (India)

    nucleus interaction is the behaviour of N∗(1535) resonance in nuclear matter. Due to the large mass of η-meson (547 MeV), this S11 resonance is very close to η-N threshold. The resonance is also very broad with Γ ∼ 150 MeV covering the whole low energy region of η-nucleon interaction. The η-nucleon interaction at low ...

  20. Integration of sensory quanta in cuneate nucleus neurons in vivo.

    Directory of Open Access Journals (Sweden)

    Fredrik Bengtsson

    Full Text Available Discriminative touch relies on afferent information carried to the central nervous system by action potentials (spikes in ensembles of primary afferents bundled in peripheral nerves. These sensory quanta are first processed by the cuneate nucleus before the afferent information is transmitted to brain networks serving specific perceptual and sensorimotor functions. Here we report data on the integration of primary afferent synaptic inputs obtained with in vivo whole cell patch clamp recordings from the neurons of this nucleus. We find that the synaptic integration in individual cuneate neurons is dominated by 4-8 primary afferent inputs with large synaptic weights. In a simulation we show that the arrangement with a low number of primary afferent inputs can maximize transfer over the cuneate nucleus of information encoded in the spatiotemporal patterns of spikes generated when a human fingertip contact objects. Hence, the observed distributions of synaptic weights support high fidelity transfer of signals from ensembles of tactile afferents. Various anatomical estimates suggest that a cuneate neuron may receive hundreds of primary afferents rather than 4-8. Therefore, we discuss the possibility that adaptation of synaptic weight distribution, possibly involving silent synapses, may function to maximize information transfer in somatosensory pathways.

  1. The Nuclear Option: Evidence Implicating the Cell Nucleus in Mechanotransduction.

    Science.gov (United States)

    Szczesny, Spencer E; Mauck, Robert L

    2017-02-01

    Biophysical stimuli presented to cells via microenvironmental properties (e.g., alignment and stiffness) or external forces have a significant impact on cell function and behavior. Recently, the cell nucleus has been identified as a mechanosensitive organelle that contributes to the perception and response to mechanical stimuli. However, the specific mechanotransduction mechanisms that mediate these effects have not been clearly established. Here, we offer a comprehensive review of the evidence supporting (and refuting) three hypothetical nuclear mechanotransduction mechanisms: physical reorganization of chromatin, signaling at the nuclear envelope, and altered cytoskeletal structure/tension due to nuclear remodeling. Our goal is to provide a reference detailing the progress that has been made and the areas that still require investigation regarding the role of nuclear mechanotransduction in cell biology. Additionally, we will briefly discuss the role that mathematical models of cell mechanics can play in testing these hypotheses and in elucidating how biophysical stimulation of the nucleus drives changes in cell behavior. While force-induced alterations in signaling pathways involving lamina-associated polypeptides (LAPs) (e.g., emerin and histone deacetylase 3 (HDAC3)) and transcription factors (TFs) located at the nuclear envelope currently appear to be the most clearly supported mechanism of nuclear mechanotransduction, additional work is required to examine this process in detail and to more fully test alternative mechanisms. The combination of sophisticated experimental techniques and advanced mathematical models is necessary to enhance our understanding of the role of the nucleus in the mechanotransduction processes driving numerous critical cell functions.

  2. Ground control to major TOM: mitochondria-nucleus communication.

    Science.gov (United States)

    Eisenberg-Bord, Michal; Schuldiner, Maya

    2017-01-01

    Mitochondria have crucial functions in the cell, including ATP generation, iron-sulfur cluster biogenesis, nucleotide biosynthesis, and amino acid metabolism. All of these functions require tight regulation on mitochondrial activity and homeostasis. As mitochondria biogenesis is controlled by the nucleus and almost all mitochondrial proteins are encoded by nuclear genes, a tight communication network between mitochondria and the nucleus has evolved, which includes signaling cascades, proteins which are dual-localized to the two compartments, and sensing of mitochondrial products by nuclear proteins. All of these enable a crosstalk between mitochondria and the nucleus that allows the 'ground control' to get information on mitochondria's status. Such information facilitates the creation of a cellular balance of mitochondrial status with energetic needs. This communication also allows a transcriptional response in case mitochondrial function is impaired aimed to restore mitochondrial homeostasis. As mitochondrial dysfunction is related to a growing number of genetic diseases as well as neurodegenerative conditions and aging, elucidating the mechanisms governing the mitochondrial/nuclear communication should progress a better understanding of mitochondrial dysfunctions. © 2016 Federation of European Biochemical Societies.

  3. Incorporation of mammalian actin into microfilaments in plant cell nucleus

    Directory of Open Access Journals (Sweden)

    Paves Heiti

    2004-04-01

    Full Text Available Abstract Background Actin is an ancient molecule that shows more than 90% amino acid homology between mammalian and plant actins. The regions of the actin molecule that are involved in F-actin assembly are largely conserved, and it is likely that mammalian actin is able to incorporate into microfilaments in plant cells but there is no experimental evidence until now. Results Visualization of microfilaments in onion bulb scale epidermis cells by different techniques revealed that rhodamine-phalloidin stained F-actin besides cytoplasm also in the nuclei whereas GFP-mouse talin hybrid protein did not enter the nuclei. Microinjection of fluorescently labeled actin was applied to study the presence of nuclear microfilaments in plant cells. Ratio imaging of injected fluorescent rabbit skeletal muscle actin and phalloidin staining of the microinjected cells showed that mammalian actin was able to incorporate into plant F-actin. The incorporation occurred preferentially in the nucleus and in the perinuclear region of plant cells whereas part of plant microfilaments, mostly in the periphery of cytoplasm, did not incorporate mammalian actin. Conclusions Microinjected mammalian actin is able to enter plant cell's nucleus, whereas incorporation of mammalian actin into plant F-actin occurs preferentially in the nucleus and perinuclear area.

  4. The granulocyte nucleus and lamin B receptor: avoiding the ovoid.

    Science.gov (United States)

    Hoffmann, Katrin; Sperling, Karl; Olins, Ada L; Olins, Donald E

    2007-06-01

    The major human blood granulocyte, the neutrophil, is an essential component of the innate immunity system, emigrating from blood vessels and migrating through tight tissue spaces to the site of bacterial or fungal infection where they kill and phagocytose invading microbes. Since the late nineteenth century, it has been recognized that the human neutrophil nucleus is distinctly not ovoid as in other cell types, but possesses a lobulated (segmented) shape. This deformable nucleus enhances rapid migration. Recent studies have demonstrated that lamin B receptor (LBR) is necessary for the non-ovoid shape. LBR is an integral membrane protein of the nuclear envelope. A single dominant mutation in humans leads to neutrophils with hypolobulated nuclei (Pelger-Huet anomaly); homozygosity leads to ovoid granulocyte nuclei. Interestingly, LBR is also an enzyme involved in cholesterol metabolism. Homozygosity for null mutations is frequently lethal and associated with severe skeletal deformities. In addition to the necessity for LBR, formation of the mature granulocyte nucleus also depends upon lamin composition and microtubule integrity. These observations are part of a larger question on the relationships between nuclear shape and cellular function.

  5. Experimental studies of pion-nucleus interactions at intermediate energies

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-31

    This report summarizes the work on experimental research in intermediate energy nuclear physics carried out at New Mexico State University in 1991 under a great from the US Department of Energy. Most of these studies have involved investigations of various pion-nucleus interactions. The work has been carried out both with the LAMPF accelerator at the Los Alamos National Laboratory and with the cyclotron at the Paul Scherrer Institute (PSI) near Zurich, Switzerland. Part of the experimental work involves measurements of new data on double-charge-exchange scattering, using facilities at LAMPF which we helped modify, and on pion absorption, using a new detector system at PSI that covers nearly the full solid-angle region which we helped construct. Other work involved preparation for future experiments using polarized nuclear targets and a new high-resolution spectrometer system for detecting {pi}{sup 0} mesons. We also presented several proposals for works to be done in future years, involving studies related to pi-mesonic atoms, fundamental pion-nucleon interactions, studies of the difference between charged and neutral pion interactions with the nucleon, studies of the isospin structure of pion-nucleus interactions, and pion scattering from polarized {sup 3}He targets. This work is aimed at improving our understanding of the pion-nucleon interaction, of the pion-nucleus interaction mechanism, and of nuclear structure.

  6. Projections from the subdivisions of the fastigial nucleus to the vestibular complex and the prepositus hypoglossal nucleus in the albino rat: an anterograde tracing study using biocytin.

    Science.gov (United States)

    Omori, O; Umetani, T; Sugioka, K

    1997-02-01

    Differential projections from the subdivisions of the fastigial nucleus to the vestibular complex and the prepositus hypoglossal nucleus were investigated by an anterograde tracing method using biocytin in the albino rat. The caudomedial subdivision of the nucleus projected ipsilaterally to the dorsal and medial parts of the superior vestibular nucleus (Su Ve), the dorsomedial part of the lateral vestibular nucleus (LVe), and the dorsal parts of the medial (MVe) and spinal (Sp Ve) vestibular nuclei, and projected contralaterally to the ventrolateral corners of the Su Ve and LVe, the ventral part of the MVe, and the lateral part of the Sp Ve. The bilateral prepositus hypoglossal nuclei received sparse projections from the caudomedial subdivision. The middle subdivision of the fastigial nucleus projected ipsilaterally to the dorsal and/or ventral parts of the Su Ve, the dorsomedial pats of the LVe and Sp Ve, and the dorsolateral part of the MVe, and projected contralaterally to the dorsal margin of the Su Ve, the ventrolateral part of the LVe, and the lateral part of the Sp Ve. The dorsolateral protuberance of the fastigial nucleus projected ipsilaterally to the dorsal margin of the Su Ve, the dorsomedial part of the LVe, the dorsal or lateral parts of the Sp Ve, and the lateral part of the MVe, and projected contralaterally to the ventrolateral part of the LVe and the lateral part of the Sp Ve. The subnuclei x, y, and f, interstitial nucleus of the vestibular nerve, and the infracerebellar nucleus received bilateral or ipsilateral fastigiovestibular projections.

  7. A transport set-up for heavy-flavour observables in nucleus-nucleus collisions at RHIC and LHC

    CERN Document Server

    Nardi, Marzia; Beraudo, A; De Pace, A; Molinari, A; Monteno, M; Prino, F; Sitta, M

    2014-01-01

    A multi-step setup for heavy-flavour studies in high-energy nucleus–nucleus collisions is presented. The initial hard production of View the MathML sourceQ$\\bar{Q}$ pairs is simulated with the POWHEG pQCD event generator, interfaced with the PYTHIA parton shower. In a nucleus–nucleus collision the propagation of the heavy quarks in the medium is described through the relativistic Langevin equation. The numerical results are compared to experimental data from the RHIC and the LHC. In particular we show the comparisons of the nuclear modification factor of D-mesons, non-prompt J/ψJ/ψ's and heavy-flavour electrons. Furthermore, first results on azimuthal correlations of heavy quark pair and open charm/beauty meson pairs are presented.

  8. Dielectron Cross Section Measurements in Nucleus-Nucleus Reactions at 1.0{ital A} GeV

    Energy Technology Data Exchange (ETDEWEB)

    Porter, R.J.; Bossingham, R.; Gong, W.G.; Heilbronn, L.; Huang, H.Z.; Krebs, G.; Letessier-Selvon, A.; Matis, H.S.; Miller, J.; Naudet, C.; Roche, G.; Schroeder, L.S.; Seidl, P.; Wilson, W.K.; Yegneswaran, A. [Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720 (United States); Beedoe, S.; Carroll, J.; Huang, H.Z.; Igo, G. [University of California at Los Angeles, California 90095 (United States); Bougteb, M.; Manso, F.; Prunet, M.; Roche, G. [Universite Blaise Pascal/IN2P3, 63177 Aubiere Cedex (France); Christie, W.B.; Hallman, T.; Madansky, L.; Welsh, R.C. [The Johns Hopkins University, Baltimore, Maryland 21218 (United States); Kirk, P.; Wang, Z.F. [Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Wilson, W.K. [Wayne State University, Detroit, Michigan 48201 (United States)

    1997-08-01

    We present measured dielectron production cross sections for Ca+Ca, C+C, He+Ca, and d+Ca reactions at 1.0 A GeV . Statistical uncertainties and systematic effects are smaller than in previous dilepton spectrometer (DLS) nucleus-nucleus data. For pair mass M{le}0.35 GeV/c{sup 2} we obtain (1) the Ca+Ca cross section is larger than the previous DLS measurement and current model results, (2) the mass spectra suggest large contributions from {pi}{sup 0} and {eta} Dalitz decays, and (3) d{sigma}/dM{proportional_to}A{sub P}A{sub T}. For M{gt}0.5 GeV/c{sup 2} the Ca+Ca to C+C cross section ratio is significantly larger than the ratio of A{sub P}A{sub T} values. {copyright} {ital 1997} {ital The American Physical Society}

  9. Long noncoding RNAs coordinate functions between mitochondria and the nucleus.

    Science.gov (United States)

    Dong, Yaru; Yoshitomi, Takeshi; Hu, Ji-Fan; Cui, Jizhe

    2017-08-23

    In animal cells, mitochondria are the primary powerhouses and metabolic factories. They also contain genomes and can produce mitochondrial-specific nucleic acids and proteins. To maintain homeostasis of the entire cell, an intense cross-talk between mitochondria and the nucleus, mediated by encoded noncoding RNAs (ncRNAs), as well as proteins, is required. Long ncRNAs (lncRNAs) contain characteristic structures, and they are involved in the regulation of almost every stage of gene expression, as well as being implicated in a variety of disease states, such as cancer. In the coordinated signaling system, several lncRNAs, transcribed in the nucleus but residing in mitochondria, play a key role in regulating mitochondrial functions or dynamics. For example, RMRP, a component of the mitochondrial RNase MRP, is important for mitochondrial DNA replication and RNA processing, and the steroid receptor RNA activator, SRA, is a key modulator of hormone signaling and is present in both the nucleus and mitochondria. Some RNA-binding proteins maybe play a role in the lncRNAs transport system, such as HuR, GRSF1, SHARP, SLIRP, PPR, and PNPASE. Furthermore, a series of nuclear DNA-encoded lncRNAs were implicated in mitochondria-mediated apoptosis, mitochondrial bioenergetics and biosynthesis, and glutamine metabolism. The mitochondrial genome can also encode a set of lncRNAs, and they are divided into three categories: (1) lncND5, lncND6, and lncCyt b RNA; (2) chimeric mitochondrial DNA-encoded lncRNAs; and (3) putative mitochondrial DNA-encoded lncRNAs. It has been reported that the mitochondrial DNA-encoded lncRNAs appear to operate in the nucleus. The molecular mechanisms underlying trafficking of the mitochondrial DNA-encoded lncRNAs to the nucleus in mammals are only now beginning to emerge. In conclusion, both nuclear- and mitochondrial DNA-encoded lncRNAs mediate an intense intercompartmental cross-talk, which opens a rich field for investigation of the mechanism

  10. Nucleus-encoded periplastid-targeted EFL in chlorarachniophytes.

    Science.gov (United States)

    Gile, Gillian H; Keeling, Patrick J

    2008-09-01

    Chlorarachniophytes are cercozoan amoeboflagellates that acquired photosynthesis by enslaving a green alga, which has retained a highly reduced nucleus called a nucleomorph. The nucleomorph lacks many genes necessary for its own maintenance and expression, suggesting that some genes have been moved to the host nucleus and their products are now targeted back to the periplastid compartment (PPC), the reduced eukaryotic cytoplasm of the endosymbiont. Protein trafficking in chlorarachniophytes is therefore complex, including nucleus-encoded plastid-targeted proteins, nucleomorph-encoded plastid-targeted proteins, and nucleus-encoded periplastid-targeted proteins. A major gap in our understanding of this system is the PPC-targeted proteins because none have been described in any chlorarachniophytes. Here we describe the first such protein, the GTPase EFL. EFL was characterized from 7 chlorarachniophytes, and 2 distinct types were found. One is related to foraminiferan EFL and lacks an amino-terminal extension. The second, distantly related, type encodes an amino-terminal extension consisting of a signal peptide followed by sequence sharing many characteristics with transit peptides from nucleus-encoded plastid-targeted proteins and which we conclude is most likely PPC targeted. Western blotting with antibodies specific to putative host and PPC-targeted EFL from the chlorarachniophytes Bigelowiella natans and Gymnochlora stellata is consistent with posttranslational cleavage of the leaders from PPC-targeted proteins. Immunolocalization of both proteins in B. natans confirmed the cytosolic location of the leaderless EFL and a distinct localization pattern for the PPC-targeted protein but could not rule out a plastid location (albeit very unlikely). We sought other proteins with a similar leader and identified a eukaryotic translation initiation factor 1 encoding a bipartite extension with the same properties. Transit peptide sequences were characterized from all 3

  11. Hearing preservation outcomes with different cochlear implant electrodes: Nucleus® Hybrid™-L24 and Nucleus Freedom™ CI422.

    Science.gov (United States)

    Jurawitz, Marie-Charlot; Büchner, Andreas; Harpel, Theo; Schüssler, Mark; Majdani, Omid; Lesinski-Schiedat, Anke; Lenarz, Thomas

    2014-01-01

    In recent years, it has been possible to preserve hearing after cochlear implantation in patients with significant amounts of low-frequency residual hearing. Due to the dimensions and characteristics of the cochlear implants (CIs) Nucleus® Hybrid™-L24 and Nucleus Freedom™ CI422, both can be used to preserve residual hearing. The aim was to investigate the degree and progression of hearing preservation over a longitudinal postoperative period in a large consecutive cohort of implanted patients with preoperative residual hearing who received either the Nucleus Hybrid-L24 or the Nucleus Freedom CI422 implant. The intention was to examine potential characteristics and triggers of resulting postoperative hearing loss which may support a differentiation of CI candidacy criteria for a certain implant type. A retrospective data analysis of patient files on consecutively implanted subjects presenting with a severe-to-profound sensorineural hearing loss at frequencies>1,500 Hz and substantial residual hearing at frequencies≤1,500 Hz, implanted with a Nucleus Hybrid-L24 (n=97) or a CI422 implant (n=100), was undertaken. A single-subject repeated-measure design comparing the mean threshold shift for pure-tone thresholds under headphones up to 24 months after implantation was used. Hearing preservation is observed in the majority of subjects with either implant (250-1,500 Hz frequency range). Hybrid-L24 patients exhibited a median hearing loss of 10 dB at initial fitting (n=97) and of 15 dB after 24 months (n=51). A 14.4-dB decrease in median hearing loss at initial fitting (n=100) and a 30-dB decrease after 24 months (n=28) was observed with the CI422 electrode. At initial fitting, 54.6% of the Hybrid-L24 (n=97) and 49.0% of the CI422 (n=100) subjects showed a mean threshold shifthearing was preserved for the majority of implanted patients with the Hybrid-L24 and the CI422 implant. Patients implanted with the Hybrid-L24 implant demonstrate greater stability and less

  12. Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats.

    Science.gov (United States)

    Wang, Junshi; Bina, Robert W; Wingard, Jeffrey C; Terwilliger, Ernest F; Hammer, Ronald P; Nikulina, Ella M

    2014-03-01

    The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas AAV-GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10 days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross-sensitization to amphetamine compared with the handled rats. In contrast, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-extracellular signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as ΔFosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc ΔFosB accumulation that could trigger cross-sensitization after social defeat stress. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Neurochemical organization of the nucleus paramedianus dorsalis in the human.

    Science.gov (United States)

    Baizer, Joan S; Baker, James F; Haas, Kristin; Lima, Raquel

    2007-10-24

    We have characterized the neurochemical organization of a small brainstem nucleus in the human brain, the nucleus paramedianus dorsalis (PMD). PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (antibody SMI-32). In transverse sections, PMD is oval with its long axis aligned with the dorsal border of the brainstem. We identified PMD in eight human brainstems, but found some variability both in its cross-sectional area and in its A-P extent among cases. It includes calretinin immunoreactive large cells with oval or polygonal cell bodies. Cells in PMD are not immunoreactive for either calbindin or parvalbumin, but a few fibers immunoreactive to each protein are found within its central region. Cells in PMD are also immunoreactive to nNOS, and immunoreactivity to a neurofilament protein shows many labeled cells and fibers. No similar region is identified in atlases of the cat, mouse, rat or monkey brain, nor does immunoreactivity to any of the markers that delineate it in the human reveal a comparable region in those species. The territory that PMD occupies is included in PH in other species. Since anatomical and physiological data in animals suggest that PH may have multiple subregions, we suggest that the PMD in human may be a further differentiation of PH and may have functions related to the vestibular control of eye movements.

  14. Separable representation of multichannel nucleon-nucleus optical potentials

    Science.gov (United States)

    Hlophe, L.; Elster, Ch.

    2017-05-01

    Background: One important ingredient for many applications of nuclear physics to astrophysics, nuclear energy, and stockpile stewardship is cross sections for reactions of neutrons with rare isotopes. Since direct measurements are often not feasible, indirect methods, e.g., (d ,p ) reactions, should be used. Those (d ,p ) reactions may be viewed as three-body reactions and described with Faddeev techniques. Purpose: Faddeev equations in momentum space have a long tradition of utilizing separable interactions in order to arrive at sets of coupled integral equations in one variable. Optical potentials representing the effective interactions in the neutron (proton) nucleus subsystem are usually non-Hermitian as well as energy dependent. Including excitations of the nucleus in the calculation requires a multichannel optical potential. The purpose of this paper is to introduce a separable, energy-dependent multichannel representation of complex, energy-dependent optical potentials that contain excitations of the nucleus and that fulfill reciprocity exactly. Methods: Momentum space Lippmann-Schwinger integral equations are solved with standard techniques to obtain the form factors for the separable representation. Results: Starting from energy-dependent multichannel optical potentials for neutron and proton scattering from 12C, separable representations based on a generalization of the Ernst-Shakin-Thaler (EST) scheme are constructed which fulfill reciprocity exactly. Applications to n +12C and p +12C scattering are investigated for energies from 0 to 50 MeV. Conclusions: We find that the energy-dependent separable representation of complex, energy-dependent phenomenological multichannel optical potentials describes scattering data with the same quality as the original potential.

  15. Neutrino–nucleus cross sections for oscillation experiments

    Science.gov (United States)

    Katori, Teppei; Martini, Marco

    2018-01-01

    Neutrino oscillations physics is entering an era of high precision. In this context, accelerator-based neutrino experiments need a reduction in systematic errors to the level of a few percent. Today, one of the most important sources of systematic errors are neutrino–nucleus cross sections which, in the energy region of hundreds of MeV to a few GeV, are known to a precision not exceeding 20%. In this article we review the present experimental and theoretical knowledge of neutrino–nucleus interaction physics. After introducing neutrino-oscillation physics and accelerator-based neutrino experiments, we give an overview of general aspects of neutrino–nucleus cross sections, from both the theoretical and experimental point of view. Then, we focus on these cross sections in different reaction channels. We start with the quasi-elastic and quasi-elastic-like cross section, placing a special emphasis on the multinucleon emission channel, which has attracted a lot of attention in the last few years. We review the main aspects of the different microscopic models for this channel by discussing analogies and the differences among them. The discussion is always driven by a comparison with the experimental data. We then consider the one-pion production channel where agreement between data and theory remains highly unsatisfactory. We describe how to interpret pion data, and then analyze, in particular, the puzzle related to the difficulty of theoretical models and Monte Carlo to simultaneously describe MiniBooNE and MINERvA experimental results. Inclusive cross sections are also discussed, as well as the comparison between the {ν }μ and {ν }e cross sections, relevant for the charge-conjugation-parity violation experiments. The impact of nuclear effects on the reconstruction of neutrino energy and on the determination of the neutrino-oscillation parameters is also reviewed. Finally, we look to the future by discussing projects and efforts in relation to future detectors

  16. Identification of penile inputs to the rat gracile nucleus.

    Science.gov (United States)

    Cothron, Kyle J; Massey, James M; Onifer, Stephen M; Hubscher, Charles H

    2008-03-01

    Neurons in the medullary reticular formation (MRF) of the rat receive a vast array of urogenital inputs. Using select acute and chronic spinal cord lesions to identify the location of the ascending neural circuitries providing either direct or indirect inputs to MRF from the penis, our previous studies demonstrated that the dorsal columns and dorsal half of the lateral funiculus convey low- and high-threshold inputs, respectively. In the present study, the gracile nucleus was targeted as one of the likely sources of low-threshold information from the penis to MRF. Both electrophysiological recordings and neuroanatomical tracing [injection of cholera toxin B subunit (CTB) into a dorsal nerve of the penis] were used. After discrimination of a single neuron responding to penile stimulation, testing for somatovisceral convergence was done (mechanical stimulation of the distal colon and the skin over the entire hindquarters). In 12 rats, a limited number of neurons (43 in total) responded to penile stimulation. Many of these neurons also responded to scrotal stimulation (53.5%, dorsal and/or ventral scrotum) and/or prepuce stimulation (46.5%). Histological reconstruction of the electrode tracks showed that the majority of neurons responding to penile stimulation were located ventrally within the medial one-third of the gracile nucleus surrounding obex. This location corresponded to sparse innervation by CTB-immunoreactive primary afferent terminals. These results indicate that neurons in the gracile nucleus are likely part of the pathway that provides low-threshold penile inputs to MRF, a region known to play an important role in mating processes.

  17. Cloud condensation nucleus behaviour of selected dicarboxylic acids

    DEFF Research Database (Denmark)

    Poulsen, Mia Frosch Mogensbæk; Nielsen, Ole Faurskov; Bilde, Merete

    Due to relatively high water solubilities and low volatilities under ambient conditions, dicarboxylic acids have a high potential for forming aerosols, i.e. act as cloud condensation nuclei (CCN). Futhermore, dicarboxylic acids have been detected in atmospheric aerosols on many different sites (e.......g. Anttila et al, 2005). Particles composed of two such compounds, namely glutaric acid and pimelic acid, have been studied using a cloud condensation nucleus counter (University of Wyoming, Model 100B). The behaviour of pimelic acid seems to agree quite well with the predictions of Köhler theory. This...

  18. First allowed bandcrossing in neutron deficient nucleus {sup 141}Tb

    Energy Technology Data Exchange (ETDEWEB)

    Medina, N.H.; Oliveira, J.R.B.; Cybulska, E.W.; Rao, M.N.; Ribas, R.V.; Rizzutto, M.A.; Seale, W.A. [Sao Paulo Univ., SP (Brazil). Inst. de Fisica; Espinoza-Quinones, F.R. [Universidade Estadual do Oeste do Parana, Toledo, PR (Brazil). Centro de Engenharia e Ciencias Exatas; Bazzacco, D.; Brandolini, F.; Lunardi, S.; Petrache, C.M.; Podolyak, Zs.; Rossi-Alvarez, C.; Soramel, F.; Ur, C.A. [Istituto Nazionale di Fisica Nucleare, Padova (Italy); Cardona, M.A.; Angelis, G. de; Napoli, D.R.; Spolaore, P.; Gadea, A.; Acua, D. de; Poli, M. de; Farnea, E.; Foltescu, D.; Ionescu-Bujor, M.; Iordachescu, A. [Istituto Nazionale di Fisica Nucleare, Legnaro (Italy). Laboratori Nazionali

    2004-09-15

    The neutron deficient {sup 141}Tb nucleus has been studied with the {sup 92}Mo ({sup 54}Fe, {alpha}-) reaction at 240-MeV incident energy and the multidetector array GASP. For the yrast {pi}h{sub 11/2} decoupled band, excited states up to 6.7 MeV and spin up to 47=2{sup -} have been observed. This band presents an upbend at rotational frequency of Plank constant{omega}=0:38 MeV due to the alignment of h{sub 11}/{sub 2} protons. The results are discussed in terms of the Cranking model. (author)

  19. Neutrino-nucleus interactions and the determination of oscillation parameters

    Science.gov (United States)

    Benhar, Omar; Huber, Patrick; Mariani, Camillo; Meloni, Davide

    2017-07-01

    We review the status and prospects of theoretical studies of neutrino-nucleus interactions, and discuss the influence of the treatment of nuclear effects on the determination of oscillation parameters. The models developed to describe the variety of reaction mechanisms contributing to the nuclear cross sections are analyzed, with emphasis placed on their capability to explain the large body of available electron scattering data. The impact of the uncertainties associated with the description of nuclear structure and dynamics on the determination of oscillation parameters is illustrated through examples, and possible avenues towards a better understanding of the signals detected by accelerator-based experiments are outlined.

  20. Red nucleus and rubrospinal tract disorganization in the absence of Pou4f1

    Directory of Open Access Journals (Sweden)

    Jesus E. eMartinez-Lopez

    2015-02-01

    Full Text Available The red nucleus is a neuronal population that plays an important role in forelimb motor control and locomotion. Histologically it is subdivided into two subpopulations, the parvocellular red nucleus located in the diencephalon and the magnocellular red nucleus in the mesencephalon. The red nucleus integrates signals from motor cortex and cerebellum and projects to spinal cord interneurons and motor neurons through the rubrospinal tract. Pou4f1 is a transcription factor highly expressed in this nucleus that has been related to its specification. Here we profoundly analyzed consequences of Pou4f1 loss-of-function in development, maturation and axonal projection of the red nucleus. Surprisingly, red nucleus neurons are specified and maintained in the mutant, no cell death was detected. Nevertheless, the nucleus appeared disorganized with a strong delay in radial migration and with a wider neuronal distribution; the neurons did not form a compacted population as they do in controls, Robo1 and Slit2 were miss-expressed. Cplx1 and Npas1, expressed in the red nucleus, are transcription factors involved in neurotransmitter release, neuronal maturation and motor function processes among others. In our mutant mice, both transcription factors are lost, suggesting an abnormal maturation of the red nucleus. The resulting altered nucleus occupied a wider territory. Finally, we examined rubrospinal tract development and found that the red nucleus neurons were able to project to the spinal cord but their axons appeared defasciculated. These data suggest that Pou4f1 is necessary for the maturation of red nucleus neurons but not for their specification and maintenance.

  1. Finding Hierarchical and Overlapping Dense Subgraphs using Nucleus Decompositions

    Energy Technology Data Exchange (ETDEWEB)

    Seshadhri, Comandur [The Ohio State Univ., Columbus, OH (United States); Pinar, Ali [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sariyuce, Ahmet Erdem [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Catalyurek, Umit [The Ohio State Univ., Columbus, OH (United States)

    2014-11-01

    Finding dense substructures in a graph is a fundamental graph mining operation, with applications in bioinformatics, social networks, and visualization to name a few. Yet most standard formulations of this problem (like clique, quasiclique, k-densest subgraph) are NP-hard. Furthermore, the goal is rarely to nd the \\true optimum", but to identify many (if not all) dense substructures, understand their distribution in the graph, and ideally determine a hierarchical structure among them. Current dense subgraph nding algorithms usually optimize some objective, and only nd a few such subgraphs without providing any hierarchy. It is also not clear how to account for overlaps in dense substructures. We de ne the nucleus decomposition of a graph, which represents the graph as a forest of nuclei. Each nucleus is a subgraph where smaller cliques are present in many larger cliques. The forest of nuclei is a hierarchy by containment, where the edge density increases as we proceed towards leaf nuclei. Sibling nuclei can have limited intersections, which allows for discovery of overlapping dense subgraphs. With the right parameters, the nuclear decomposition generalizes the classic notions of k-cores and k-trusses. We give provable e cient algorithms for nuclear decompositions, and empirically evaluate their behavior in a variety of real graphs. The tree of nuclei consistently gives a global, hierarchical snapshot of dense substructures, and outputs dense subgraphs of higher quality than other state-of-theart solutions. Our algorithm can process graphs with tens of millions of edges in less than an hour.

  2. Neutrino-nucleus reactions based on recent structure studies

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Toshio [Department of Physics and Graduate School of Integrated Basic Sciences, College of Humanities and Sciences, Nihon University, Sakurajosui 3-25-40, Setagaya-ku, Tokyo 156-8550 (Japan); National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan)

    2015-05-15

    Neutrino-nucleus reactions are studied with the use of new shell model Hamiltonians, which have proper tensor components in the interactions and prove to be successful in the description of Gamow-Teller (GT) strengths in nuclei. The new Hamiltonians are applied to obtain new neutrino-nucleus reaction cross sections in {sup 12}C, {sup 13}C, {sup 56}Fe and {sup 56}Ni induced by solar and supernova neutrinos. The element synthesis by neutrino processes in supernova explosions is discussed with the new cross sections. The enhancement of the production yields of {sup 7}Li, {sup 11}B and {sup 55}Mn is obtained while fragmented GT strength in {sup 56}Ni with two-peak structure is found to result in smaller e-capture rates at stellar environments. The monopole-based universal interaction with tensor force of π+ρ meson exchanges is used to evaluate GT strength in {sup 40}Ar and ν-induced reactions on {sup 40}Ar. It is found to reproduce well the experimental GT strength in {sup 40}Ar.

  3. Axonal branching patterns of nucleus accumbens neurons in the rat.

    Science.gov (United States)

    Tripathi, Anushree; Prensa, Lucía; Cebrián, Carolina; Mengual, Elisa

    2010-11-15

    The patterns of axonal collateralization of nucleus accumbens (Acb) projection neurons were investigated in the rat by means of single-axon tracing techniques using the anterograde tracer biotinylated dextran amine. Seventy-three axons were fully traced, originating from either the core (AcbC) or shell (AcbSh) compartment, as assessed by differential calbindin D28k-immunoreactivity. Axons from AcbC and AcbSh showed a substantial segregation in their targets; target areas were either exclusively or preferentially innervated from AcbC or AcbSh. Axon collaterals in the subthalamic nucleus were found at higher than expected frequencies; moreover, these originated exclusively in the dorsal AcbC. Intercompartmental collaterals were observed from ventral AcbC axons into AcbSh, and likewise, interconnections at pallidal and mesencephalic levels were also observed, although mostly from AcbC axons toward AcbSh targets, possibly supporting crosstalk between the two subcircuits at several levels. Cell somata giving rise to short-range accumbal axons, projecting to the ventral pallidum (VP), were spatially intermingled with others, giving rise to long-range axons that innervated VP and more caudal targets. This anatomical organization parallels that of the dorsal striatum and provides the basis for possible dual direct and indirect actions from a single axon on either individual or small sets of neurons. Copyright © 2010 Wiley-Liss, Inc.

  4. Commissural neurons in the rat ventral cochlear nucleus.

    Science.gov (United States)

    Doucet, John R; Lenihan, Nicole M; May, Bradford J

    2009-06-01

    Commissural neurons connect the cochlear nucleus complexes of both ears. Previous studies have suggested that the neurons may be separated into two anatomical subtypes on the basis of percent apposition (PA); that is, the percentage of the soma apposed by synaptic terminals. The present study combined tract tracing with synaptic immunolabeling to compare the soma area, relative number, and location of Type I (low PA) and Type II (high PA) commissural neurons in the ventral cochlear nucleus (VCN) of rats. Confocal microscopic analysis revealed that 261 of 377 (69%) commissural neurons have medium-sized somata with Type I axosomatic innervation. The commissural neurons also showed distinct topographical distributions. The majority of Type I neurons were located in the small cell cap of the VCN, which serves as a nexus for regulatory pathways within the auditory brainstem. Most Type II neurons were found in the magnocellular core. This anatomical dichotomy should broaden current views on the function of the commissural pathway that stress the fast inhibitory interactions generated by Type II neurons. The more prevalent Type I neurons may underlie slow regulatory influences that enhance binaural processing or the recovery of function after injury.

  5. Monte Carlo Simulation for Statistical Decay of Compound Nucleus

    Directory of Open Access Journals (Sweden)

    Chadwick M.B.

    2012-02-01

    Full Text Available We perform Monte Carlo simulations for neutron and γ-ray emissions from a compound nucleus based on the Hauser-Feshbach statistical theory. This Monte Carlo Hauser-Feshbach (MCHF method calculation, which gives us correlated information between emitted particles and γ-rays. It will be a powerful tool in many applications, as nuclear reactions can be probed in a more microscopic way. We have been developing the MCHF code, CGM, which solves the Hauser-Feshbach theory with the Monte Carlo method. The code includes all the standard models that used in a standard Hauser-Feshbach code, namely the particle transmission generator, the level density module, interface to the discrete level database, and so on. CGM can emit multiple neutrons, as long as the excitation energy of the compound nucleus is larger than the neutron separation energy. The γ-ray competition is always included at each compound decay stage, and the angular momentum and parity are conserved. Some calculations for a fission fragment 140Xe are shown as examples of the MCHF method, and the correlation between the neutron and γ-ray is discussed.

  6. Gas inflows towards the nucleus of NGC 1358

    Science.gov (United States)

    Schnorr-Müller, Allan; Storchi-Bergmann, Thaisa; Nagar, Neil M.; Robinson, Andrew; Lena, Davide

    2017-11-01

    We use optical spectra from the inner 1.8 × 2.5 kpc2 of the Seyfert 2 galaxy NGC 1358, obtained with the GMOS integral field spectrograph on the Gemini South telescope at a spatial resolution of ≈ 165 pc, to assess the feeding and feedback processes in this nearby active galaxy. Five gaseous kinematical components are observed in the emission line profiles. One of the components is present in the entire field-of-view and we interpret it as due to gas rotating in the disc of the galaxy. Three of the remaining components we interpret as associated with active galactic nucleus (AGN) feedback: a compact unresolved outflow in the inner 1 arcsec and two gas clouds observed at opposite sides of the nucleus, which we propose have been ejected in a previous AGN burst. The disc component velocity field is strongly disturbed by a large-scale bar. The subtraction of a velocity model combining both rotation and bar flows reveals three kinematic nuclear spiral arms: two in inflow and one in outflow. We estimate the mass inflow rate in the inner 180 pc obtaining \\dot{M}_{in} ≈ 1.5 × 10-2 M⊙ yr-1, about 160 times larger than the accretion rate necessary to power this AGN.

  7. Pion-nucleus scattering at around the DELTA (1232) resonance

    CERN Document Server

    Ahmed, H S; Rahman, M A; Rahman, S N

    2003-01-01

    The pion-nucleus scattering around 200 MeV and just above 1200 MeV is dominated by strong, broad DELTA (3,3) and weak resonances in the pi sup+-N interaction. The interaction to a first approximation can be described as diffraction process. Since it is well known that the strength of the pi sup + N and pi sup - N interactions are quite different from each other at the resonances, the analyses of differential cross section for pi sup + N and pi sup - N elastic scattering data in the region of low-lying pion-nucleus resonances will be a good test of different strengths. In the present work we analyze pions scattering from nuclei sup 9 Be, sup 2 sup 8 Si, sup 5 sup 8 Ni, sup 8 sup 9 Y and sup 2 sup 0 sup 8 Pb at incident pion energies between 50 and 291 MeV within the framework of the three parameter version of the Strong Absorption Model of Frahn and Venter. All the oscillations in the elastic scattering experimental data and for the experimental angular distribution leading to 2 sup + and 3 sup - collective st...

  8. Calcium signaling in synapse-to-nucleus communication.

    Science.gov (United States)

    Hagenston, Anna M; Bading, Hilmar

    2011-11-01

    Changes in the intracellular concentration of calcium ions in neurons are involved in neurite growth, development, and remodeling, regulation of neuronal excitability, increases and decreases in the strength of synaptic connections, and the activation of survival and programmed cell death pathways. An important aspect of the signals that trigger these processes is that they are frequently initiated in the form of glutamatergic neurotransmission within dendritic trees, while their completion involves specific changes in the patterns of genes expressed within neuronal nuclei. Accordingly, two prominent aims of research concerned with calcium signaling in neurons are determination of the mechanisms governing information conveyance between synapse and nucleus, and discovery of the rules dictating translation of specific patterns of inputs into appropriate and specific transcriptional responses. In this article, we present an overview of the avenues by which glutamatergic excitation of dendrites may be communicated to the neuronal nucleus and the primary calcium-dependent signaling pathways by which synaptic activity can invoke changes in neuronal gene expression programs.

  9. Cajal's contribution to the knowledge of the neuronal cell nucleus.

    Science.gov (United States)

    Lafarga, Miguel; Casafont, Iñigo; Bengoechea, Rocio; Tapia, Olga; Berciano, Maria T

    2009-08-01

    In 1906, the Spanish neurobiologist Santiago Ramón y Cajal was awarded the Nobel Prize in Physiology or Medicine in recognition of his work on the structure of neurons and their connections. Cajal is commonly regarded as the father of modern neuroscience. What is less well known is that Cajal also had a great interest in intracellular neuronal structures and developed the reduced silver nitrate method for the study of neurofibrils (neurofilaments) and nuclear subcompartments. It was in 1903 that Cajal discovered the "accessory body" ("Cajal body") and seven years later, published an article on the organization of the cell nucleus in mammalian neurons that represents a masterpiece of nuclear structure at the light microscopy level. In addition to the accessory body, it includes the analysis of several nuclear components currently recognized as fibrillar centers of the nucleolus, nuclear speckles of splicing factors, transcription foci, nuclear matrix, and the double nuclear membrane. The aim of this article is to revisit Cajal's contributions to the knowledge of the neuronal nucleus in light of our current understanding of nuclear structure and function.

  10. Inositide-specific phospholipase C signalling in the nucleus

    Directory of Open Access Journals (Sweden)

    FA Manzoli

    2009-12-01

    Full Text Available The nucleus of eukaryotic cells contains all the information needed for cell proliferation and differentiation, however the initiation of these programmes are dependent on the signalling pathway elicited by different agonists. The existence of a nuclear phosphoinositide signalling stems from the early evidence that isolated nuclei posses the lipid kinases capable of phosphorylating phosphatidylinositol (PI and phosphatidylinositol 4-phosphate (PIP. The synthesis of phosphatidylinositol 4,5- phosphate (PIP2 was clearly increased only in the nuclear fraction from Friend cells terminally differentiated towards erythrocytes (Cocco et al., 1987. On the contrary its amount along with that of PIP was decreased in nuclei of Swiss 3T3 cells stimulated to grow with insulin-like growth factor-I (IGFI (Manzoli et al., 1989. Following these early observations we and others have demonstrated in several cell type the participation of the whole phosphoinositide cycle in the nucleus (Cocco et al., 1994; Martelli et al., 1992; Divecha et al., 1991; Martelli et al., 1994; Mazzoni et al., 1992. Here we review the most recent achievements on this issue.

  11. Cerebellar fastigial nucleus influence on ipsilateral abducens activity during saccades.

    Science.gov (United States)

    Kojima, Yoshiko; Robinson, Farrel R; Soetedjo, Robijanto

    2014-04-01

    To characterize the cerebellar influence on neurons in the abducens (ABD) nucleus, we recorded ABD neurons before and after we inactivated the caudal part of the ipsilateral cerebellar fastigial nucleus (cFN) with muscimol injection. cFN activity influences the horizontal component of saccades. cFN inactivation increased the activity of most ipsilateral ABD neurons (19/22 in 2 monkeys) during ipsiversive (hypermetric) saccades, primarily by increasing burst duration. During contraversive (hypometric) saccades, the off-direction pause of most (10/15) ABD neurons was shorter than normal because of the early resumption of ABD activity. Early ABD firing caused the early contraction of antagonist muscles that reduced eye rotation and made contraversive saccades hypometric. Thus the cerebellum controls ipsilateral ABD activity by truncating on-direction bursts during ipsiversive saccades and extending off-direction pauses during contraversive saccades. We conclude that cFN output keeps saccades accurate by controlling when ABD on-direction bursts and off-direction pauses end.

  12. Tolerance to Sound Intensity of Binaural Coincidence Detection in the Nucleus Laminaris of the Owl

    OpenAIRE

    Peña, Jose Luis; Viete, Svenja; Albeck, Yehuda; Konishi, Masakazu

    1996-01-01

    Neurons of the owl's nucleus laminaris serve as coincidence detectors for measurement of interaural time difference. The discharge rate of nucleus laminaris neurons for both monaural and binaural stimulation increased with sound intensity until they reached an asymptote. Intense sounds affected neither the ratio between binaural and monaural responses nor the interaural time difference for which nucleus laminaris neurons were selective. Theoretical analysis showed that high afferent discharge...

  13. Intrinsic functional connectivity of the central nucleus of the amygdala and bed nucleus of the stria terminalis.

    Science.gov (United States)

    Gorka, Adam X; Torrisi, Salvatore; Shackman, Alexander J; Grillon, Christian; Ernst, Monique

    2017-04-06

    The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream targets that initiate defensive responses. Despite these commonalities, researchers have also proposed a functional dissociation between the CeA and BNST, with the CeA promoting responses to discrete stimuli and the BNST promoting responses to diffuse threat. Intrinsic functional connectivity (iFC) provides a means to investigate the functional architecture of the brain, unbiased by task demands. Using ultra-high field neuroimaging (7-Tesla fMRI), which provides increased spatial resolution, this study compared the iFC networks of the CeA and BNST in 27 healthy individuals. Both structures were coupled with areas of the medial prefrontal cortex, hippocampus, thalamus, and periaqueductal gray matter. Compared to the BNST, the bilateral CeA was more strongly coupled with the insula and regions that support sensory processing, including thalamus and fusiform gyrus. In contrast, the bilateral BNST was more strongly coupled with regions involved in cognitive and motivational processes, including the dorsal paracingulate gyrus, posterior cingulate cortex, and striatum. Collectively, these findings suggest that responses to sensory stimulation are preferentially coordinated by the CeA and cognitive and motivational responses are preferentially coordinated by the BNST. Published by Elsevier Inc.

  14. Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat

    Directory of Open Access Journals (Sweden)

    Jasper V. Smit

    2017-10-01

    Full Text Available Background Recently it has been shown in animal studies that deep brain stimulation (DBS of auditory structures was able to reduce tinnitus-like behavior. However, the question arises whether hearing might be impaired when interfering in auditory-related network loops with DBS. Methods The auditory brainstem response (ABR was measured in rats during high frequency stimulation (HFS and low frequency stimulation (LFS in the central nucleus of the inferior colliculus (CIC, n = 5 or dentate cerebellar nucleus (DCBN, n = 5. Besides hearing thresholds using ABR, relative measures of latency and amplitude can be extracted from the ABR. In this study ABR thresholds, interpeak latencies (I–III, III–V, I–V and V/I amplitude ratio were measured during off-stimulation state and during LFS and HFS. Results In both the CIC and the CNBN groups, no significant differences were observed for all outcome measures. Discussion DBS in both the CIC and the CNBN did not have adverse effects on hearing measurements. These findings suggest that DBS does not hamper physiological processing in the auditory circuitry.

  15. Deep brain stimulation of globus pallidus interna, subthalamic nucleus, and pedunculopontine nucleus for Parkinson's disease: which target?

    Science.gov (United States)

    Follett, Kenneth A; Torres-Russotto, Diego

    2012-01-01

    Deep brain stimulation (DBS) is an accepted therapy for people with Parkinson's disease (PD) motor symptoms that are refractory to pharmacologic therapy. Standard DBS targets are globus pallidus interna (GPi) and subthalamic nucleus (STN). The pedunculopontine nucleus (PPN) is being investigated as a novel target. Which target provides the best outcomes is unknown. The utility of GPi and STN as targets has been confirmed in numerous studies, including randomized comparisons of GPi DBS and STN DBS that demonstrated no difference in motor outcomes. DBS at either site improves appendicular motor symptoms, but beneficial effects on axial manifestations of PD such as postural instability or gait dysfunction (PIGD) are less apparent. PPN has been introduced as a DBS target due to failure of GPi and STN DBS to improve PIGD. Small observational studies indicate improved PIGD with PPN DBS, but small blinded trials show only subjective reduction in falls with no other impact on PIGD or other PD manifestations. No single DBS target is superior to the others. Each target offers relative advantages. Further studies are needed to better define the roles of each target, particularly PPN. Choice of target should be individualized according to providers' preferences and patients' needs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Generalized folding model for elastic and inelastic nucleus-nucleus scattering using realistic density dependent nucleon-nucleon interaction

    CERN Document Server

    Khoa, D T

    2000-01-01

    A generalized double-folding model for elastic and inelastic nucleus-nucleus scattering is presented. It is designed to accommodate effective nucleon-nucleon (NN) interactions that depend upon the density of nuclear matter in which the two nucleons are immersed. A recently parametrized density dependent M3Y interaction, based on the G-matrix elements of the Paris NN potential, has been used in the present folding calculation. The effects of knock-on exchange of the interacting nucleon pair are included in an accurate local approximation. Examples of the application of this model to study the refractive elastic and inelastic scattering data of sup 1 sup 2 C+ sup 1 sup 2 C and alpha+ sup 5 sup 8 sup , sup 6 sup 0 Ni systems are presented. A detailed comparison of the use of deformed optical potential (DP) and microscopic folded potential in the analysis of inelastic scattering has shown that the use of DP fails to reproduce the inelastic sup 1 sup 2 C+ sup 1 sup 2 C scattering data measured over a wide angular ...

  17. The Spectator-Induced Electromagnetic Effect on Meson Production in Nucleus-Nucleus Collisions at SPS Energies

    Directory of Open Access Journals (Sweden)

    Rybicki Andrzej

    2012-12-01

    Full Text Available The electromagnetic interaction between the spectator system and the charged mesons produced in the course of the high energy heavy ion collision was studied experimentally and theoretically in earlier works [1,2]. This effect was found to result in very large distortions of the final state spectra of the produced mesons [3] and to bring new information on the space-time evolution of the non-perturbative meson production process [4]. In this paper a more extended analysis of this effect will be presented, including a comparative study between charged meson spectra produced in Pb+Pb collisions as well as collisions of Pb ions with smaller nuclei. The experimental results will be compared with Monte Carlo simulations, giving a fair overall understanding of the interplay between the strong and the electromagnetic interaction in the heavy ion collision. A universal behaviour of charged meson spectra emerges from the above comparative study. This gives a unique chance of using the spectator charge as a tool to study the space-time evolution of the high energy nucleus-nucleus reaction.

  18. Study of the Pion Production Mechanisms in Nucleus-Nucleus Collisions at the CERN SC using the Omicron Spectrometer

    CERN Multimedia

    2002-01-01

    The aim of this experiment is to study the pion production mechanism in nucleus-nucleus collisions with the |3He and |1|2C beams of the CERN SC using the Omicron Spectrometer. The high intensity ion beams delivered now by the SC combined with the favourable characteristics of the Omicron Spectrometer offer a unique possibility of measuring very low cross-sections (typically in the order of 1 pb/(sr~MeV/c). In a first stage we will measure with an energy resolution of about 3~MeV the spectra of @p@+ emitted at 0|0 in two-body reactions induced by |3He ions of 910~MeV on targets of |6Li, |7Li, |9Be and |1|2C. The aim is to understand the reaction mechanisms and the nuclear wave functions most appropriate to describe the formation of nuclear bound states at momentum transfers of about 1.6@/1.7~GeV/c. The apparatus is shown in the figure. The same instrument will allow the measurement of the @p@+ inclusive spectra emitted at 0|0 after the interaction of the |1|2C|4|+ beam at 1032 MeV with the same targets. At 86 ...

  19. Tone Recognition of Continuous Mandarin Speech Based on Tone Nucleus Model and Neural Network

    Science.gov (United States)

    Wang, Xiao-Dong; Hirose, Keikichi; Zhang, Jin-Song; Minematsu, Nobuaki

    A method was developed for automatic recognition of syllable tone types in continuous speech of Mandarin by integrating two techniques, tone nucleus modeling and neural network classifier. The tone nucleus modeling considers a syllable F0 contour as consisting of three parts: onset course, tone nucleus, and offset course. Two courses are transitions from/to neighboring syllable F0 contours, while the tone nucleus is intrinsic part of the F0 contour. By viewing only the tone nucleus, acoustic features less affected by neighboring syllables are obtained. When using the tone nucleus modeling, automatic detection of tone nucleus comes crucial. An improvement was added to the original detection method. Distinctive acoustic features for tone types are not limited to F0 contours. Other prosodic features, such as waveform power and syllable duration, are also useful for tone recognition. Their heterogeneous features are rather difficult to be handled simultaneously in hidden Markov models (HMM), but are easy in neural networks. We adopted multi-layer perception (MLP) as a neural network. Tone recognition experiments were conducted for speaker dependent and independent cases. In order to show the effect of integration, experiments were conducted also for two baselines: HMM classifier with tone nucleus modeling, and MLP classifier viewing entire syllable instead of tone nucleus. The integrated method showed 87.1% of tone recognition rate in speaker dependent case, and 80.9% in speaker independent case, which was about 10% relative error reduction as compared to the baselines.

  20. IDENTIFICATION OF VESTIBULOOCULAR PROJECTION NEURONS IN THE DEVELOPING CHICKEN MEDIAL VESTIBULAR NUCLEUS

    Science.gov (United States)

    Gottesman-Davis, Adria; Peusner, Kenna D.

    2010-01-01

    Biocytin was injected into the oculomotor, trochlear, or abducens nucleus on one side using isolated chicken brainstem preparations or brain slices to identify the medial vestibular nucleus (MVN) neurons projecting to these targets. Oculomotor nucleus injections produced retrogradely labeled neurons in the contralateral ventrolateral MVN (MVNVL), with few labeled neurons in the ipsilateral MVNVL, and rarely in the dorsomedial MVN on either side. Labeled MVNVL neurons were identified as stellate (95%) and elongate cells (5%). Trochlear nucleus injections produced a similar pattern of MVN neuron labeling. Abducens nucleus injections resulted in retrogradely labeled stellate (87%) and elongate (13%) neurons in the MVNVL which had smaller cell bodies than those projecting to the oculomotor nucleus. Anteroposteriorly, labeled MVNVL neurons were coextensive with the tangential nucleus, with neurons projecting to the oculomotor nucleus distributed lateral to and intermixed with the more medially situated neurons projecting to the abducens nucleus. The fundamental pattern of vestibuloocular projecting neurons was similar at both embryonic ages studied, E16 and E13. In contrast to mammals, where most vestibuloocular projection neurons reside within the MVN, the majority of retrogradely labeled neurons in these chicken preparations were found within the ventrolateral vestibular, descending vestibular, and tangential nuclei. The morphological identification and mapping of vestibuloocular projection neurons in the chicken MVN described here represents the first step in a systematic evaluation of the relationship between avian vestibuloocular neuron structure and function. PMID:19705454

  1. Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor.

    Science.gov (United States)

    Johnston, Caitlin E; Herschel, Daniel J; Lasek, Amy W; Hammer, Ronald P; Nikulina, Ella M

    2015-02-01

    Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse.

  2. Progesterone turnover to its 5α-reduced metabolites in the ventral tegmental area of the midbrain is essential for initiating social and affective behavior and progesterone metabolism in female rats.

    Science.gov (United States)

    Frye, C A; Paris, J J

    2011-01-01

    Among women and female rodents, progesterone (P) influences social affiliation and affect. These effects may be partly due to formation of its 5α-reduced, 3α- hydroxylated metabolite, 5α-pregnan-3α-ol-20-one (3α,5α- THP). To elucidate whether actions of 3α,5α-THP in the midbrain ventral tegmental area (VTA) are both necessary and sufficient to enhance non-sexual and sexual social behaviors, affect, and central 3α,5α-THP metabolism. P and 3α,5α-THP formation were unperturbed or blocked in VTA via infusions of vehicle, PK11195 (400 ng), and/or indomethacin (10 μg). Rats then received subsequent infusions of vehicle or 3α,5α-THP (100 ng) and were assessed in a battery of tasks that included open field (exploration), elevated plus maze (anxiety behavior), social interaction (social affiliation), and paced mating (sexual behavior) or were not tested. Metabolic turnover of P to its 5α-reduced metabolites was assessed in plasma, midbrain, hippocampus, frontal cortex, diencephalon, and remaining subcortical tissues (control interbrain). Infusions of any combination of inhibitors significantly reduced social and affective behavior in all tasks compared to vehicle, concomitant with reduced turnover of P to its 5α-reduced metabolites, in midbrain only. Subsequent infusions of 3α,5α-THP significantly reinstated/enhanced anti- anxiety behavior, lordosis, and P turnover to its 5α-reduced metabolites in midbrain, as well as hippocampus, cortex, and diencephalon (but not plasma or interbrain). These data are the first to provide direct evidence that actions of 3α,5α-THP in the VTA are both necessary and sufficient for social and affective behavior, as well as initiation of central 5α-reduction.

  3. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    Science.gov (United States)

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system.

  4. A syndrome of the dentate nucleus mimicking psychogenic ataxia.

    Science.gov (United States)

    Salih, Farid; Breuer, Eva; Harnack, Daniel; Hoffmann, Karl-Titus; Ploner, Christoph J

    2010-03-15

    To date, cerebellar involvement in control of non-motor functions like cognition and emotion is increasingly well established. Current models suggest that motor and non-motor networks connecting the cerebellum with cortical areas operate independently in closed and segregated loops. Here, we report a 59-year-old female patient with a small cerebellar lesion that shows that cognitive activation can significantly influence cerebellar motor control. Surprisingly, this led to a clinical picture mimicking a psychogenic disorder. Similar to non-human primates, this case suggests that the human dentate nucleus consists of distinct cognitive and motor domains with additional somatotopical arrangement of the latter. Extending current models of cerebro-cerebellar interaction, this case further illustrates that there can be significant functional cross-talk between motor and cognitive cerebellar networks.

  5. Relativistic models for quasielastic electron and neutrino-nucleus scattering

    Directory of Open Access Journals (Sweden)

    Meucci Andrea

    2012-12-01

    Full Text Available Relativistic models developed within the framework of the impulse approximation for quasielastic (QE electron scattering and successfully tested in comparison with electron-scattering data have been extended to neutrino-nucleus scattering. Different descriptions of final-state interactions (FSI in the inclusive scattering are compared. In the relativistic Green’s function (RGF model FSI are described consistently with the exclusive scattering using a complex optical potential. In the relativistic mean field (RMF model FSI are described by the same RMF potential which gives the bound states. The results of the models are compared for electron and neutrino scattering and, for neutrino scattering, with the recently measured charged-current QE (CCQE MiniBooNE cross sections.

  6. Observation of Top Quark Production in Proton-Nucleus Collisions.

    Science.gov (United States)

    Sirunyan, A M; Tumasyan, A; Adam, W; Ambrogi, F; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Escalante Del Valle, A; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Grossmann, J; Hrubec, J; Jeitler, M; König, A; Krammer, N; Krätschmer, I; Liko, D; Madlener, T; Mikulec, I; Pree, E; Rad, N; Rohringer, H; Schieck, J; Schöfbeck, R; Spanring, M; Spitzbart, D; Waltenberger, W; Wittmann, J; Wulz, C-E; Zarucki, M; Chekhovsky, V; Mossolov, V; Suarez Gonzalez, J; De Wolf, E A; Di Croce, D; Janssen, X; Lauwers, J; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Abu Zeid, S; Blekman, F; D'Hondt, J; De Bruyn, I; De Clercq, J; Deroover, K; Flouris, G; Lontkovskyi, D; Lowette, S; Marchesini, I; Moortgat, S; Moreels, L; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Beghin, D; Bilin, B; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Dorney, B; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Kalsi, A K; Lenzi, T; Luetic, J; Maerschalk, T; Marinov, A; Seva, T; Starling, E; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Cornelis, T; Dobur, D; Fagot, A; Gul, M; Khvastunov, I; Poyraz, D; Roskas, C; Salva, S; Tytgat, M; Verbeke, W; Zaganidis, N; Bakhshiansohi, H; Bondu, O; Brochet, S; Bruno, G; Caputo, C; Caudron, A; David, P; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Piotrzkowski, K; Quertenmont, L; Saggio, A; Vidal Marono, M; Wertz, S; Zobec, J; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Correa Martins Junior, M; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Coelho, E; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Melo De Almeida, M; Mora Herrera, C; Mundim, L; Nogima, H; Sanchez Rosas, L J; Santoro, A; Sznajder, A; Thiel, M; Tonelli Manganote, E J; Torres Da Silva De Araujo, F; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Tomei, T R Fernandez Perez; Gregores, E M; Mercadante, P G; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Misheva, M; Rodozov, M; Shopova, M; Sultanov, G; Dimitrov, A; Litov, L; Pavlov, B; Petkov, P; Fang, W; Gao, X; Yuan, L; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Jiang, C H; Leggat, D; Liao, H; Liu, Z; Romeo, F; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Yazgan, E; Zhang, H; Zhang, S; Zhao, J; Ban, Y; Chen, G; Li, J; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Zhang, F; Wang, Y; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; González Hernández, C F; Ruiz Alvarez, J D; Segura Delgado, M A; Courbon, B; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Starodumov, A; Susa, T; Ather, M W; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Finger, M; Finger, M; Carrera Jarrin, E; Assran, Y; Elgammal, S; Mahrous, A; Dewanjee, R K; Kadastik, M; Perrini, L; Raidal, M; Tiko, A; Veelken, C; Eerola, P; Kirschenmann, H; Pekkanen, J; Voutilainen, M; Havukainen, J; Heikkilä, J K; Järvinen, T; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Laurila, S; Lehti, S; Lindén, T; Luukka, P; Siikonen, H; Tuominen, E; Tuominiemi, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Faure, J L; Ferri, F; Ganjour, S; Ghosh, S; Gras, P; Hamel de Monchenault, G; Jarry, P; Kucher, I; Leloup, C; Locci, E; Machet, M; Malcles, J; Negro, G; Rander, J; Rosowsky, A; Sahin, M Ö; Titov, M; Abdulsalam, A; Amendola, C; Antropov, I; Baffioni, S; Beaudette, F; Busson, P; Cadamuro, L; Charlot, C; Granier de Cassagnac, R; Jo, M; Lisniak, S; Lobanov, A; Martin Blanco, J; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Pigard, P; Salerno, R; Sauvan, J B; Sirois, Y; Stahl Leiton, A G; Strebler, T; Yilmaz, Y; Zabi, A; Zghiche, A; Agram, J-L; Andrea, J; Bloch, D; Brom, J-M; Buttignol, M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Coubez, X; Fontaine, J-C; Gelé, D; Goerlach, U; Jansová, M; Le Bihan, A-C; Tonon, N; Van Hove, P; Gadrat, S; Beauceron, S; Bernet, C; Boudoul, G; Chierici, R; Contardo, D; Depasse, P; El Mamouni, H; Fay, J; Finco, L; Gascon, S; Gouzevitch, M; Grenier, G; Ille, B; Lagarde, F; Laktineh, I B; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Popov, A; Sordini, V; Vander Donckt, M; Viret, S; Toriashvili, T; Bagaturia, I; Autermann, C; Feld, L; Kiesel, M K; Klein, K; Lipinski, M; Preuten, M; Schomakers, C; Schulz, J; Teroerde, M; Zhukov, V; Albert, A; Dietz-Laursonn, E; Duchardt, D; Endres, M; Erdmann, M; Erdweg, S; Esch, T; Fischer, R; Güth, A; Hamer, M; Hebbeker, T; Heidemann, C; Hoepfner, K; Knutzen, S; Merschmeyer, M; Meyer, A; Millet, P; Mukherjee, S; Pook, T; Radziej, M; Reithler, H; Rieger, M; Scheuch, F; Teyssier, D; Thüer, S; Flügge, G; Kargoll, B; Kress, T; Künsken, A; Müller, T; Nehrkorn, A; Nowack, A; Pistone, C; Pooth, O; Stahl, A; Aldaya Martin, M; Arndt, T; Asawatangtrakuldee, C; Beernaert, K; Behnke, O; Behrens, U; Bermúdez Martínez, A; Bin Anuar, A A; Borras, K; Botta, V; Campbell, A; Connor, P; Contreras-Campana, C; Costanza, F; Diez Pardos, C; Eckerlin, G; Eckstein, D; Eichhorn, T; Eren, E; Gallo, E; Garay Garcia, J; Geiser, A; Grados Luyando, J M; Grohsjean, A; Gunnellini, P; Guthoff, M; Harb, A; Hauk, J; Hempel, M; Jung, H; Kasemann, M; Keaveney, J; Kleinwort, C; Korol, I; Krücker, D; Lange, W; Lelek, A; Lenz, T; Leonard, J; Lipka, K; Lohmann, W; Mankel, R; Melzer-Pellmann, I-A; Meyer, A B; Mittag, G; Mnich, J; Mussgiller, A; Ntomari, E; Pitzl, D; Raspereza, A; Savitskyi, M; Saxena, P; Shevchenko, R; Stefaniuk, N; Van Onsem, G P; Walsh, R; Wen, Y; Wichmann, K; Wissing, C; Zenaiev, O; Aggleton, R; Bein, S; Blobel, V; Centis Vignali, M; Dreyer, T; Garutti, E; Gonzalez, D; Haller, J; Hinzmann, A; Hoffmann, M; Karavdina, A; Klanner, R; Kogler, R; Kovalchuk, N; Kurz, S; Lapsien, T; Marconi, D; Meyer, M; Niedziela, M; Nowatschin, D; Pantaleo, F; Peiffer, T; Perieanu, A; Scharf, C; Schleper, P; Schmidt, A; Schumann, S; Schwandt, J; Sonneveld, J; Stadie, H; Steinbrück, G; Stober, F M; Stöver, M; Tholen, H; Troendle, D; Usai, E; Vanhoefer, A; Vormwald, B; Akbiyik, M; Barth, C; Baselga, M; Baur, S; Butz, E; Caspart, R; Chwalek, T; Colombo, F; De Boer, W; Dierlamm, A; Faltermann, N; Freund, B; Friese, R; Giffels, M; Harrendorf, M A; Hartmann, F; Heindl, S M; Husemann, U; Kassel, F; Kudella, S; Mildner, H; Mozer, M U; Müller, Th; Plagge, M; Quast, G; Rabbertz, K; Schröder, M; Shvetsov, I; Sieber, G; Simonis, H J; Ulrich, R; Wayand, S; Weber, M; Weiler, T; Williamson, S; Wöhrmann, C; Wolf, R; Anagnostou, G; Daskalakis, G; Geralis, T; Kyriakis, A; Loukas, D; Topsis-Giotis, I; Karathanasis, G; Kesisoglou, S; Panagiotou, A; Saoulidou, N; Kousouris, K; Evangelou, I; Foudas, C; Gianneios, P; Katsoulis, P; Kokkas, P; Mallios, S; Manthos, N; Papadopoulos, I; Paradas, E; Strologas, J; Triantis, F A; Tsitsonis, D; Csanad, M; Filipovic, N; Pasztor, G; Surányi, O; Veres, G I; Bencze, G; Hajdu, C; Horvath, D; Hunyadi, Á; Sikler, F; Veszpremi, V; Beni, N; Czellar, S; Karancsi, J; Makovec, A; Molnar, J; Szillasi, Z; Bartók, M; Raics, P; Trocsanyi, Z L; Ujvari, B; Choudhury, S; Komaragiri, J R; Bahinipati, S; Bhowmik, S; Mal, P; Mandal, K; Nayak, A; Sahoo, D K; Sahoo, N; Swain, S K; Bansal, S; Beri, S B; Bhatnagar, V; Chawla, R; Dhingra, N; Kaur, A; Kaur, M; Kaur, S; Kumar, R; Kumari, P; Mehta, A; Singh, J B; Walia, G; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A; Chauhan, S; Choudhary, B C; Garg, R B; Keshri, S; Kumar, A; Malhotra, S; Naimuddin, M; Ranjan, K; Sharma, R; Bhardwaj, R; Bhattacharya, R; Bhattacharya, S; Bhawandeep, U; Dey, S; Dutt, S; Dutta, S; Ghosh, S; Majumdar, N; Modak, A; Mondal, K; Mukhopadhyay, S; Nandan, S; Purohit, A; Roy, A; Roy Chowdhury, S; Sarkar, S; Sharan, M; Thakur, S; Behera, P K; Chudasama, R; Dutta, D; Jha, V; Kumar, V; Mohanty, A K; Netrakanti, P K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Dugad, S; Mahakud, B; Mitra, S; Mohanty, G B; Sur, N; Sutar, B; Banerjee, S; Bhattacharya, S; Chatterjee, S; Das, P; Guchait, M; Jain, Sa; Kumar, S; Maity, M; Majumder, G; Mazumdar, K; Sarkar, T; Wickramage, N; Chauhan, S; Dube, S; Hegde, V; Kapoor, A; Kothekar, K; Pandey, S; Rane, A; Sharma, S; Chenarani, S; Eskandari Tadavani, E; Etesami, S M; Khakzad, M; Mohammadi Najafabadi, M; Naseri, M; Paktinat Mehdiabadi, S; Rezaei Hosseinabadi, F; Safarzadeh, B; Zeinali, M; Felcini, M; Grunewald, M; Abbrescia, M; Calabria, C; Colaleo, A; Creanza, D; Cristella, L; De Filippis, N; De Palma, M; Errico, F; Fiore, L; Iaselli, G; Lezki, S; Maggi, G; Maggi, M; Miniello, G; My, S; Nuzzo, S; Pompili, A; Pugliese, G; Radogna, R; Ranieri, A; Selvaggi, G; Sharma, A; Silvestris, L; Venditti, R; Verwilligen, P; Abbiendi, G; Battilana, C; Bonacorsi, D; Borgonovi, L; Braibant-Giacomelli, S; Campanini, R; Capiluppi, P; Castro, A; Cavallo, F R; Chhibra, S S; Codispoti, G; Cuffiani, M; Dallavalle, G M; Fabbri, F; Fanfani, A; Fasanella, D; Giacomelli, P; Grandi, C; Guiducci, L; Marcellini, S; Masetti, G; Montanari, A; Navarria, F L; Perrotta, A; Rossi, A M; Rovelli, T; Siroli, G P; Tosi, N; Albergo, S; Costa, S; Di Mattia, A; Giordano, F; Potenza, R; Tricomi, A; Tuve, C; Barbagli, G; Chatterjee, K; Ciulli, V; Civinini, C; D'Alessandro, R; Focardi, E; Lenzi, P; Meschini, M; Paoletti, S; Russo, L; Sguazzoni, G; Strom, D; Viliani, L; Benussi, L; Bianco, S; Fabbri, F; Piccolo, D; Primavera, F; Calvelli, V; Ferro, F; Ravera, F; Robutti, E; Tosi, S; Benaglia, A; Beschi, A; Brianza, L; Brivio, F; Ciriolo, V; Dinardo, M E; Fiorendi, S; Gennai, S; Ghezzi, A; Govoni, P; Malberti, M; Malvezzi, S; Manzoni, R A; Menasce, D; Moroni, L; Paganoni, M; Pauwels, K; Pedrini, D; Pigazzini, S; Ragazzi, S; Tabarelli de Fatis, T; Buontempo, S; Cavallo, N; Di Guida, S; Fabozzi, F; Fienga, F; Iorio, A O M; Khan, W A; Lista, L; Meola, S; Paolucci, P; Sciacca, C; Thyssen, F; Azzi, P; Bacchetta, N; Benato, L; Bisello, D; Boletti, A; Carlin, R; Carvalho Antunes De Oliveira, A; Checchia, P; De Castro Manzano, P; Dorigo, T; Dosselli, U; Gasparini, F; Gasparini, U; Gozzelino, A; Lacaprara, S; Margoni, M; Meneguzzo, A T; Pozzobon, N; Ronchese, P; Rossin, R; Simonetto, F; Torassa, E; Zanetti, M; Zotto, P; Zumerle, G; Braghieri, A; Magnani, A; Montagna, P; Ratti, S P; Re, V; Ressegotti, M; Riccardi, C; Salvini, P; Vai, I; Vitulo, P; Alunni Solestizi, L; Biasini, M; Bilei, G M; Cecchi, C; Ciangottini, D; Fanò, L; Leonardi, R; Manoni, E; Mantovani, G; Mariani, V; Menichelli, M; Rossi, A; Santocchia, A; Spiga, D; Androsov, K; Azzurri, P; Bagliesi, G; Boccali, T; Borrello, L; Castaldi, R; Ciocci, M A; Dell'Orso, R; Fedi, G; Giannini, L; Giassi, A; Grippo, M T; Ligabue, F; Lomtadze, T; Manca, E; Mandorli, G; Messineo, A; Palla, F; Rizzi, A; Savoy-Navarro, A; Spagnolo, P; Tenchini, R; Tonelli, G; Venturi, A; Verdini, P G; Barone, L; Cavallari, F; Cipriani, M; Daci, N; Del Re, D; Di Marco, E; Diemoz, M; Gelli, S; Longo, E; Margaroli, F; Marzocchi, B; Meridiani, P; Organtini, G; Paramatti, R; Preiato, F; Rahatlou, S; Rovelli, C; Santanastasio, F; Amapane, N; Arcidiacono, R; Argiro, S; Arneodo, M; Bartosik, N; Bellan, R; Biino, C; Cartiglia, N; Cenna, F; Costa, M; Covarelli, R; Degano, A; Demaria, N; Kiani, B; Mariotti, C; Maselli, S; Migliore, E; Monaco, V; Monteil, E; Monteno, M; Obertino, M M; Pacher, L; Pastrone, N; Pelliccioni, M; Pinna Angioni, G L; Romero, A; Ruspa, M; Sacchi, R; Shchelina, K; Sola, V; Solano, A; Staiano, A; Traczyk, P; Belforte, S; Casarsa, M; Cossutti, F; Della Ricca, G; Zanetti, A; Kim, D H; Kim, G N; Kim, M S; Lee, J; Lee, S; Lee, S W; Moon, C S; Oh, Y D; Sekmen, S; Son, D C; Yang, Y C; Lee, A; Kim, H; Moon, D H; Oh, G; Brochero Cifuentes, J A; Goh, J; Kim, T J; Cho, S; Choi, S; Go, Y; Gyun, D; Ha, S; Hong, B; Jo, Y; Kim, Y; Lee, K; Lee, K S; Lee, S; Lim, J; Park, S K; Roh, Y; Almond, J; Kim, J; Kim, J S; Lee, H; Lee, K; Nam, K; Oh, S B; Radburn-Smith, B C; Seo, S H; Yang, U K; Yoo, H D; Yu, G B; Kim, H; Kim, J H; Lee, J S H; Park, I C; Choi, Y; Hwang, C; Lee, J; Yu, I; Dudenas, V; Juodagalvis, A; Vaitkus, J; Ahmed, I; Ibrahim, Z A; Md Ali, M A B; Mohamad Idris, F; Wan Abdullah, W A T; Yusli, M N; Zolkapli, Z; Reyes-Almanza, R; Ramirez-Sanchez, G; Duran-Osuna, M C; Castilla-Valdez, H; De La Cruz-Burelo, E; Heredia-De La Cruz, I; Rabadan-Trejo, R I; Lopez-Fernandez, R; Mejia Guisao, J; Sanchez-Hernandez, A; Carrillo Moreno, S; Oropeza Barrera, C; Vazquez Valencia, F; Eysermans, J; Pedraza, I; Salazar Ibarguen, H A; Uribe Estrada, C; Morelos Pineda, A; Krofcheck, D; Butler, P H; Ahmad, A; Ahmad, M; Hassan, Q; Hoorani, H R; Saddique, A; Shah, M A; Shoaib, M; Waqas, M; Bialkowska, H; Bluj, M; Boimska, B; Frueboes, T; Górski, M; Kazana, M; Nawrocki, K; Szleper, M; Zalewski, P; Bunkowski, K; Byszuk, A; Doroba, K; Kalinowski, A; Konecki, M; Krolikowski, J; Misiura, M; Olszewski, M; Pyskir, A; Walczak, M; Bargassa, P; Beirão Da Cruz E Silva, C; Di Francesco, A; Faccioli, P; Galinhas, B; Gallinaro, M; Hollar, J; Leonardo, N; Lloret Iglesias, L; Nemallapudi, M V; Seixas, J; Strong, G; Toldaiev, O; Vadruccio, D; Varela, J; Afanasiev, S; Bunin, P; Gavrilenko, M; Golutvin, I; Gorbunov, I; Kamenev, A; Karjavin, V; Lanev, A; Malakhov, A; Matveev, V; Palichik, V; Perelygin, V; Shmatov, S; Shulha, S; Skatchkov, N; Smirnov, V; Voytishin, N; Zarubin, A; Ivanov, Y; Kim, V; Kuznetsova, E; Levchenko, P; Murzin, V; Oreshkin, V; Smirnov, I; Sosnov, D; Sulimov, V; Uvarov, L; Vavilov, S; Vorobyev, A; Andreev, Yu; Dermenev, A; Gninenko, S; Golubev, N; Karneyeu, A; Kirsanov, M; Krasnikov, N; Pashenkov, A; Tlisov, D; Toropin, A; Epshteyn, V; Gavrilov, V; Lychkovskaya, N; Popov, V; Pozdnyakov, I; Safronov, G; Spiridonov, A; Stepennov, A; Toms, M; Vlasov, E; Zhokin, A; Aushev, T; Bylinkin, A; Chistov, R; Danilov, M; Parygin, P; Philippov, D; Polikarpov, S; Tarkovskii, E; Andreev, V; Azarkin, M; Dremin, I; Kirakosyan, M; Terkulov, A; Baskakov, A; Belyaev, A; Boos, E; Dudko, L; Ershov, A; Gribushin, A; Kodolova, O; Korotkikh, V; Lokhtin, I; Miagkov, I; Obraztsov, S; Petrushanko, S; Savrin, V; Snigirev, A; Vardanyan, I; Blinov, V; Skovpen, Y; Shtol, D; Azhgirey, I; Bayshev, I; Bitioukov, S; Elumakhov, D; Godizov, A; Kachanov, V; Kalinin, A; Konstantinov, D; Mandrik, P; Petrov, V; Ryutin, R; Sobol, A; Troshin, S; Tyurin, N; Uzunian, A; Volkov, A; Adzic, P; Cirkovic, P; Devetak, D; Dordevic, M; Milosevic, J; Rekovic, V; Alcaraz Maestre, J; Bachiller, I; Barrio Luna, M; Cerrada, M; Colino, N; De La Cruz, B; Delgado Peris, A; Fernandez Bedoya, C; Fernández Ramos, J P; Flix, J; Fouz, M C; Gonzalez Lopez, O; Goy Lopez, S; Hernandez, J M; Josa, M I; Moran, D; Pérez-Calero Yzquierdo, A; Puerta Pelayo, J; Quintario Olmeda, A; Redondo, I; Romero, L; Soares, M S; Álvarez Fernández, A; Albajar, C; de Trocóniz, J F; Missiroli, M; Cuevas, J; Erice, C; Fernandez Menendez, J; Gonzalez Caballero, I; González Fernández, J R; Palencia Cortezon, E; Sanchez Cruz, S; Vischia, P; Vizan Garcia, J M; Cabrillo, I J; Calderon, A; Chazin Quero, B; Curras, E; Duarte Campderros, J; Fernandez, M; Garcia-Ferrero, J; Gomez, G; Lopez Virto, A; Marco, J; Martinez Rivero, C; Martinez Ruiz Del Arbol, P; Matorras, F; Piedra Gomez, J; Rodrigo, T; Ruiz-Jimeno, A; Scodellaro, L; Trevisani, N; Vila, I; Vilar Cortabitarte, R; Abbaneo, D; Akgun, B; Auffray, E; Baillon, P; Ball, A H; Barney, D; Bendavid, J; Bianco, M; Bloch, P; Bocci, A; Botta, C; Camporesi, T; Castello, R; Cepeda, M; Cerminara, G; Chapon, E; Chen, Y; d'Enterria, D; Dabrowski, A; Daponte, V; David, A; De Gruttola, M; De Roeck, A; Deelen, N; Dobson, M; du Pree, T; Dünser, M; Dupont, N; Elliott-Peisert, A; Everaerts, P; Fallavollita, F; Franzoni, G; Fulcher, J; Funk, W; Gigi, D; Gilbert, A; Gill, K; Glege, F; Gulhan, D; Harris, P; Hegeman, J; Innocente, V; Jafari, A; Janot, P; Karacheban, O; Kieseler, J; Knünz, V; Kornmayer, A; Kortelainen, M J; Krammer, M; Lange, C; Lecoq, P; Lourenço, C; Lucchini, M T; Malgeri, L; Mannelli, M; Martelli, A; Meijers, F; Merlin, J A; Mersi, S; Meschi, E; Milenovic, P; Moortgat, F; Mulders, M; Neugebauer, H; Ngadiuba, J; Orfanelli, S; Orsini, L; Pape, L; Perez, E; Peruzzi, M; Petrilli, A; Petrucciani, G; Pfeiffer, A; Pierini, M; Rabady, D; Racz, A; Reis, T; Rolandi, G; Rovere, M; Sakulin, H; Schäfer, C; Schwick, C; Seidel, M; Selvaggi, M; Sharma, A; Silva, P; Sphicas, P; Stakia, A; Steggemann, J; Stoye, M; Tosi, M; Treille, D; Triossi, A; Tsirou, A; Veckalns, V; Verweij, M; Zeuner, W D; Bertl, W; Caminada, L; Deiters, K; Erdmann, W; Horisberger, R; Ingram, Q; Kaestli, H C; Kotlinski, D; Langenegger, U; Rohe, T; Wiederkehr, S A; Backhaus, M; Bäni, L; Berger, P; Bianchini, L; Casal, B; Dissertori, G; Dittmar, M; Donegà, M; Dorfer, C; Grab, C; Heidegger, C; Hits, D; Hoss, J; Kasieczka, G; Klijnsma, T; Lustermann, W; Mangano, B; Marionneau, M; Meinhard, M T; Meister, D; Micheli, F; Musella, P; Nessi-Tedaldi, F; Pandolfi, F; Pata, J; Pauss, F; Perrin, G; Perrozzi, L; Quittnat, M; Reichmann, M; Sanz Becerra, D A; Schönenberger, M; Shchutska, L; Tavolaro, V R; Theofilatos, K; Vesterbacka Olsson, M L; Wallny, R; Zhu, D H; Aarrestad, T K; Amsler, C; Canelli, M F; De Cosa, A; Del Burgo, R; Donato, S; Galloni, C; Hreus, T; Kilminster, B; Pinna, D; Rauco, G; Robmann, P; Salerno, D; Schweiger, K; Seitz, C; Takahashi, Y; Zucchetta, A; Candelise, V; Chang, Y H; Cheng, K Y; Doan, T H; Jain, Sh; Khurana, R; Kuo, C M; Lin, W; Pozdnyakov, A; Yu, S S; Kumar, Arun; Chang, P; Chao, Y; Chen, K F; Chen, P H; Fiori, F; Hou, W-S; Hsiung, Y; Liu, Y F; Lu, R-S; Paganis, E; Psallidas, A; Steen, A; Tsai, J F; Asavapibhop, B; Kovitanggoon, K; Singh, G; Srimanobhas, N; Bat, A; Boran, F; Cerci, S; Damarseckin, S; Demiroglu, Z S; Dozen, C; Dumanoglu, I; Girgis, S; Gokbulut, G; Guler, Y; Hos, I; Kangal, E E; Kara, O; Kayis Topaksu, A; Kiminsu, U; Oglakci, M; Onengut, G; Ozdemir, K; Sunar Cerci, D; Tali, B; Tok, U G; Turkcapar, S; Zorbakir, I S; Zorbilmez, C; Karapinar, G; Ocalan, K; Yalvac, M; Zeyrek, M; Gülmez, E; Kaya, M; Kaya, O; Tekten, S; Yetkin, E A; Agaras, M N; Atay, S; Cakir, A; Cankocak, K; Köseoglu, I; Grynyov, B; Levchuk, L; Ball, F; Beck, L; Brooke, J J; Burns, D; Clement, E; Cussans, D; Davignon, O; Flacher, H; Goldstein, J; Heath, G P; Heath, H F; Kreczko, L; Newbold, D M; Paramesvaran, S; Sakuma, T; Seif El Nasr-Storey, S; Smith, D; Smith, V J; Belyaev, A; Brew, C; Brown, R M; Calligaris, L; Cieri, D; Cockerill, D J A; Coughlan, J A; Harder, K; Harper, S; Linacre, J; Olaiya, E; Petyt, D; Shepherd-Themistocleous, C H; Thea, A; Tomalin, I R; Williams, T; Auzinger, G; Bainbridge, R; Borg, J; Breeze, S; Buchmuller, O; Bundock, A; Casasso, S; Citron, M; Colling, D; Corpe, L; Dauncey, P; Davies, G; De Wit, A; Della Negra, M; Di Maria, R; Elwood, A; Haddad, Y; Hall, G; Iles, G; James, T; Lane, R; Laner, C; Lyons, L; Magnan, A-M; Malik, S; Mastrolorenzo, L; Matsushita, T; Nash, J; Nikitenko, A; Palladino, V; Pesaresi, M; Raymond, D M; Richards, A; Rose, A; Scott, E; Seez, C; Shtipliyski, A; Summers, S; Tapper, A; Uchida, K; Vazquez Acosta, M; Virdee, T; Wardle, N; Winterbottom, D; Wright, J; Zenz, S C; Cole, J E; Hobson, P R; Khan, A; Kyberd, P; Reid, I D; Teodorescu, L; Zahid, S; Borzou, A; Call, K; Dittmann, J; Hatakeyama, K; Liu, H; Pastika, N; Smith, C; Bartek, R; Dominguez, A; Buccilli, A; Cooper, S I; Henderson, C; Rumerio, P; West, C; Arcaro, D; Avetisyan, A; Bose, T; Gastler, D; Rankin, D; Richardson, C; Rohlf, J; Sulak, L; Zou, D; Benelli, G; Cutts, D; Garabedian, A; Hadley, M; Hakala, J; Heintz, U; Hogan, J M; Kwok, K H M; Laird, E; Landsberg, G; Lee, J; Mao, Z; Narain, M; Pazzini, J; Piperov, S; Sagir, S; Syarif, R; Yu, D; Band, R; Brainerd, C; Burns, D; Calderon De La Barca Sanchez, M; Chertok, M; Conway, J; Conway, R; Cox, P T; Erbacher, R; Flores, C; Funk, G; Ko, W; Lander, R; Mclean, C; Mulhearn, M; Pellett, D; Pilot, J; Shalhout, S; Shi, M; Smith, J; Stolp, D; Tos, K; Tripathi, M; Wang, Z; Bachtis, M; Bravo, C; Cousins, R; Dasgupta, A; Florent, A; Hauser, J; Ignatenko, M; Mccoll, N; Regnard, S; Saltzberg, D; Schnaible, C; Valuev, V; Bouvier, E; Burt, K; Clare, R; Ellison, J; Gary, J W; Ghiasi Shirazi, S M A; Hanson, G; Heilman, J; Karapostoli, G; Kennedy, E; Lacroix, F; Long, O R; Olmedo Negrete, M; Paneva, M I; Si, W; Wang, L; Wei, H; Wimpenny, S; Yates, B R; Branson, J G; Cittolin, S; Derdzinski, M; Gerosa, R; Gilbert, D; Hashemi, B; Holzner, A; Klein, D; Kole, G; Krutelyov, V; Letts, J; Masciovecchio, M; Olivito, D; Padhi, S; Pieri, M; Sani, M; Sharma, V; Tadel, M; Vartak, A; Wasserbaech, S; Wood, J; Würthwein, F; Yagil, A; Zevi Della Porta, G; Amin, N; Bhandari, R; Bradmiller-Feld, J; Campagnari, C; Dishaw, A; Dutta, V; Franco Sevilla, M; Gouskos, L; Heller, R; Incandela, J; Ovcharova, A; Qu, H; Richman, J; Stuart, D; Suarez, I; Yoo, J; Anderson, D; Bornheim, A; Lawhorn, J M; Newman, H B; Nguyen, T Q; Pena, C; Spiropulu, M; Vlimant, J R; Xie, S; Zhang, Z; Zhu, R Y; Andrews, M B; Ferguson, T; Mudholkar, T; Paulini, M; Russ, J; Sun, M; Vogel, H; Vorobiev, I; Weinberg, M; Cumalat, J P; Ford, W T; Jensen, F; Johnson, A; Krohn, M; Leontsinis, S; Mulholland, T; Stenson, K; Wagner, S R; Alexander, J; Chaves, J; Chu, J; Dittmer, S; Mcdermott, K; Mirman, N; Patterson, J R; Quach, D; Rinkevicius, A; Ryd, A; Skinnari, L; Soffi, L; Tan, S M; Tao, Z; Thom, J; Tucker, J; Wittich, P; Zientek, M; Abdullin, S; Albrow, M; Alyari, M; Apollinari, G; Apresyan, A; Apyan, A; Banerjee, S; Bauerdick, L A T; Beretvas, A; Berryhill, J; Bhat, P C; Bolla, G; Burkett, K; Butler, J N; Canepa, A; Cerati, G B; Cheung, H W K; Chlebana, F; Cremonesi, M; Duarte, J; Elvira, V D; Freeman, J; Gecse, Z; Gottschalk, E; Gray, L; Green, D; Grünendahl, S; Gutsche, O; Harris, R M; Hasegawa, S; Hirschauer, J; Hu, Z; Jayatilaka, B; Jindariani, S; Johnson, M; Joshi, U; Klima, B; Kreis, B; Lammel, S; Lincoln, D; Lipton, R; Liu, M; Liu, T; Lopes De Sá, R; Lykken, J; Maeshima, K; Magini, N; Marraffino, J M; Mason, D; McBride, P; Merkel, P; Mrenna, S; Nahn, S; O'Dell, V; Pedro, K; Prokofyev, O; Rakness, G; Ristori, L; Schneider, B; Sexton-Kennedy, E; Soha, A; Spalding, W J; Spiegel, L; Stoynev, S; Strait, J; Strobbe, N; Taylor, L; Tkaczyk, S; Tran, N V; Uplegger, L; Vaandering, E W; Vernieri, C; Verzocchi, M; Vidal, R; Wang, M; Weber, H A; Whitbeck, A; Acosta, D; Avery, P; Bortignon, P; Bourilkov, D; Brinkerhoff, A; Carnes, A; Carver, M; Curry, D; Field, R D; Furic, I K; Gleyzer, S V; Joshi, B M; Konigsberg, J; Korytov, A; Kotov, K; Ma, P; Matchev, K; Mei, H; Mitselmakher, G; Shi, K; Sperka, D; Terentyev, N; Thomas, L; Wang, J; Wang, S; Yelton, J; Joshi, Y R; Linn, S; Markowitz, P; Rodriguez, J L; Ackert, A; Adams, T; Askew, A; Hagopian, S; Hagopian, V; Johnson, K F; Kolberg, T; Martinez, G; Perry, T; Prosper, H; Saha, A; Santra, A; Sharma, V; Yohay, R; Baarmand, M M; Bhopatkar, V; Colafranceschi, S; Hohlmann, M; Noonan, D; Roy, T; Yumiceva, F; Adams, M R; Apanasevich, L; Berry, D; Betts, R R; Cavanaugh, R; Chen, X; Evdokimov, O; Gerber, C E; Hangal, D A; Hofman, D J; Jung, K; Kamin, J; Sandoval Gonzalez, I D; Tonjes, M B; Trauger, H; Varelas, N; Wang, H; Wu, Z; Zhang, J; Bilki, B; Clarida, W; Dilsiz, K; Durgut, S; Gandrajula, R P; Haytmyradov, M; Khristenko, V; Merlo, J-P; Mermerkaya, H; Mestvirishvili, A; Moeller, A; Nachtman, J; Ogul, H; Onel, Y; Ozok, F; Penzo, A; Snyder, C; Tiras, E; Wetzel, J; Yi, K; Blumenfeld, B; Cocoros, A; Eminizer, N; Fehling, D; Feng, L; Gritsan, A V; Maksimovic, P; Roskes, J; Sarica, U; Swartz, M; Xiao, M; You, C; Al-Bataineh, A; Baringer, P; Bean, A; Boren, S; Bowen, J; Castle, J; Khalil, S; Kropivnitskaya, A; Majumder, D; Mcbrayer, W; Murray, M; Rogan, C; Royon, C; Sanders, S; Schmitz, E; Tapia Takaki, J D; Wang, Q; Ivanov, A; Kaadze, K; Maravin, Y; Mohammadi, A; Saini, L K; Skhirtladze, N; Rebassoo, F; Wright, D; Baden, A; Baron, O; Belloni, A; Eno, S C; Feng, Y; Ferraioli, C; Hadley, N J; Jabeen, S; Jeng, G Y; Kellogg, R G; Kunkle, J; Mignerey, A C; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonwar, S C; Abercrombie, D; Allen, B; Azzolini, V; Barbieri, R; Baty, A; Bi, R; Brandt, S; Busza, W; Cali, I A; D'Alfonso, M; Demiragli, Z; Gomez Ceballos, G; Goncharov, M; Hsu, D; Hu, M; Iiyama, Y; Innocenti, G M; Klute, M; Kovalskyi, D; Lee, Y-J; Levin, A; Luckey, P D; Maier, B; Marini, A C; Mcginn, C; Mironov, C; Narayanan, S; Niu, X; Paus, C; Roland, C; Roland, G; Salfeld-Nebgen, J; Stephans, G S F; Tatar, K; Velicanu, D; Wang, J; Wang, T W; Wyslouch, B; Benvenuti, A C; Chatterjee, R M; Evans, A; Hansen, P; Hiltbrand, J; Kalafut, S; Kubota, Y; Lesko, Z; Mans, J; Nourbakhsh, S; Ruckstuhl, N; Rusack, R; Turkewitz, J; Wadud, M A; Acosta, J G; Oliveros, S; Avdeeva, E; Bloom, K; Claes, D R; Fangmeier, C; Golf, F; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Monroy, J; Siado, J E; Snow, G R; Stieger, B; Dolen, J; Godshalk, A; Harrington, C; Iashvili, I; Nguyen, D; Parker, A; Rappoccio, S; Roozbahani, B; Alverson, G; Barberis, E; Freer, C; Hortiangtham, A; Massironi, A; Morse, D M; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wamorkar, T; Wang, B; Wisecarver, A; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Mucia, N; Odell, N; Schmitt, M H; Sung, K; Trovato, M; Velasco, M; Bucci, R; Dev, N; Hildreth, M; Hurtado Anampa, K; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Li, W; Loukas, N; Marinelli, N; Meng, F; Mueller, C; Musienko, Y; Planer, M; Reinsvold, A; Ruchti, R; Siddireddy, P; Smith, G; Taroni, S; Wayne, M; Wightman, A; Wolf, M; Woodard, A; Alimena, J; Antonelli, L; Bylsma, B; Durkin, L S; Flowers, S; Francis, B; Hart, A; Hill, C; Ji, W; Liu, B; Luo, W; Winer, B L; Wulsin, H W; Cooperstein, S; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Higginbotham, S; Kalogeropoulos, A; Lange, D; Luo, J; Marlow, D; Mei, K; Ojalvo, I; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Tully, C; Malik, S; Norberg, S; Barker, A; Barnes, V E; Das, S; Folgueras, S; Gutay, L; Jones, M; Jung, A W; Khatiwada, A; Miller, D H; Neumeister, N; Peng, C C; Qiu, H; Schulte, J F; Sun, J; Wang, F; Xiao, R; Xie, W; Cheng, T; Parashar, N; Stupak, J; Chen, Z; Ecklund, K M; Freed, S; Geurts, F J M; Guilbaud, M; Kilpatrick, M; Li, W; Michlin, B; Padley, B P; Roberts, J; Rorie, J; Shi, W; Tu, Z; Zabel, J; Zhang, A; Bodek, A; de Barbaro, P; Demina, R; Duh, Y T; Ferbel, T; Galanti, M; Garcia-Bellido, A; Han, J; Hindrichs, O; Khukhunaishvili, A; Lo, K H; Tan, P; Verzetti, M; Ciesielski, R; Goulianos, K; Mesropian, C; Agapitos, A; Chou, J P; Gershtein, Y; Gómez Espinosa, T A; Halkiadakis, E; Heindl, M; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Kyriacou, S; Lath, A; Montalvo, R; Nash, K; Osherson, M; Saka, H; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Delannoy, A G; Heideman, J; Riley, G; Rose, K; Spanier, S; Thapa, K; Bouhali, O; Castaneda Hernandez, A; Celik, A; Dalchenko, M; De Mattia, M; Delgado, A; Dildick, S; Eusebi, R; Gilmore, J; Huang, T; Kamon, T; Mueller, R; Pakhotin, Y; Patel, R; Perloff, A; Perniè, L; Rathjens, D; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Damgov, J; De Guio, F; Dudero, P R; Faulkner, J; Gurpinar, E; Kunori, S; Lamichhane, K; Lee, S W; Libeiro, T; Mengke, T; Muthumuni, S; Peltola, T; Undleeb, S; Volobouev, I; Wang, Z; Greene, S; Gurrola, A; Janjam, R; Johns, W; Maguire, C; Melo, A; Ni, H; Padeken, K; Sheldon, P; Tuo, S; Velkovska, J; Xu, Q; Arenton, M W; Barria, P; Cox, B; Hirosky, R; Joyce, M; Ledovskoy, A; Li, H; Neu, C; Sinthuprasith, T; Wang, Y; Wolfe, E; Xia, F; Harr, R; Karchin, P E; Poudyal, N; Sturdy, J; Thapa, P; Zaleski, S; Brodski, M; Buchanan, J; Caillol, C; Dasu, S; Dodd, L; Duric, S; Gomber, B; Grothe, M; Herndon, M; Hervé, A; Hussain, U; Klabbers, P; Lanaro, A; Levine, A; Long, K; Loveless, R; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

    2017-12-15

    The first observation of top quark production in proton-nucleus collisions is reported using proton-lead data collected by the CMS experiment at the CERN LHC at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=8.16  TeV. The measurement is performed using events with exactly one isolated electron or muon candidate and at least four jets. The data sample corresponds to an integrated luminosity of 174  nb^{-1}. The significance of the tt[over ¯] signal against the background-only hypothesis is above 5 standard deviations. The measured cross section is σ_{tt[over ¯]}=45±8  nb, consistent with predictions from perturbative quantum chromodynamics.

  7. Static negative capacitance of a ferroelectric nano-domain nucleus

    Science.gov (United States)

    Sluka, Tomas; Mokry, Pavel; Setter, Nava

    2017-10-01

    Miniaturization of conventional field effect transistors (FETs) approaches the fundamental limits beyond which opening and closing the transistor channel require higher gate voltage swing and cause higher power dissipation and heating. This problem could be eliminated by placing a ferroelectric layer between the FET gate electrode and the channel, which effectively amplifies the gate voltage. The original idea of using a bulk ferroelectric negative capacitor suffers however from irreversible multi-domain ferroelectric switching, which does not allow us to stabilize static negative capacitance, while a recent reversible solution with super-lattices may be difficult to integrate onto FET. Here, we introduce a solution which provides static negative capacitance from a nano-domain nucleus. Phase-field simulations confirm the robustness of this concept, the conveniently achievable small effective negative capacitance and the potentially high compatibility of such a negative nano-capacitor with FET technology.

  8. Synaptic Plasticity in the Nucleus Accumbens: Lessons Learned from Experience.

    Science.gov (United States)

    Turner, Brandon D; Kashima, Daniel T; Manz, Kevin M; Grueter, Carrie A; Grueter, Brad A

    2018-01-24

    Synaptic plasticity contributes to behavioral adaptations. As a key node in the reward pathway, the nucleus accumbens (NAc) is important for determining motivation-to-action outcomes. Across animal models of motivation including addiction, depression, anxiety, and hedonic feeding, selective recruitment of neuromodulatory signals and plasticity mechanisms have been a focus of physiologists and behaviorists alike. Experience-dependent plasticity mechanisms within the NAc vary depending on the distinct afferents and cell-types over time. A greater understanding of molecular mechanisms determining how these changes in synaptic strength track with behavioral adaptations will provide insight into the process of learning and memory along with identifying maladaptations underlying pathological behavior. Here, we summarize recent findings detailing how changes in NAc synaptic strength and mechanisms of plasticity manifest in various models of motivational disorders.

  9. Skewering the subthalamic nucleus via a parietal approach.

    Science.gov (United States)

    Zrinzo, Ludvic; Holl, Etienne M; Petersen, Erika A; Limousin, Patricia; Foltynie, Thomas; Hariz, Marwan I

    2011-01-01

    A frontal burr hole around the level of the coronal suture is the conventional entry point when performing subthalamic nucleus (STN) deep brain stimulation (DBS). However, alternative approaches may sometimes be necessary. We present a report of delayed hardware erosion through the scalp in the left frontal region after successful bilateral STN DBS for Parkinson's disease. The left STN was retargeted via a parietal entry point. Significant improvement in UPDRS motor score (59%) was obtained with bilateral stimulation 6 months after re-operation. The literature was examined for similar approaches and the rationale, risks and benefits of non-frontal entry points in functional neurosurgery were explored. Together with a brief review of STN anatomy, this report demonstrates that the parietal approach to the STN remains a viable option in addition to the more traditional frontal access. Copyright © 2011 S. Karger AG, Basel.

  10. The LHC as a Proton-Nucleus Collider

    CERN Document Server

    Carli, C

    2006-01-01

    Following its initial operation as a proton-proton (p-p) and heavy-ion (208Pb82+-208Pb82+) collider, the LHC is expected to operate as a p-Pb collider. Later it may collide protons with other lighter nuclei such as 40Ar18+ or 16O8+. We show how the existing proton and lead-ion injector chains may be efficiently operated in tandem to provide these hybrid collisions. The two-in-one magnet design of the LHC main rings imposes different revolution frequencies for the two beams in part of the magnetic cycle. We discuss and evaluate the consequences for beam dynamics and estimate the potential performance of the LHC as a proton-nucleus collider.

  11. Observation of top quark production in proton-nucleus collisions

    Energy Technology Data Exchange (ETDEWEB)

    Sirunyan, Albert M; et al.

    2017-09-21

    The first observation of top quark production in proton-nucleus collisions is reported using proton-lead data collected by the CMS experiment at the CERN LHC at a nucleon-nucleon center-of-mass energy of $\\sqrt{s_\\mathrm{NN}} =$ 8.16 TeV. The measurement is performed using events with exactly one isolated electron or muon and at least four jets. The data sample corresponds to an integrated luminosity of 174 nb$^{-1}$. The significance of the $\\mathrm{t}\\overline{\\mathrm{t}}$ signal against the background-only hypothesis is above five standard deviations. The measured cross section is $\\sigma_{\\mathrm{t}\\overline{\\mathrm{t}}} =$ 45$\\pm$8 nb, consistent with predictions from perturbative quantum chromodynamics.

  12. Input/output properties of the lateral vestibular nucleus

    Science.gov (United States)

    Boyle, R.; Bush, G.; Ehsanian, R.

    2004-01-01

    This article is a review of work in three species, squirrel monkey, cat, and rat studying the inputs and outputs from the lateral vestibular nucleus (LVN). Different electrophysiological shock paradigms were used to determine the synaptic inputs derived from thick to thin diameter vestibular nerve afferents. Angular and linear mechanical stimulations were used to activate and study the combined and individual contribution of inner ear organs and neck afferents. The spatio-temporal properties of LVN neurons in the decerebrated rat were studied in response to dynamic acceleration inputs using sinusoidal linear translation in the horizontal head plane. Outputs were evaluated using antidromic identification techniques and identified LVN neurons were intracellularly injected with biocytin and their morphology studied.

  13. In-beam spectroscopic studies of the 44S nucleus

    Science.gov (United States)

    Cáceres, L.; Sohler, D.; Grévy, S.; Sorlin, O.; Dombrádi, Zs.; Bastin, B.; Achouri, N. L.; Angélique, J. C.; Azaiez, F.; Baiborodin, D.; Borcea, R.; Bourgeois, C.; Buta, A.; Bürger, A.; Chapman, R.; Dalouzy, J. C.; Dlouhy, Z.; Drouard, A.; Elekes, Z.; Franchoo, S.; Gaudefroy, L.; Iacob, S.; Laurent, B.; Lazar, M.; Liang, X.; Liénard, E.; Mrazek, J.; Nalpas, L.; Negoita, F.; Nowacki, F.; Orr, N. A.; Penionzhkevich, Y.; Podolyák, Zs.; Pougheon, F.; Poves, A.; Roussel-Chomaz, P.; Saint-Laurent, M. G.; Stanoiu, M.; Stefan, I.

    2012-02-01

    The structure of the 44S nucleus has been studied at GANIL through the one proton knock-out reaction from a 45Cl secondary beam at 42 A·MeV. The γ rays following the de-excitation of 44S were detected in flight using the 70 BaF2 detectors of the Château de Cristal array. An exhaustive γγ-coincidence analysis allowed an unambiguous construction of the level scheme up to an excitation energy of 3301 keV. The existence of the spherical 22+ state is confirmed and three new γ-ray transitions connecting the prolate deformed 21+ level were observed. Comparison of the experimental results to shell model calculations further supports a prolate and spherical shape coexistence with a large mixing of states built on the ground state band in 44S.

  14. Reward and reinforcement activity in the nucleus accumbens during learning

    Directory of Open Access Journals (Sweden)

    John Thomas Gale

    2014-04-01

    Full Text Available The nucleus accumbens core (NAcc has been implicated in learning associations between sensory cues and profitable motor responses. However, the precise mechanisms that underlie these functions remain unclear. We recorded single-neuron activity from the NAcc of primates trained to perform a visual-motor associative learning task. During learning, we found two distinct classes of NAcc neurons. The first class demonstrated progressive increases in firing rates at the go-cue, feedback/tone and reward epochs of the task, as novel associations were learned. This suggests that these neurons may play a role in the exploitation of rewarding behaviors. In contrast, the second class exhibited attenuated firing rates, but only at the reward epoch of the task. These findings suggest that some NAcc neurons play a role in reward-based reinforcement during learning.

  15. Nuclear receptors outside the nucleus: extranuclear signalling by steroid receptors

    Science.gov (United States)

    Levin, Ellis R.; Hammes, Stephen R.

    2017-01-01

    Steroid hormone receptors mediate numerous crucial biological processes and are classically thought to function as transcriptional regulators in the nucleus. However, it has been known for more than 50 years that steroids evoke rapid responses in many organs that cannot be explained by gene regulation. Mounting evidence indicates that most steroid receptors in fact exist in extranuclear cellular pools, including at the plasma membrane. This latter pool, when engaged by a steroid ligand, rapidly activates signals that affect various aspects of cellular biology. Research into the mechanisms of signalling instigated by extranuclear steroid receptor pools and how this extranuclear signalling is integrated with responses elicited by nuclear receptor pools provides novel understanding of steroid hormone signalling and its roles in health and disease. PMID:27729652

  16. One-pion production in neutrino-nucleus collisions

    Energy Technology Data Exchange (ETDEWEB)

    Hernández, E. [Departamento de Física Fundamental e IUFFyM, Universidad de Salamanca, E-37008 Salamanca (Spain); Nieves, J. [Instituto de Física Corpuscular (IFIC), Centro Mixto CSIC-Universidad de Valencia, Institutos de Investigación de Paterna, Apartado 22085, E-46071 Valencia (Spain); Vicente-Vacas, J. M. [Departamento de Física Teórica e IFIC, Centro Mixto Universidad de Valencia-CSIC, Institutos de Investigación de Paterna, Apartado 22085, E-46071 Valencia (Spain)

    2015-05-15

    We use our model for neutrino pion production on the nucleon to study pion production on a nucleus. The model is conveniently modified to include in-medium corrections and its validity is extended up to 2 GeV neutrino energies by the inclusion of new resonant contributions in the production process. Our results are compared with recent MiniBooNE data measured in mineral oil. Our total cross sections are below data for neutrino energies above ≈ 1 GeV. As with other theoretical calculations, the agreement with data improves if we neglect pion final state interaction. This is also the case for differential cross sections convoluted over the neutrino flux.

  17. Role of the nucleus in apoptosis: signaling and execution.

    Science.gov (United States)

    Prokhorova, Evgeniia A; Zamaraev, Alexey V; Kopeina, Gelina S; Zhivotovsky, Boris; Lavrik, Inna N

    2015-12-01

    Since their establishment in the early 1970s, the nuclear changes upon apoptosis induction, such as the condensation of chromatin, disassembly of nuclear scaffold proteins and degradation of DNA, were, and still are, considered as the essential steps and hallmarks of apoptosis. These are the characteristics of the execution phase of apoptotic cell death. In addition, accumulating data clearly show that some nuclear events can lead to the induction of apoptosis. In particular, if DNA lesions resulting from deregulation during the cell cycle or DNA damage induced by chemotherapeutic drugs or viral infection cannot be efficiently eliminated, apoptotic mechanisms, which enable cellular transformation to be avoided, are activated in the nucleus. The functional heterogeneity of the nuclear organization allows the tight regulation of these signaling events that involve the movement of various nuclear proteins to other intracellular compartments (and vice versa) to initiate and govern apoptosis. Here, we discuss how these events are coordinated to execute apoptotic cell death.

  18. The dolphin cochlear nucleus: topography, histology and functional implications.

    Science.gov (United States)

    Malkemper, E P; Oelschläger, H H A; Huggenberger, S

    2012-02-01

    Despite the outstanding auditory capabilities of dolphins, there is only limited information available on the cytology of the auditory brain stem nuclei in these animals. Here, we investigated the cochlear nuclei (CN) of five brains of common dolphins (Delphinus delphis) and La Plata dolphins (Pontoporia blainvillei) using cell and fiber stain microslide series representing the three main anatomical planes. In general, the CN in dolphins comprise the same set of subnuclei as in other mammals. However, the volume ratio of the dorsal cochlear nucleus (DCN) in relation to the ventral cochlear nucleus (VCN) of dolphins represents a minimum among the mammals examined so far. Because, for example, in cats the DCN is necessary for reflexive orientation of the head and pinnae towards a sound source, the massive restrictions in head movability in dolphins and the absence of outer ears may be correlated with the reduction of the DCN. Moreover, the same set of main neuron types were found in the dolphin CN as in other mammals, including octopus and multipolar cells. Because the latter two types of neurons are thought to be involved in the recognition of complex sounds, including speech, we suggest that, in dolphins, they may be involved in the processing of their communication signals. Comparison of the toothed whale species studied here revealed that large spherical cells were present in the La Plata dolphin but absent in the common dolphin. These neurons are known to be engaged in the processing of low-frequency sounds in terrestrial mammals. Accordingly, in the common dolphin, the absence of large spherical cells seems to be correlated with a shift of its auditory spectrum into the high-frequency range above 20 kHz. The existence of large spherical cells in the VCN of the La Plata dolphin, however, is enigmatic asthis species uses frequencies around 130 kHz. Copyright © 2011 Wiley Periodicals, Inc.

  19. Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons.

    Directory of Open Access Journals (Sweden)

    Miloslav eKolaj

    2014-04-01

    Full Text Available Neurons in the midline and intralaminar thalamic nuclei are components of an interconnected brainstem, limbic and prefrontal cortex neural network that is engaged during arousal, vigilance, motivated and addictive behaviors, and stress. To better understand the cellular mechanisms underlying these functions, here we review some of the recently characterized electrophysiological and neuropharmacological properties of neurons in the paraventricular thalamic nucleus (PVT, derived from whole cell patch clamp recordings in acute rat brain slice preparations. PVT neurons display firing patterns and ionic conductances (IT and IH that exhibit significant diurnal change. Their resting membrane potential is maintained by various ionic conductances that include inward rectifier (Kir, hyperpolarization-activated nonselective cation (HCN and TWIK-related acid sensitive (TASK K+ channels. Firing patterns are regulated by high voltage-activated (HVA and low voltage-activated (LVA Ca2+ conductances. Moreover, transient receptor potential (TRP-like nonselective cation channels together with Ca2+- and Na+-activated K+ conductances (KCa; KNa contribute to unique slow afterhyperpolarizing potentials (sAHPs that are generally not detectable in lateral thalamic or reticular thalamic nucleus neurons. We also report on receptor-mediated actions of GABA, glutamate, monoamines and several neuropeptides: arginine vasopressin, gastrin-releasing peptide, thyrotropin releasing hormone and the orexins (hypocretins. This review represents an initial survey of intrinsic and transmitter-sensitive ionic conductances that are deemed to be unique to this population of midline thalamic neurons, information that is fundamental to an appreciation of the role these thalamic neurons may play in normal central nervous system (CNS physiology and in CNS disorders that involve the dorsomedial thalamus.

  20. Subthalamic nucleus electrical stimulation modulates calcium activity of nigral astrocytes.

    Directory of Open Access Journals (Sweden)

    Elodie Barat

    Full Text Available BACKGROUND: The substantia nigra pars reticulata (SNr is a major output nucleus of the basal ganglia, delivering inhibitory efferents to the relay nuclei of the thalamus. Pathological hyperactivity of SNr neurons is known to be responsible for some motor disorders e.g. in Parkinson's disease. One way to restore this pathological activity is to electrically stimulate one of the SNr input, the excitatory subthalamic nucleus (STN, which has emerged as an effective treatment for parkinsonian patients. The neuronal network and signal processing of the basal ganglia are well known but, paradoxically, the role of astrocytes in the regulation of SNr activity has never been studied. PRINCIPAL FINDINGS: In this work, we developed a rat brain slice model to study the influence of spontaneous and induced excitability of afferent nuclei on SNr astrocytes calcium activity. Astrocytes represent the main cellular population in the SNr and display spontaneous calcium activities in basal conditions. Half of this activity is autonomous (i.e. independent of synaptic activity while the other half is dependent on spontaneous glutamate and GABA release, probably controlled by the pace-maker activity of the pallido-nigral and subthalamo-nigral loops. Modification of the activity of the loops by STN electrical stimulation disrupted this astrocytic calcium excitability through an increase of glutamate and GABA releases. Astrocytic AMPA, mGlu and GABA(A receptors were involved in this effect. SIGNIFICANCE: Astrocytes are now viewed as active components of neural networks but their role depends on the brain structure concerned. In the SNr, evoked activity prevails and autonomous calcium activity is lower than in the cortex or hippocampus. Our data therefore reflect a specific role of SNr astrocytes in sensing the STN-GPe-SNr loops activity and suggest that SNr astrocytes could potentially feedback on SNr neuronal activity. These findings have major implications given the

  1. GABAergic projections to the oculomotor nucleus in the goldfish (Carassius auratus

    Directory of Open Access Journals (Sweden)

    M. Angeles eLuque

    2011-02-01

    Full Text Available The mammalian oculomotor nucleus receives a strong -aminobutyric acid (GABAergic synaptic input, whereas such projections have rarely been reported in fish. In order to determine whether this synaptic organization is preserved across vertebrates, we investigated the GABAergic projections to the oculomotor nucleus in the goldfish by combining retrograde transport of biotin dextran amine, injected into the antidromically identified oculomotor nucleus, and GABA immunohistochemistry. The main source of GABAergic afferents to the oculomotor nucleus was the ipsilateral anterior octaval nucleus, with only a few, if any, GABAergic neurons being located in the contralateral tangential and descending nuclei of the octaval column. In mammals there is a nearly exclusive ipsilateral projection from vestibular neurons to the oculomotor nucleus via GABAergic inhibitory inputs; thus, the vestibulooculomotor GABAergic circuitry follows a plan that appears to be shared throughout the vertebrate phylogeny. The second major source of GABAergic projections was the rhombencephalic reticular formation, primarily from the medial area but, to a lesser extent, from the inferior area. A few GABAergic oculomotor projecting neurons were also observed in the ipsilateral nucleus of the medial longitudinal fasciculus. The GABAergic projections from neurons located in both the reticular formation surrounding the abducens nucleus and the nucleus of the medial reticular formation have primarily been related to the control of saccadic eye movements. Finally, all retrogradely labeled internuclear neurons of the abducens nucleus, and neurons in the cerebellum (close to the caudal lobe, were negative for GABA. These data suggest that the vestibuloocular and saccadic inhibitory GABAergic systems appear early in vertebrate phylogeny to modulate the firing properties of the oculomotor nucleus motoneurons.

  2. Corticotropin-releasing factor within the central nucleus of the amygdala and the nucleus accumbens shell mediates the negative affective state of nicotine withdrawal in rats

    OpenAIRE

    Marcinkiewcz, Catherine A.; Prado, Melissa M.; Isaac, Shani K.; Marshall, Alex.; Rylkova, Daria; Bruijnzeel, Adrie W.

    2009-01-01

    Tobacco addiction is a chronic disorder that is characterized by a negative affective state upon smoking cessation and relapse after periods of abstinence. Previous research has shown that an increased central release of corticotropin-releasing factor (CRF) at least partly mediates the deficit in brain reward function associated with nicotine withdrawal in rats. The aim of these studies was to investigate the role of CRF in the central nucleus of the amygdala (CeA), the lateral bed nucleus of...

  3. NPY and VGF Immunoreactivity Increased in the Arcuate Nucleus, but Decreased in the Nucleus of the Tractus Solitarius, of Type-II Diabetic Patients

    Science.gov (United States)

    Saderi, Nadia; Salgado-Delgado, Roberto; Avendaño-Pradel, Rafael; Basualdo, Maria del Carmen; Ferri, Gian-Luca; Chávez-Macías, Laura; Escobar, Carolina; Buijs, Ruud M.

    2012-01-01

    Ample animal studies demonstrate that neuropeptides NPY and α-MSH expressed in Arcuate Nucleus and Nucleus of the Tractus Solitarius, modulate glucose homeostasis and food intake. In contrast is the absence of data validating these observations for human disease. Here we compare the post mortem immunoreactivity of the metabolic neuropeptides NPY, αMSH and VGF in the infundibular nucleus, and brainstem of 11 type-2 diabetic and 11 non-diabetic individuals. α-MSH, NPY and tyrosine hydroxylase in human brain are localized in the same areas as in rodent brain. The similar distribution of NPY, α-MSH and VGF indicated that these neurons in the human brain may share similar functionality as in the rodent brain. The number of NPY and VGF immuno positive cells was increased in the infundibular nucleus of diabetic subjects in comparison to non-diabetic controls. In contrast, NPY and VGF were down regulated in the Nucleus of the Tractus Solitarius of diabetic patients. These results suggest an activation of NPY producing neurons in the arcuate nucleus, which, according to animal experimental studies, is related to a catabolic state and might be the basis for increased hepatic glucose production in type-2 diabetes. PMID:22808091

  4. Input-output organization of inhibitory neurons in the interstitial nucleus of Cajal projecting to the contralateral trochlear and oculomotor nucleus.

    Science.gov (United States)

    Sugiuchi, Y; Takahashi, M; Shinoda, Y

    2013-08-01

    Neurons in the interstitial nucleus of Cajal (INC) that are known to be involved in eye and head movements are excitatory. We investigated the input-output organization of inhibitory INC neurons involved in controlling vertical saccades. Intracellular recordings were made in INC neurons activated antidromically by stimulation of the contralateral trochlear or oculomotor nucleus, and their synaptic input properties from the superior colliculi (SCs) and the contralateral INC were analyzed in anesthetized cats. Many INC neurons projected to the contralateral trochlear nucleus, Forel's field H, INC, and oculomotor nucleus, and mainly received monosynaptic excitation followed by disynaptic inhibition from the ipsi- and contralateral SCs. After sectioning the commissural connections between the SCs, these neurons received monosynaptic excitation from the ipsilateral medial SC and disynaptic inhibition via the INC from the contralateral lateral SC. Another group of INC neurons were antidromically activated from the contralateral oculomotor nucleus, INC and Forel's field H, but not from the trochlear nucleus, and received monosynaptic excitation from the ipsilateral lateral SC and disynaptic inhibition from the contralateral medial SC. The former group was considered to inhibit contralateral trochlear and inferior rectus motoneurons in upward saccades, whereas the latter was considered to inhibit contralateral superior rectus and inferior oblique motoneurons in downward saccades. The mutual inhibition existed between these two groups of INC neurons for upward saccades on one side and downward saccades on the other. This pattern of input-output organization of inhibitory INC neurons suggests that the basic neural circuits for horizontal and vertical saccades are similar.

  5. Redistribution of particles across the nucleus of comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Thomas, N.; Davidsson, B.; El-Maarry, M. R.; Fornasier, S.; Giacomini, L.; Gracia-Berná, A. G.; Hviid, S. F.; Ip, W.-H.; Jorda, L.; Keller, H. U.; Knollenberg, J.; Kührt, E.; La Forgia, F.; Lai, I. L.; Liao, Y.; Marschall, R.; Massironi, M.; Mottola, S.; Pajola, M.; Poch, O.; Pommerol, A.; Preusker, F.; Scholten, F.; Su, C. C.; Wu, J. S.; Vincent, J.-B.; Sierks, H.; Barbieri, C.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Rickman, H.; A'Hearn, M. F.; Barucci, M. A.; Bertaux, J.-L.; Bertini, I.; Cremonese, G.; Da Deppo, V.; Debei, S.; de Cecco, M.; Fulle, M.; Groussin, O.; Gutierrez, P. J.; Kramm, J.-R.; Küppers, M.; Lara, L. M.; Lazzarin, M.; Lopez Moreno, J. J.; Marzari, F.; Michalik, H.; Naletto, G.; Agarwal, J.; Güttler, C.; Oklay, N.; Tubiana, C.

    2015-11-01

    Context. We present an investigation of the surface properties of areas on the nucleus of comet 67P/Churyumov-Gerasimenko. Aims: We aim to show that transport of material from one part of the cometary nucleus to another is a significant mechanism that influences the appearance of the nucleus and the surface thermal properties. Methods: We used data from the OSIRIS imaging system onboard the Rosetta spacecraft to identify surface features on the nucleus that can be produced by various transport mechanisms. We used simple calculations based on previous works to establish the plausibility of dust transport from one part of the nucleus to another. Results: We show by observation and modeling that "airfall" as a consequence of non-escaping large particles emitted from the neck region of the nucleus is a plausible explanation for the smooth thin deposits in the northern hemisphere of the nucleus. The consequences are also discussed. We also present observations of aeolian ripples and ventifacts. We show by numerical modeling that a type of saltation is plausible even under the rarified gas densities seen at the surface of the nucleus. However, interparticle cohesive forces present difficulties for this model, and an alternative mechanism for the initiation of reptation and creep may result from the airfall mechanism. The requirements on gas density and other parameters of this alternative make it a more attractive explanation for the observations. The uncertainties and implications are discussed.

  6. Prospects for measuring coherent neutrino-nucleus elastic scattering at a stopped-pion neutrino source

    OpenAIRE

    Scholberg, Kate

    2005-01-01

    Rates of coherent neutrino-nucleus elastic scattering at a high-intensity stopped-pion neutrino source in various detector materials (relevant for novel low-threshold detectors) are calculated. Sensitivity of a coherent neutrino-nucleus elastic scattering experiment to new physics is also explored.

  7. The performance of a hydrogel nucleus pulposus prosthesis in an ex vivo canine model

    NARCIS (Netherlands)

    Bergknut, N.; Smolders, L.A.; Koole, L.H.; Voorhout, G.; Hagman, R.E.; Lagerstedt, A.S.; Saralidze, K.; Hazewinkel, H.A.W.; van der Veen, A.J.; Meij, B.P.

    2010-01-01

    A nucleus pulposus prosthesis (NPP) made of the hydrogel N-vinyl-2-pyrrolidinone copolymerized with 2-(4'-iodobenzoyl)-oxo-ethyl methacrylate has recently been developed. The special features of this NPP, i.e. intrinsic radiopacity and its ability to swell in situ to fill the nucleus cavity and

  8. Rotational structures in the odd-odd nucleus {sup 80}Y

    Energy Technology Data Exchange (ETDEWEB)

    Bucurescu, D. [Institutul de Fizica Atomica, Bucharest (Romania); Ur, C.A. [Institutul de Fizica Atomica, Bucharest (Romania); Bazzacco, D. [Istituto Nazionale di Fisica Nucleare, Padua (Italy)]|[Padua Univ. (Italy). Dipt. di Fisica; Rossi-Alvarez, C. [Istituto Nazionale di Fisica Nucleare, Padua (Italy)]|[Padua Univ. (Italy). Dipt. di Fisica; Spolaore, P. [Istituto Nazionale di Fisica Nucleare, Legnaro (Italy). Lab. Nazionali di Legnaro; Petrache, C.M. [Istituto Nazionale di Fisica Nucleare, Padua (Italy)]|[Padua Univ. (Italy). Dipt. di Fisica; Ionescu-Bujor, M. [Institutul de Fizica Atomica, Bucharest (Romania); Lunardi, S. [Istituto Nazionale di Fisica Nucleare, Padua (Italy)]|[Padua Univ. (Italy). Dipt. di Fisica; Medina, N.H. [Istituto Nazionale di Fisica Nucleare, Padua (Italy)]|[Padua Univ. (Italy). Dipt. di Fisica; Napoli, D.R. [Istituto Nazionale di Fisica Nucleare, Legnaro (Italy). Lab. Nazionali di Legnaro; De Poli, M. [Istituto Nazionale di Fisica Nucleare, Legnaro (Italy). Lab. Nazionali di Legnaro; De Angelis, G. [Istituto Nazionale di Fisica Nucleare, Legnaro (Italy). Lab. Nazionali di Legnaro; Brandolini, F. [Istituto Nazionale di Fisica Nucleare, Padua (Italy)]|[Padua Univ. (Italy). Dipt. di Fisica; Gadea, A. [Istituto Nazionale di Fisica Nucleare, Legnaro (Italy). Lab. Nazionali di Legnaro; Pavan, P. [Istituto Nazionale di Fisica Nucleare, Legnaro (Italy). Lab. Nazionali di Legnaro; Segato, G.F. [Istituto Nazionale di Fisica Nucleare, Padua (Italy)]|[Padua Univ. (Italy). Dipt. di Fisica

    1995-09-01

    High spin states have been observed for the first time in the odd-odd nucleus {sup 80}Y, by using the {sup 24}Mg({sup 58}Ni,pn) reaction at 180 MeV. Eight rotational bands have been established, indicating a nucleus with appreciable deformation. (orig.)

  9. Methods for the mineralogical and textural analysis of comet nucleus samples

    Science.gov (United States)

    Stoeffler, D.; Dueren, H.; Knoelker, J.

    1989-01-01

    The objectives and instrumental requirements of a petrographic analysis of porous comet nucleus material are reviewed. Assumptions about its composition and texture, and the available techniques for the microscopic analysis of comet analogue material are investigated. New techniques required for the petrographic investigation of natural and artificial comet nucleus samples are also considered.

  10. Dopamine efflux in nucleus accumbens shell and core in response to appetitive classical conditioning

    NARCIS (Netherlands)

    Cheng, J. J.; de Bruin, J. P. C.; Feenstra, M. G. P.

    2003-01-01

    Dopamine transmission within the nucleus accumbens has been implicated in associative reinforcement learning. We investigated the effect of appetitive classical conditioning on dopamine efflux in the rat nucleus accumbens shell and core, as dopamine may be differentially activated by conditioned and

  11. Three-Dimensional Organization of Chromosome Territories in the Human Interphase Nucleus

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); J. Langowski (Jörg)

    1999-01-01

    textabstractDespite the successful linear sequencing of the human genome its three-dimensional structure is widely unknown. The regulation of genes has been shown to be connected closely to the three-dimensional organization of the genome in the cell nucleus. The nucleus of the cell has for a long

  12. The Stimulatory Effect of Notochordal Cell-Conditioned Medium in a Nucleus Pulposus Explant Culture

    NARCIS (Netherlands)

    de Vries, Stefan A H; van Doeselaar, Marina; Meij, Björn P; Tryfonidou, Marianna A; Ito, K|info:eu-repo/dai/nl/345809610

    2016-01-01

    Objectives: Notochordal cell-conditioned medium (NCCM) has previously shown to have a stimulatory effect on nucleus pulposus cells (NPCs) and bone marrow stromal cells (BMSCs) in alginate and pellet cultures. These culture methods provide a different environment than the nucleus pulposus (NP)

  13. The Stimulatory Effect of Notochordal-Cell Conditioned Medium in a Nucleus Pulposus Explant Culture

    NARCIS (Netherlands)

    de Vries, Stefan; Doeselaar, Marina van; Meij, Björn; Tryfonidou, M; Ito, Keita

    2015-01-01

    OBJECTIVES: Notochordal cell-conditioned medium (NCCM) has previously shown to have a stimulatory effect on nucleus pulposus cells (NPCs) and bone marrow stromal cells (BMSCs) in alginate and pellet cultures. These culture methods provide a different environment than the nucleus pulposus (NP)

  14. Whisker movements evoked by stimulation of single motor neurons in the facial nucleus of the rat

    NARCIS (Netherlands)

    L.J. Herfst (Lucas); M. Brecht (Michael)

    2008-01-01

    textabstractThe lateral facial nucleus is the sole output structure whose neuronal activity leads to whisker movements. To understand how single facial nucleus neurons contribute to whisker movement we combined single-cell stimulation and high-precision whisker tracking. Half of the 44 stimulated

  15. Shape study of the N=Z waiting-point nucleus 72Kr via beta decay

    CERN Document Server

    Briz Monago, Jose Antonio; Nácher González, Enrique

    The Ph.D. thesis entitled “Shape study of the N=Z waiting-point nucleus 72Kr via beta decay” is devoted to the study of the shape of the ground state of the 72Kr nucleus. It is an N=Z nucleus in the mass region A~70-80 where shape transitions and the shape coexistence phenomena have been identified. Furthermore, this nucleus participates in the rp-process as a waiting point due to the slowdown of the process taking place at the arrival to this nucleus. The study of the properties of this nucleus is interesting from the Nuclear Structure point of view, for the phenomena occurring in its mass region and have been predicted for it, and from the Nuclear Astrophysics for the accurate performance of astrophysical calculations. The β+/EC decay of the 72Kr nucleus has been studied through two complementary experiments at the ISOLDE facility at CERN in Geneva (Switzerland). In one of them, the low-spin structure of the daughter nucleus, 72Br, has been revised via conversion electron spectroscopy where the convers...

  16. Non-compound nucleus fission in actinide and pre-actinide regions

    Indian Academy of Sciences (India)

    fragment angular distribution in 28Si+176Yb reaction did not show a large contribution from the non-compound nucleus fission. Data on the evaporation residue cross-sections, in addition to those on mass and angular distributions, are necessary for better understanding of the contribution from non-compound nucleus ...

  17. Protein Kinase C Epsilon Activity in the Nucleus Accumbens and Central Nucleus of the Amygdala Mediates Binge Alcohol Consumption.

    Science.gov (United States)

    Cozzoli, Debra K; Courson, Justin; Rostock, Charlotte; Campbell, Rianne R; Wroten, Melissa G; McGregor, Hadley; Caruana, Amanda L; Miller, Bailey W; Hu, Jia-Hua; Wu Zhang, Ping; Xiao, Bo; Worley, Paul F; Crabbe, John C; Finn, Deborah A; Szumlinski, Karen K

    2016-03-15

    Protein kinase C epsilon (PKCε) is emerging as a potential target for the development of pharmacotherapies to treat alcohol use disorders, yet little is known regarding how a history of a highly prevalent form of drinking, binge alcohol intake, influences enzyme priming or the functional relevance of kinase activity for excessive alcohol intake. Immunoblotting was employed on tissue from subregions of the nucleus accumbens (NAc) and the amygdala to examine both idiopathic and binge drinking-induced changes in constitutive PKCε priming. The functional relevance of PKCε translocation for binge drinking and determination of potential upstream signaling pathways involved were investigated using neuropharmacologic approaches within the context of two distinct binge drinking procedures, drinking in the dark and scheduled high alcohol consumption. Binge alcohol drinking elevated p(Ser729)-PKCε levels in both the NAc and the central nucleus of the amygdala (CeA). Moreover, immunoblotting studies of selectively bred and transgenic mouse lines revealed a positive correlation between the propensity to binge drink alcohol and constitutive p(Ser729)-PKCε levels in the NAc and CeA. Finally, neuropharmacologic inhibition of PKCε translocation within both regions reduced binge alcohol consumption in a manner requiring intact group 1 metabotropic glutamate receptors, Homer2, phospholipase C, and/or phosphotidylinositide-3 kinase function. Taken together, these data indicate that PKCε signaling in both the NAc and CeA is a major contributor to binge alcohol drinking and to the genetic propensity to consume excessive amounts of alcohol. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Separable Representation of Nucleon-Nucleus Optical Potentials as Input to (d; p) Reaction Calculations

    Science.gov (United States)

    Hlophe, Linda D.

    The three-body description of deuteron-induced nuclear reactions requires the nucleon-nucleon (NN) and effective nucleon-nucleus interactions as input. The latter are given by Optical Model Potentials (OMPs), which are complex as well as energy-dependent. While a lot of effort has been dedicated to creating separable NN potentials, the same is not true for the nucleon-nucleus OMPs. In this work, separable representations of nucleon-nucleus OMPs are presented. To construct separable representations of neutron-nucleus OMPs, a scheme due to Ernst, Shakin, and Thaler (EST) is adopted as a starting point. It is shown that, by including both incoming and outgoing scattering states in the EST scheme, separable expansions for complex neutron-nucleus potentials that partially obey reciprocity are obtained. For the application to neutron-nucleus potentials that are complex as well as energy-dependent, a further generalization is carried out leading to an energy-dependent separable expansion that exactly fulfills reciprocity. By working exclusively with half-shell transition matrices in momentum space, the implementation of these separable representation schemes is straightforward. The proton-nucleus interaction consists of a short-ranged nuclear piece as well as the long-ranged point-Coulomb potential. After separating the point-Coulomb piece via the Gell-Mann-Goldberger relation, one is left with the short-ranged potential in the Coulomb basis. An extension of the separable representation schemes for neutron-nucleus OMPs to proton-nucleus systems thus requires scattering solutions in the Coulomb basis. This complicates a momentum space implementation of the aforementioned separable expansions. However, by employing the techniques first suggested by Elster, Liu, and Thaler, the separable representation schemes generalized for proton-nucleus OMPs are implemented in a similar manner to neutron-nucleus OMPs. Taking into account the internal structure of the nucleus leads to

  19. Neurotransmitter mechanisms in the nucleus accumbens septi and related regions in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I.

    1981-06-30

    The investigation compares the localization of different transmitter candidates, particularly the amino acide ..gamma..-aminobutyrate (GABA) and glutamate (GLU), in limbic and basal ganglia regions in the rat brain. In particular, the characteristics of nucleus accumbens septi have been studied in some detail. GABA neurons have been found in nucleus accumbens, and GABA projections from this nucleus have been identified in restricted basal forebrain and mesencephalic regions. GLU projections from the neo- or allocortex have been found to terminate in nucleus accumbens and other forebrain and hypothalamic nuclei. Neurotransmitters in local neurons have been identified in the hippocampus, nucleus accumbens, septum and caudatoputamen by means of local kainic acid injections, while neurons in the mediobasal hypothalamus have been studied after systemic treatment of newborn animals with monosodium glutamate. The results are discussed as a basis for a better understanding of limbic-basal ganglia interactions.

  20. Projection of secondary vestibular neurons to the abducens nucleus in the carpet shark Cephaloscyllium isabella.

    Science.gov (United States)

    Montgomery, J C; Cotton, P

    1985-01-01

    The abducens nucleus in carpet sharks is not a discrete delimited nucleus, as the dendrites of the motoneurons extend into the reticular formation and the medial longitudinal fasciculus. Injections of horseradish peroxidase (HRP) designed to trace the inputs to these neurons are therefore difficult to confine to this system alone. Despite this problem a consistent finding from injection of HRP in the area of the abducens nucleus is the retrograde labelling of a column of cells in the contralateral octaval nuclei. The column of cells is predominantly in the ventral portion of the descending octaval nucleus, but does straddle the entrance of nerve VIII, extending into the caudal part of the ascending octaval nucleus. Labelled cells correspond in location and morphology to those cells receiving input from horizontal canal afferent fibers, confirming the trineuronal nature of the horizontal vestibulo-ocular reflex arc in elasmobranch fishes.

  1. Preservation of the nucleus X-pelvic floor motosystem in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Schrøder, H D; Reske-Nielsen, E

    1984-01-01

    were observed in Onuf's nucleus X, not even in 8 cases in which other caudal motoneuron nuclei presented a severe loss of neurons. The striated sphincters proper demonstrated no signs of neurogenic atrophy in contrast to muscles in the limbs. The bulbo- and ischiocavernosus muscles, also supposedly......Fourteen cases of amyotrophic lateral sclerosis (ALS) were investigated neuropathologically, emphazising the sacral spinal cord which contains Onuf's nucleus X. The nucleus innervates the pelvic sphincters. In two cases, small striated pelvic muscles were studied. No changes characteristic of ALS...... innervated by Onuf's nucleus, were without pathological changes. Moreover, the latter two muscles were found to have a composition very similar to that of the sphincters. This indicates that a characteristic morphology of the nucleus X-innervated muscles exists. A review of the clinical records of all...

  2. Influence of recipient cytoplasm cell stage on transcription in bovine nucleus transfer embryos

    DEFF Research Database (Denmark)

    Smith, Steven D.; Soloy, Eva; Kanka, Jiri

    1996-01-01

    Nucleus transfer for the production of multiple embryos derived from a donor embryo relies upon the reprogramming of the donor nucleus so that it behaves similar to a zygotic nucleus. One indication of nucleus reprogramming is the RNA synthetic activity. In normal bovine embryogenesis, the embryo...... relies upon maternally derived RNA transcripts up to the 8-cell stage, at which time it begins to transcribe its own RNA. In this experiment, RNA synthesis was detected in nucleus transfer embryos (NTE) and control embryos by pulsing with 3H-uridine, fixation, and autoradiography on semithin sections....... NTE were produced using either a MII phase (nonactivated) cytoplasts at 32 hr of maturation or S-phase (activated) cytoplasts activated with calcium ionophore A23187 and cycloheximide treatment approximately 8 hr prior to fusion with a blastomere from an in-vitro-produced morula stage embryo at 32 hr...

  3. Finite Element Study of a Lumbar Intervertebral Disc Nucleus Replacement Device.

    Science.gov (United States)

    Coogan, Jessica S; Francis, W Loren; Eliason, Travis D; Bredbenner, Todd L; Stemper, Brian D; Yoganandan, Narayan; Pintar, Frank A; Nicolella, Daniel P

    2016-01-01

    Nucleus replacement technologies are a minimally invasive alternative to spinal fusion and total disc replacement that have the potential to reduce pain and restore motion for patients with degenerative disc disease. Finite element modeling can be used to determine the biomechanics associated with nucleus replacement technologies. The current study focuses on a new nucleus replacement device designed as a conforming silicone implant with an internal void. A validated finite element model of the human lumbar L3-L4 motion segment was developed and used to investigate the influence of the nucleus replacement device on spine biomechanics. In addition, the effect of device design changes on biomechanics was determined. A 3D, L3-L4 finite element model was constructed from medical imaging data. Models were created with the normal intact nucleus, the nucleus replacement device, and a solid silicone implant. Probabilistic analysis was performed on the normal model to provide quantitative validation metrics. Sensitivity analysis was performed on the silicone Shore A durometer of the device. Models were loaded under axial compression followed by flexion/extension, lateral bending, or axial rotation. Compressive displacement, endplate stresses, reaction moment, and annulus stresses were determined and compared between the different models. The novel nucleus replacement device resulted in similar compressive displacement, endplate stress, and annulus stress and slightly higher reaction moment compared with the normal nucleus. The solid implant resulted in decreased displacement, increased endplate stress, decreased annulus stress, and decreased reaction moment compared with the novel device. With increasing silicone durometer, compressive displacement decreased, endplate stress increased, reaction moment increased, and annulus stress decreased. Finite element analysis was used to show that the novel nucleus replacement device results in similar biomechanics compared with the

  4. Finite element study of a lumbar intervertebral disc nucleus replacement device

    Directory of Open Access Journals (Sweden)

    Jessica S Coogan

    2016-12-01

    Full Text Available Nucleus replacement technologies are a minimally invasive alternative to spinal fusion and total disc replacement that have the potential to reduce pain and restore motion for patients with degenerative disc disease. Finite element modeling can be used to determine the biomechanics associated with nucleus replacement technologies. The current study focuses on a new nucleus replacement device designed as a conforming silicone implant with an internal void. A validated finite element model of the human lumbar L3-L4 motion segment was developed and used to investigate the influence of the nucleus replacement device on spine biomechanics. In addition, the effect of device design changes on biomechanics was determined. A 3D, L3-L4 finite element model was constructed from medical imaging data. Models were created with the normal intact nucleus, the nucleus replacement device, and a solid silicone implant. Probabilistic analysis was performed on the normal model to provide quantitative validation metrics. Sensitivity analysis was performed on the silicone Shore A durometer of the device. Models were loaded under axial compression followed by flexion/extension, lateral bending, or axial rotation. Compressive displacement, endplate stresses, reaction moment, and annulus stresses were determined and compared between the different models. The novel nucleus replacement device resulted in similar compressive displacement, endplate stress, and annulus stress and slightly higher reaction moment compared with the normal nucleus. The solid implant resulted in decreased displacement, increased endplate stress, decreased annulus stress, and decreased reaction moment compared with the novel device. With increasing silicone durometer, compressive displacement decreased, endplate stress increased, reaction moment increased, and annulus stress decreased. Finite element analysis was used to show that the novel nucleus replacement device results in similar biomechanics

  5. EL NÚCLEO PEDUNCULOPONTINO Y SU RELACIÓN CON LA FISIOPATOLOGÍA DE LA ENFERMEDAD DE PARKINSON The Pedunculopontine Nucleus and its Relationship to the Pathophysiology of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    LISETTE BLANCO LEZCANO

    2012-12-01

    Full Text Available Varias décadas de investigaciones neuropatológicas e imagenológicas han proporcionado suficientes evidencias acerca de las alteraciones en la neurotransmisión colinérgica que acompañan a la disfunción dopaminérgica en la enfermedad de Parkinson (EP. El núcleo pedunculopontino tegmental laterodorsal (NPP representa una de las fuentes principales de proyecciones colinérgicas en el cerebro y a su vez es el origen de la única proyección colinérgica que recibe la substantia nigra pars compacta (SNpc. Actualmente el estudio de la participación del NPP en la fisiopatología de la EP toma en cuenta dos vertientes: el impacto de la pérdida temprana de la influencia excitatoria pontina sobre la SNpc asociado a la degeneración temprana del NPP y la estimulación a baja frecuencia del NPP como tratamiento quirúrgico beneficioso para los signos axiales de la EP. El NPP ha emergido como una estructura esencial en la comprensión de la fisiopatología de la EP dado sus relaciones con los núcleos de los ganglios basales, el tálamo, la corteza motora y la médula espinal. La degeneración de algunas de sus poblaciones neuronales en etapas presintomáticas de la EP ha sugerido una relación causa-efecto entre este hallazgo y la muerte de las células dopaminérgicas nigrales. Por otra parte la estimulación del NPP tiene resultados favorables sobre los trastornos posturales y de la marcha, los cuales se presentan en etapas tardías de la EP y son refractarios a otros tratamientos farmacológicos y quirúrgicos.Several decades of neuropathologic and imagenologic investigations have provided sufficient evidences about alterations in cholinergic neurotransmission that go together with the dopaminergic dysfunction in Parkinson s disease (PD. The laterodorsal tegmental pedunculopontine nucleus (PPN represents one of the main sources of cholinergic projections into the brain and at the same time the origin of the only cholinergic projection that

  6. Clinical study of intelligent phacoemulsification for hard nucleus cataract extraction

    Directory of Open Access Journals (Sweden)

    Cun Sun

    2016-07-01

    Full Text Available AIM: To compare the efficiency and safety of torsional phacoemulsification with or without intelligent phacoemulsification(IPsoftware in hard nucleus cataract extraction. METHODS: Ninety two eyes with Ⅳ-Ⅴgrades cataracts were enrolled in this randomized prospective study. Operated eyes were divided into two groups-those operated without IP software(non-IP group, n=43and those operated using IP software(IP group, n=49. The two groups were compared in terms of ultrasound time(USTand cumulative dissipated energy(CDE. Post-operative outcome measures included the corneal edema and best-corrected visual acuity(BCVAat 1,7d and 3mo postoperatively, corneal endothelial cell density and percentage of hexagonal cell at 7d and 3mo postoperatively. RESULTS: UST was measured as 52.51±9.64s in non-IP Group and 48.79±7.13s in IP Group(P=0.030. CDE was 15.78±3.73% in non-IP Group and 14.29±2.77% in IP Group(P=0.026. At the first postoperative day, the rate of BCVA>0.1 in non-IP Group was 56%, and the rate in IP Group was 79%(P=0.066. Corneal edema in non-IP Group was 2.98±0.77 scores, and in IP Group it was 2.61±0.64 scores(P=0.021. At the postoperative 7 and 30d, the BCVA and corneal edema were no differences between two groups. At the postoperative 7d, corneal endothelial cell density in non-IP Group were 2497.95±211.48/mm2, less than 2586.26±154.71/mm2 in IP Group(P=0.029; percentage of hexagonal cell in IP group was 48.33±8.69%,higher than 44.19±9.48% of non-IP group(P=0.030. CONCLUSION: In hard nucleus cataract extraction, the IP software can combine the advantages of the two kinds of ultrasonic modes, which is more effective with lower ultrasound energy and less injury for the corneal endothclium, and is helpful for the recovery of vision at early stage after surgeries.

  7. Geniculohypothalamic GABAergic projections gate suprachiasmatic nucleus responses to retinal input.

    Science.gov (United States)

    Hanna, Lydia; Walmsley, Lauren; Pienaar, Abigail; Howarth, Michael; Brown, Timothy M

    2017-06-01

    Visual input to the suprachiasmatic nucleus circadian clock is critical for animals to adapt their physiology and behaviour in line with the solar day. In addition to direct retinal projections, the clock receives input from the visual thalamus, although the role of this geniculohypothalamic pathway in circadian photoreception is poorly understood. In the present study, we develop a novel brain slice preparation that preserves the geniculohypothalamic pathway to show that GABAergic thalamic neurons inhibit retinally-driven activity in the central clock in a circadian time-dependent manner. We also show that in vivo manipulation of thalamic signalling adjusts specific features of the hypothalamic light response, indicating that the geniculohypothalamic pathway is primarily activated by crossed retinal inputs. Our data provide a mechanism by which geniculohypothalamic signals can adjust the magnitude of circadian and more acute hypothalamic light responses according to time-of-day and establish an important new model for future investigations of the circadian visual system. Sensory input to the master mammalian circadian clock, the suprachiasmatic nucleus (SCN), is vital in allowing animals to optimize physiology and behaviour alongside daily changes in the environment. Retinal inputs encoding changes in external illumination provide the principle source of such information. The SCN also receives input from other retinorecipient brain regions, primarily via the geniculohypothalamic tract (GHT), although the contribution of these indirect projections to circadian photoreception is currently poorly understood. To address this deficit, in the present study, we established an in vitro mouse brain slice preparation that retains connectivity across the extended circadian system. Using multi-electrode recordings, we first confirm that this preparation retains intact optic projections to the SCN, thalamus and pretectum and a functional GHT. We next show that optogenetic

  8. Decay Properties of the Halo Nucleus $^{11}$Li

    CERN Multimedia

    2002-01-01

    During the past years a considerable experimental effort has been devoted to the production and study of nuclei close to the neutron and proton drip-lines. The most spectacular phenomenon encountered is the occurrence of neutron halos in the loosely bound neutron rich nuclei. \\\\ \\\\ Another interesting feature, observed at ISOLDE, which most likely is connected to the halo structure, is the very strong (super-allowed) Gamow-Teller $\\beta$- transitions to highly excited states which are systematically observed for the lightest neutron rich drip-line nuclei. These transitions might be viewed as arising from the quasi-free $\\beta$ -decay of the halo neutrons. It is proposed to make a detailed study of the $\\beta$- strength function for $^{11}$Li, a nuclide having a half-life of 8.2 ms and a Q $\\beta$-value of 20.73~MeV. \\\\ \\\\ So far only a lower limit of the Gamow-Teller transition rate to highly excited states ($\\approx$~18.5~MeV) in the daughter nucleus has been obtained from measurements of $\\beta$-delayed tri...

  9. Shaping Chromatin in the Nucleus: The Bricks and the Architects.

    Science.gov (United States)

    Sitbon, David; Podsypanina, Katrina; Yadav, Tejas; Almouzni, Geneviève

    2017-12-05

    Chromatin organization in the nucleus provides a vast repertoire of information in addition to that encoded genetically. Understanding how this organization impacts genome stability and influences cell fate and tumorigenesis is an area of rapid progress. Considering the nucleosome, the fundamental unit of chromatin structure, the study of histone variants (the bricks) and their selective loading by histone chaperones (the architects) is particularly informative. Here, we report recent advances in understanding how relationships between histone variants and their chaperones contribute to tumorigenesis using cell lines and Xenopus development as model systems. In addition to their role in histone deposition, we also document interactions between histone chaperones and other chromatin factors that govern higher-order structure and control DNA metabolism. We highlight how a fine-tuned assembly line of bricks (H3.3 and CENP-A) and architects (HIRA, HJURP, and DAXX) is key in adaptation to developmental and pathological changes. An example of this conceptual advance is the exquisite sensitivity displayed by p53-null tumor cells to modulation of HJURP, the histone chaperone for CENP-A (CenH3 variant). We discuss how these findings open avenues for novel therapeutic paradigms in cancer care. © 2017 Sitbon et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Nicotinic modulation of serotonergic activity in the dorsal raphe nucleus.

    Science.gov (United States)

    Hernandez-Lopez, Salvador; Garduño, Julieta; Mihailescu, Stefan

    2013-01-01

    Cholinergic signaling mediated by nicotinic receptors has been associated to a large number of physiological and behavioral processes such as learning, memory, attention, food-intake and mood disorders. Although it is well established that many nicotinic actions are mediated through an increase in serotonin (5-HT) release, the physiological mechanisms by which nicotine produces these effects are still unclear. The dorsal raphe nucleus (DRN) contains the major amount of 5-HT neurons projecting to different parts of the brain. DRN also contains nicotinic acetylcholine receptors (nAChRs) located at somatic and presynaptic elements. Nicotine produces both inhibitory and excitatory effects on different subpopulations of 5-HT DRN neurons. In this review, we describe the presynaptic and postsynaptic mechanisms by which nicotine increases the excitability of DRN neurons as well as the subtypes of nAChRs involved. We also describe the inhibitory effects of nicotine and the role of 5-HT1A receptors in this effect. These nicotinic actions modulate the activity of different neuronal subpopulations in the DRN, changing the 5-HT tone in the brain areas where these groups of neurons project. Some of the physiological implications of nicotine-induced 5-HT release are discussed.

  11. Developmental switch of leptin signaling in arcuate nucleus neurons.

    Science.gov (United States)

    Baquero, Arian F; de Solis, Alain J; Lindsley, Sarah R; Kirigiti, Melissa A; Smith, M Susan; Cowley, Michael A; Zeltser, Lori M; Grove, Kevin L

    2014-07-23

    Leptin is well known for its role in the regulation of energy homeostasis in adults, a mechanism that at least partially results from the inhibition of the activity of NPY/AgRP/GABA neurons (NAG) in the arcuate nucleus of the hypothalamus (ARH). During early postnatal development in the rodent, leptin promotes axonal outgrowth from ARH neurons, and preautonomic NAG neurons are particularly responsive to leptin's trophic effects. To begin to understand how leptin could simultaneously promote axonal outgrowth from and inhibit the activity of NAG neurons, we characterized the electrochemical effects of leptin on NAG neurons in mice during early development. Here, we show that NAG neurons do indeed express a functional leptin receptor throughout the early postnatal period in the mouse; however, at postnatal days 13-15, leptin causes membrane depolarization in NAG neurons, rather than the expected hyperpolarization. Leptin action on NAG neurons transitions from stimulatory to inhibitory in the periweaning period, in parallel with the acquisition of functional ATP-sensitive potassium channels. These findings are consistent with the idea that leptin provides an orexigenic drive through the NAG system to help rapidly growing pups meet their energy requirements. Copyright © 2014 the authors 0270-6474/14/349982-13$15.00/0.

  12. Nucleus accumbens core and pathogenesis of compulsive checking

    Science.gov (United States)

    Ballester González, Javier; Dvorkin-Gheva, Anna; Silva, Charmaine; Foster, Jane A.

    2015-01-01

    To investigate the role of the nucleus accumbens core (NAc) in the development of quinpirole-induced compulsive checking, rats received an excitotoxic lesion of NAc or sham lesion and were injected with quinpirole (0.5 mg/kg) or saline; development of checking behavior was monitored for 10 biweekly tests. The results showed that even after the NAc lesion, quinpirole still induced compulsive checking, suggesting that the pathogenic effects produced by quinpirole lie outside the NAc. Although the NAc lesion did not prevent the induction of compulsive checking, it altered how quickly it develops, suggesting that the NAc normally contributes toward the induction of compulsive checking. Saline-treated rats with an NAc lesion were hyperactive, but did not develop compulsive checking, indicating that hyperactivity by itself is not sufficient for the pathogenesis of compulsive checking. It is proposed that compulsive checking is the exaggerated output of a security motivation system and that the NAc serves as a neural hub for coordinating the orderly activity of neural modules of this motivational system. Evidence is considered suggesting that the neurobiological condition for the pathogenesis of compulsive checking is two-fold: activation of dopamine D2/D3 receptors without concurrent stimulation of D1-like receptors and long-term plastic changes related to quinpirole-induced sensitization. PMID:25426580

  13. Comparative study of alpha + nucleus elastic scattering using different models

    Science.gov (United States)

    Al-Ghamdi, A. H.; Ibraheem, Awad A.; El-Azab Farid, M.

    2015-01-01

    The alpha (α) elastic scattering from different targets potential over the energy range 10-240 MeV has been analyzed in the framework of the single-folding (SF) optical model. Four targets are considered, namely, 24Mg, 28Si, 32S and 40Ca. The SF calculations for the real central part of the nuclear optical potential are performed by folding an effective α-α interaction with the α-cluster distribution density in the target nucleus. The imaginary part of the optical potential is expressed in the phenomenological Woods-Saxon (WS) form. The calculated angular distributions of the elastic scattering differential cross-section using the derived semimicroscopic potentials successfully reproduce 36 sets of data all over the measured angular ranges. The obtained results confirm the validity of the α-cluster structure of the considered nuclei. For the sake of comparison, the same sets of data are reanalyzed using microscopic double-folded optical potentials based upon the density-dependent Jeukenne-Lejeune-Mahaux (JLM) effective nucleon-nucleon interaction.

  14. The thalamic reticular nucleus: structure, function and concept.

    Science.gov (United States)

    Pinault, Didier

    2004-08-01

    On the basis of theoretical, anatomical, psychological and physiological considerations, Francis Crick (1984) proposed that, during selective attention, the thalamic reticular nucleus (TRN) controls the internal attentional searchlight that simultaneously highlights all the neural circuits called on by the object of attention. In other words, he submitted that during either perception, or the preparation and execution of any cognitive and/or motor task, the TRN sets all the corresponding thalamocortical (TC) circuits in motion. Over the last two decades, behavioural, electrophysiological, anatomical and neurochemical findings have been accumulating, supporting the complex nature of the TRN and raising questions about the validity of this speculative hypothesis. Indeed, our knowledge of the actual functioning of the TRN is still sprinkled with unresolved questions. Therefore, the time has come to join forces and discuss some recent cellular and network findings concerning this diencephalic GABAergic structure, which plays important roles during various states of consciousness. On the whole, the present critical survey emphasizes the TRN's complexity, and provides arguments combining anatomy, physiology and cognitive psychology.

  15. Examining exotic structure of proton-rich nucleus $^{23}$Al

    CERN Document Server

    Fang, D Q; Ma, C W; Wang, K; Yan, T Z; Ma, Y G; Cai, X Z; Shen, W Q; Ren, Z Z; Sun, Z Y; Chen, J G; Tian, W D; Zhong, C; Hosoi, M; Izumikawa, T; Kanungo, R; Nakajima, S; Ohnishi, T; Ohtsubo, T; Ozawa, A; Suda, T; Sugawara, K; Suzuki, T; Takisawa, A; Tanaka, K; Yamaguchi, T; Tanihata, I

    2007-01-01

    The longitudinal momentum distribution (P_{//}) of fragments after one-proton removal from ^{23} Al and reaction cross sections (\\sigma_R) for ^{23,24} Al on carbon target at 74A MeV have been measured. The ^{23,24} Al ions were produced through projectile fragmentation of 135 A MeV ^{28} Si primary beam using RIPS fragment separator at RIKEN. P_{//} is measured by a direct time-of-flight (TOF) technique, while \\sigma_R is determined using a transmission method. An enhancement in \\sigma_R is observed for ^{23} Al compared with ^{24} Al. The P_{//} for ^{22} Mg fragments from ^{23} Al breakup has been obtained for the first time. FWHM of the distributions has been determined to be 232 \\pm 28 MeV/c. The experimental data are discussed by using Few-Body Glauber model. Analysis of P_{//} demonstrates a dominant d-wave configuration for the valence proton in ground state of ^{23} Al, indicating that ^{23} Al is not a proton halo nucleus.

  16. Caudate Nucleus in Retrieval of Trace Eyeblink Conditioning after Consolidation

    Science.gov (United States)

    Flores, Luke C.; Disterhoft, John F.

    2013-01-01

    Trace eyeblink conditioning (EBC) is an associative learning task in which a stimulus-free trace period separates the presentation of a behaviorally neutral conditioned stimulus (CS, whisker stimulation) from a behaviorally salient unconditioned stimulus (US, airpuff to the eye). Repeated pairings of the CS with the US results in the emergence of the conditioned response (CR, eyeblink following CS presentation and preceding US presentation). The goal of these experiments was to determine whether the caudate nucleus (CN) plays a role in retrieval of previously acquired trace EBC after memory consolidation. Lesions of the CN were made one month after initial trace EBC. CN lesioned rabbits performed fewer adaptive CRs and more short-latency non-adaptive responses than sham lesioned controls. They were not able to improve their CR performance after consolidation as were controls. Single unit recordings taken from separate cohorts of rabbits demonstrated that neurons in the CN were still responsive to the CS and US one month after initial trace EBC, particularly in the medial and ventral CN on trials when a CR occurred. The proportion of rate increasing neurons was higher in trace conditioned than in pseudo conditioned rabbits. Neurons in regions destroyed in the behavioral experiment demonstrated prolonged firing during the trace period, which might underlie the results from the behavioral experiment. These data demonstrate that the CN plays an important role in retrieval of a previously learned associative task after memory consolidation has occurred. PMID:23407942

  17. Thalamocortical projections of the anteroventral thalamic nucleus in the rabbit.

    Science.gov (United States)

    Shibata, Hideshi; Yoshiko, Honda

    2015-04-01

    The anterior thalamic nuclei are one of the regions that play critical roles in behavioral learning and memory functions. A part of the anterior thalamic nuclei, the anteroventral nucleus (AV) is well developed and differentiated into the parvocellular (AVp) and magnocellular (AVm) division in the rabbit. The AV is crucial for learning discriminative avoidance conditioning. Although communication between the AV and cortex is considered important in learning, little is known about the neural connections of the AV in the rabbit. Thus, this study used anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin B subunit to examine the organization of the thalamocortical projections of the AV. Our data show that each division of the AV provides a unique set of projections to restricted regions and layers of the retrosplenial cortex and presubiculum. In addition, the AVp projects to layers I and IV of retrosplenial areas 29 and 30 and to layers I and VI of the presubiculum. The dorsolateral AVm projects to layers I and IV of area 29 and to layers I, III, and V of the presubiculum. However, the ventromedial AVm only projects to layer I of area 29. These projections are generally organized such that the rostral-to-caudal axis of the AV corresponds to the caudal-to-rostral axis of the retrosplenial cortex and to the temporal-to-septal axis of the presubiculum. These findings suggest distinct functional roles played by each division of the AV in the learning and memory functions. © 2014 Wiley Periodicals, Inc.

  18. Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson's disease.

    Science.gov (United States)

    Serranová, Tereza; Jech, Robert; Dušek, Petr; Sieger, Tomáš; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen

    2011-10-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinson's disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age ± SD, 58.3 ± 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty-four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P weight gain. Copyright © 2011 Movement Disorder Society.

  19. Targeting of nucleus-encoded proteins to chloroplasts in plants.

    Science.gov (United States)

    Jarvis, Paul

    2008-07-01

    Most chloroplast proteins are encoded in the nucleus and synthesized on free, cytosolic ribosomes in precursor form. Each precursor has an amino-terminal extension called a transit peptide, which directs the protein through a post-translational targeting pathway and is removed upon arrival inside the organelle. This 'protein import' process is mediated by the coordinate action of two multiprotein complexes, one in each of the envelope membranes: the TOC and TIC (Translocon at the Outer/ Inner envelope membrane of Chloroplasts) machines. Many components of these complexes have been identified biochemically in pea; these include transit peptide receptors, channel proteins, and molecular chaperones. Intriguingly, the Arabidopsis genome encodes multiple, homologous genes for receptor components of the TOC complex. Careful analysis indicated that the different receptor isoforms operate in different import pathways with distinct precursor recognition specificities. These 'substrate-specific' import pathways might play a role in the differentiation of different plastid types, and/or act to prevent deleterious competition effects between abundant and nonabundant precursors. Until recently, all proteins destined for internal chloroplast compartments were thought to possess a cleavable transit peptide, and to engage the TOC/TIC machinery. New studies using proteomics and other approaches have revealed that this is far from true. Remarkably, a significant number of chloroplast proteins are transported via a pathway that involves the endoplasmic reticulum and Golgi apparatus. Other recent reports have elucidated an intriguing array of protein targeting routes leading to the envelope membranes themselves.

  20. On Parallel Streams through the Mouse Dorsal Lateral Geniculate Nucleus

    Directory of Open Access Journals (Sweden)

    Daniel eDenman

    2016-03-01

    Full Text Available The mouse visual system is an emerging model for the study of cortical and thalamic circuit function. To maximize the usefulness of this model system, it is important to analyze the similarities and differences between the organization of all levels of the murid visual system with other, better studied systems (e.g., non-human primates and the domestic cat. While the understanding of mouse retina and cortex has expanded rapidly, less is known about mouse dorsal lateral geniculate nucleus (dLGN. Here, we study whether parallel processing streams exist in mouse dLGN. We use a battery of stimuli that have been previously shown to successfully distinguish parallel streams in other species: electrical stimulation of the optic chiasm, contrast-reversing stationary gratings at varying spatial phase, drifting sinusoidal gratings, dense noise for receptive field reconstruction, and frozen contrast-modulating noise. As in the optic nerves of domestic cats and non-human primates, we find evidence for multiple conduction velocity groups after optic chiasm stimulation. As in so-called ‘visual mammals’, we find a subpopulation of mouse dLGN cells showing non-linear spatial summation. However, differences in stimulus selectivity and sensitivity do not provide sufficient basis for identification of clearly distinct classes of relay cells. Nevertheless, consistent with presumptively homologous status of dLGNs of all mammals, there are substantial similarities between response properties of mouse dLGN neurons and those of cats and primates.

  1. Multiparametric characterization of neuronal subpopulations in the ventrolateral preoptic nucleus.

    Science.gov (United States)

    Dubourget, Romain; Sangare, Aude; Geoffroy, Hélène; Gallopin, Thierry; Rancillac, Armelle

    2017-04-01

    The characterization of neuronal properties is a necessary first step toward understanding how the ventrolateral preoptic nucleus (VLPO) neuronal network regulates slow-wave sleep (SWS). Indeed, the electrophysiological heterogeneity of VLPO neurons suggests the existence of subtypes that could differently contribute in SWS induction and maintenance. The aim of the present study was to define cell classes in the VLPO using an unsupervised clustering classification method. Electrophysiological features extracted from 289 neurons recorded in whole-cell patch-clamp allowed the identification of three main classes of VLPO neurons subdivided into five distinct subpopulations (cluster 1, 2a, 2b, 3a and 3b). The high occurrence of a low-threshold calcium spike (LTS) was one of the most distinctive features of cluster 1 and 3. Since sleep-promoting neurons are generally identified by their ability to generate an LTS and by their inhibitory response to noradrenaline (NA), 189 neurons from our dataset were also tested for this neurotransmitter. Neurons from cluster 3 were the most frequently inhibited by NA. Biocytin labeling and Neurolucida reconstructions of 112 neurons furthermore revealed a small dendritic arbor of cluster 3b neurons compared, in particular, to cluster 2b neurons. Altogether, we performed an exhaustive characterization of VLPO neuronal subtypes that is a crucial step toward a better understanding of the neuronal network within the VLPO and thereby sleep physiology.

  2. Sex hormone receptors are present in the human suprachiasmatic nucleus.

    Science.gov (United States)

    Kruijver, Frank P M; Swaab, Dick F

    2002-05-01

    The suprachiasmatic nucleus (SCN) is the clock of the brain that orchestrates circadian and circannual biological rhythms, such as the rhythms of hormones, body temperature, sleep and mood. These rhythms are frequently disturbed in menopause and even more so in dementia and can be restored in postmenopausal women by sex hormone replacement therapy (SHRT). Although it seems clear, both from clinical and experimental studies, that sex hormones influence circadian rhythms, it is not known whether this is by a direct or an indirect effect on the SCN. Therefore, using immunocytochemistry in the present study, we investigated whether the human SCN expresses sex hormone receptors in 5 premenopausal women and 5 young men. SCN neurons appeared to contain estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta) and progesterone receptors. Median ratings of ER immunoreactivity per individual and per gender group revealed a statistically significantly stronger nuclear ERalpha expression pattern in female SCN neurons (p sexual dimorphic tendency was observed for nuclear ERbeta (p > 0.1) and progesterone receptors (p > 0.7). These data seem to support previously reported functional and structural SCN differences in relation to sex and sexual orientation and indicate for the first time that estrogen and progesterone may act directly on neurons of the human biological clock. In addition, the present findings provide a potential neuroendocrine mechanism by which SHRT can act to improve or restore SCN-related rhythm disturbances, such as body temperature, sleep and mood. Copyright 2002 S. Karger AG, Basel

  3. Dust evolution with active galactic nucleus feedback in elliptical galaxies

    Science.gov (United States)

    Hirashita, Hiroyuki; Nozawa, Takaya

    2017-12-01

    We have recently suggested that dust growth in the cold gas phase dominates the dust abundance in elliptical galaxies while dust is efficiently destroyed in the hot X-ray emitting plasma (hot gas). In order to understand the dust evolution in elliptical galaxies, we construct a simple model that includes dust growth in the cold gas and dust destruction in the hot gas. We also take into account the effect of mass exchange between these two gas components induced by active galactic nucleus (AGN) feedback. We survey reasonable ranges of the relevant parameters in the model and find that AGN feedback cycles actually produce a variety in cold gas mass and dust-to-gas ratio. By comparing with an observational sample of nearby elliptical galaxies, we find that, although the dust-to-gas ratio varies by an order of magnitude in our model, the entire range of the observed dust-to-gas ratios is difficult to be reproduced under a single parameter set. Variation of the dust growth efficiency is the most probable solution to explain the large variety in dust-to-gas ratio of the observational sample. Therefore, dust growth can play a central role in creating the variation in dust-to-gas ratio through the AGN feedback cycle and through the variation in dust growth efficiency.

  4. Lateral cervical nucleus projections to periaqueductal gray matter in cat.

    Science.gov (United States)

    Mouton, Leonora J; Klop, Esther-Marije; Broman, Jonas; Zhang, Mengliang; Holstege, Gert

    2004-04-12

    The midbrain periaqueductal gray matter (PAG) integrates the basic responses necessary for survival of individuals and species. Examples are defense behaviors such as fight, flight, and freezing, but also sexual behavior, vocalization, and micturition. To control these behaviors the PAG depends on strong input from more rostrally located limbic structures, as well as from afferent input from the lower brainstem and spinal cord. Mouton and Holstege (2000, J Comp Neurol 428:389-410) showed that there exist at least five different groups of spino-PAG neurons, each of which is thought to subserve a specific function. The lateral cervical nucleus (LCN) in the upper cervical cord is not among these five groups. The LCN relays information from hair receptors and noxious information and projects strongly to the contralateral ventroposterior and posterior regions of thalamus and to intermediate and deep tectal layers. The question is whether the LCN also projects to the PAG. The present study in cat, using retrograde and anterograde tracing techniques, showed that neurons located in the lateral two-thirds of the LCN send fibers to the lateral part of the PAG, predominantly at rostrocaudal levels A0.6-P0.2. This part of the PAG is known to be involved in flight behavior. A concept is put forward according to which the LCN-PAG pathway alerts the animal about the presence of cutaneous stimuli that might represent danger, necessitating flight. J. Comp. Neurol. 471:434-445, 2004. Copyright 2004 Wiley-Liss, Inc.

  5. The mesencephalic nucleus of the trigeminal nerve and the SIDS.

    Science.gov (United States)

    Andrisani, Giovanni; Andrisani, Giorgia

    2015-01-01

    Sudden infant death syndrome (SIDS) is a major cause of infant mortality throughout the world, yet its cause and mechanism of action remain poorly understood. Here, we discuss a novel model of the etiology of SIDS which ties together what is known about the brain regions thought to be affected in SIDS infants with a defined neuroanatomical circuit and a documented preventative factor in young children. We propose that SIDS occurs due to a lack of sufficient development and plasticity of glutamatergic synapses in the mesencephalic nucleus of the trigeminal nerve (Me5) and reticular formation (RF) of the brainstem. This model is supported by evidence of brainstem dysfunction in SIDS as well as evidence of signaling through the Me5 and RF in another means of regulating cortical arousal. Furthermore, long-term plasticity of glutamatergic synapses is well known to play a critical role in learning and memory in other regions of the brain, implying that those mechanisms may also be relevant in the development of brainstem circuitry. This model clearly explains why SIDS deaths appear so suddenly with little pathological explanation and suggests a potentially novel way to prevent these deaths from occurring. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Nucleus accumbens shell moderates preference bias during voluntary choice behavior.

    Science.gov (United States)

    Jang, Hyeran; Jung, Kanghoon; Jeong, Jaehoon; Park, Sang Ki; Kralik, Jerald D; Jeong, Jaeseung

    2017-09-01

    The nucleus accumbens (NAc) shell lies anatomically at a critical intersection within the brain's reward system circuitry, however, its role in voluntary choice behavior remains unclear. Rats with electrolytic lesions in the NAc shell were tested in a novel foraging paradigm. Over a continuous two-week period they freely chose among four nutritionally identical but differently flavored food pellets by pressing corresponding levers. We examined the lesion's effects on three behavioral dynamics components: motivation (when to eat), preference bias (what to choose) and persistence (how long to repeat the same choice). The lesion led to a marked increase in the preference bias: i.e., increased selection of the most-preferred choice option, and decreased selection of the others. We found no effects on any other behavioral measures, suggesting no effect on motivation or choice persistence. The results implicate the NAc shell in moderating the instrumental valuation process by inhibiting excessive bias toward preferred choice options. © The Author (2017). Published by Oxford University Press.

  7. Depolarizing actions of hydrogen sulfide on hypothalamic paraventricular nucleus neurons.

    Directory of Open Access Journals (Sweden)

    C Sahara Khademullah

    Full Text Available Hydrogen sulfide (H2S is a novel neurotransmitter that has been shown to influence cardiovascular functions as well and corticotrophin hormone (CRH secretion. Since the paraventricular nucleus of the hypothalamus (PVN is a central relay center for autonomic and endocrine functions, we sought to investigate the effects of H2S on the neuronal population of the PVN. Whole cell current clamp recordings were acquired from the PVN neurons and sodium hydrosulfide hydrate (NaHS was bath applied at various concentrations (0.1, 1, 10, and 50 mM. NaHS (1, 10, and 50 mM elicited a concentration-response relationship from the majority of recorded neurons, with almost exclusively depolarizing effects following administration. Cells responded and recovered from NaHS administration quickly and the effects were repeatable. Input differences from baseline and during the NaHS-induced depolarization uncovered a biphasic response, implicating both a potassium and non-selective cation conductance. The results from the neuronal population of the PVN shed light on the possible physiological role that H2S has in autonomic and endocrine function.

  8. Elastic and inelastic scattering of neutrons on 238U nucleus

    Directory of Open Access Journals (Sweden)

    Capote R.

    2014-04-01

    Full Text Available Advanced modelling of neutron induced reactions on the 238U nucleus is aimed at improving our knowledge of neutron scattering. Capture and fission channels are well constrained by available experimental data and neutron standard evaluation. A focus of this contribution is on elastic and inelastic scattering cross sections. The employed nuclear reaction model includes – a new rotational-vibrational dispersive optical model potential coupling the low-lying collective bands of vibrational character observed in even-even actinides; – the Engelbrecht-Weidenmüller transformation allowing for inclusion of compound-direct interference effects; – and a multi-humped fission barrier with absorption in the secondary well described within the optical model for fission. Impact of the advanced modelling on elastic and inelastic scattering cross sections including angular distributions and emission spectra is assessed both by comparison with selected microscopic experimental data and integral criticality benchmarks including measured reaction rates (e.g. JEMIMA, FLAPTOP and BIG TEN. Benchmark calculations provided feedback to improve the reaction modelling. Improvement of existing libraries will be discussed.

  9. In vivo histamine voltammetry in the mouse premammillary nucleus.

    Science.gov (United States)

    Samaranayake, Srimal; Abdalla, Aya; Robke, Rhiannon; Wood, Kevin M; Zeqja, Anisa; Hashemi, Parastoo

    2015-06-07

    Histamine plays a major role in the mediation of allergic reactions such as peripheral inflammation. This classical monoamine is also a neurotransmitter involved in the central nervous system but its role in this context is poorly understood. Studying histamine neurotransmission is important due to its implications in many neurological disorders. The sensitivity, selectivity and high temporal resolution of fast scan cyclic voltammetry (FSCV) offer many advantages for studying electroactive neurotransmitters. Histamine has previously been studied with FSCV; however, the lack of a robust Faradaic electrochemical signal makes it difficult to selectively identify histamine in complex media, as found in vivo. In this work, we optimize an electrochemical waveform that provides a stimulation-locked and unique electrochemical signal towards histamine. We describe in vitro waveform optimization and a novel in vivo physiological model for stimulating histamine release in the mouse premammillary nucleus via stimulation of the medial forebrain bundle. We demonstrate that a robust signal can be used to effectively identify histamine and characterize its in vivo kinetics.

  10. Contour Detection of Leukocyte Cell Nucleus Using Morphological Image

    Science.gov (United States)

    Supriyanti, R.; Satrio, G. P.; Ramadhani, Y.; Siswandari, W.

    2017-04-01

    Leukocytes are blood cells that do not contain color pigments. Leukocyte function to the tool body’s defenses. Abnormal forms of leukocytes can be a sign of serious diseases such example is leukemia. Most laboratories still use cell morphology examination to assist the diagnosis of illness associated with white blood cells such example is leukemia because of limited resources, both infrastructure, and human resources as happens in developing nations, such as Indonesia. This examination is less expensive and quicker process. However, morphological review requires the expertise of a specialist clinical pathology were limited. This process is sometimes less valid cause in some cases trying to differentiate morphology blast cells into the type of myoblasts, lymphoblast, monoblast, or erythroblast thus potentially misdiagnosis. The goal of this research is to develop a detection device types of blood cells automatically as lower-priced, easy to use and accurate so that the tool can be distributed across all units in existing health services throughout Indonesia and in particular for remote areas. However, because the variables used in the identification of abnormal leukocytes are very complex, in this paper, we emphasize on the contour detection of leukocyte cell nucleus using the morphological image. The results show that this method is promising for further development.

  11. Nucleus accumbens shell moderates preference bias during voluntary choice behavior

    Science.gov (United States)

    Jang, Hyeran; Jung, Kanghoon; Jeong, Jaehoon; Park, Sang Ki; Kralik, Jerald D.

    2017-01-01

    Abstract The nucleus accumbens (NAc) shell lies anatomically at a critical intersection within the brain’s reward system circuitry, however, its role in voluntary choice behavior remains unclear. Rats with electrolytic lesions in the NAc shell were tested in a novel foraging paradigm. Over a continuous two-week period they freely chose among four nutritionally identical but differently flavored food pellets by pressing corresponding levers. We examined the lesion’s effects on three behavioral dynamics components: motivation (when to eat), preference bias (what to choose) and persistence (how long to repeat the same choice). The lesion led to a marked increase in the preference bias: i.e., increased selection of the most-preferred choice option, and decreased selection of the others. We found no effects on any other behavioral measures, suggesting no effect on motivation or choice persistence. The results implicate the NAc shell in moderating the instrumental valuation process by inhibiting excessive bias toward preferred choice options. PMID:28992274

  12. The hypothalamic arcuate nucleus and the control of peripheral substrates.

    Science.gov (United States)

    Joly-Amado, Aurélie; Cansell, Céline; Denis, Raphaël G P; Delbes, Anne-Sophie; Castel, Julien; Martinez, Sarah; Luquet, Serge

    2014-10-01

    The arcuate nucleus (ARC) of the hypothalamus is particularly regarded as a critical platform that integrates circulating signals of hunger and satiety reflecting energy stores and nutrient availability. Among ARC neurons, pro-opiomelanocortin (POMC) and agouti-related protein and neuropeptide Y (NPY/AgRP neurons) are considered as two opposing branches of the melanocortin signaling pathway. Integration of circulating signals of hunger and satiety results in the release of the melanocortin receptor ligand α-melanocyte-stimulating hormone (αMSH) by the POMC neurons system and decreases feeding and increases energy expenditure. The orexigenic/anabolic action of NPY/AgRP neurons is believed to rely essentially on their inhibitory input onto POMC neurons and second-orders targets. Recent updates in the field have casted a new light on the role of the ARC neurons in the coordinated regulation of peripheral organs involved in the control of nutrient storage, transformation and substrate utilization independent of food intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Kleptochloroplast Enlargement, Karyoklepty and the Distribution of the Cryptomonad Nucleus in Nusuttodinium (= Gymnodinium) aeruginosum (Dinophyceae).

    Science.gov (United States)

    Onuma, Ryo; Horiguchi, Takeo

    2015-05-01

    The unarmoured freshwater dinoflagellate Nusuttodinium (= Gymnodinium) aeruginosum retains a cryptomonad-derived kleptochloroplast and nucleus, the former of which fills the bulk of its cell volume. The paucity of studies following morphological changes to the kleptochloroplast with time make it unclear how the kleptochloroplast enlarges and why the cell ultimately loses the cryptomonad nucleus. We observed, both at the light and electron microscope level, morphological changes to the kleptochloroplast incurred by the enlargement process under culture conditions. The distribution of the cryptomonad nucleus after host cell division was also investigated. The volume of the kleptochloroplast increased more than 20-fold, within 120h of ingestion of the cryptomonad. Host cell division was not preceded by cryptomonad karyokinesis so that only one of the daughter cells inherited a cryptomonad nucleus. The fate of all daughter cells originating from a single cell through five generations was closely monitored, and this observation revealed that the cell that inherited the cryptomonad nucleus consistently possessed the largest kleptochloroplast for that generation. Therefore, this study suggests that some important cryptomonad nucleus division mechanism is lost during ingestion process, and that the cryptomonad nucleus carries important information for the enlargement of the kleptochloroplast. Copyright © 2015 Elsevier GmbH. All rights reserved.

  14. The Efferent Connections Of The Nucleus Of The Optic Tract And The Superior Colliculus In The Rabbit

    NARCIS (Netherlands)

    Holstege, Gert; Collewijn, Han

    1982-01-01

    3H-leucine injections were made in tectal and pretectal areas in the rabbit. After injections in the nucleus of the optic tract (NOT) labeled fibers were distributed bilaterally to the superior colliculus, the dorsal part of the medial geniculate nucleus (MGd), and the pulvinar nucleus, and

  15. Thermodynamics of droplet formation around a soluble condensation nucleus in the atmosphere of a solvent vapor.

    Science.gov (United States)

    Shchekin, A K; Shabaev, I V; Rusanov, A I

    2008-12-07

    An expression for the work of formation of a spherical droplet condensing on a soluble condensation nucleus out of a solvent vapor is derived. The dependence of the formation work on the solvent vapor chemical potential and the droplet and the nucleus residue sizes is analyzed. The balance of the solute matter between the liquid film and the nucleus residue and the effect of overlapping the surface layers of the thin film have been taken into account. It is shown that the equations of the chemical equilibrium of a solute and a solvent in the droplet, resulting from the generating properties of the formation work, coincide with the generalized Gibbs-Kelvin-Kohler and Ostwald-Freundlich equations. The numerical solution of these equations at a fixed number of molecules of the nucleus matter (at an initial size of the nucleus specified) has been performed in the case of the solvent vapor undersaturated over the bulk liquid solvent phase. The solution links the equilibrium sizes of the droplet and the soluble nucleus residue with the chemical potential or the pressure of the solvent vapor saturated over the droplet. It also determines the limiting sizes of the droplet with small nucleus residue above which the chemical equilibrium of the residue surface and the solution film does not exist. The existence of the limiting sizes is responsible for the specific behavior of the droplet thermodynamic characteristics and the work of droplet formation at deliquescence transition from the droplet state with a partly dissolved nucleus to the state of complete dissolution of the nucleus.

  16. Bradycardic effects mediated by activation of G protein-coupled estrogen receptor in rat nucleus ambiguus.

    Science.gov (United States)

    Brailoiu, G Cristina; Arterburn, Jeffrey B; Oprea, Tudor I; Chitravanshi, Vineet C; Brailoiu, Eugen

    2013-03-01

    The G protein-coupled estrogen receptor (GPER) has been identified in several brain regions, including cholinergic neurons of the nucleus ambiguus, which are critical for parasympathetic cardiac regulation. Using calcium imaging and electrophysiological techniques, microinjection into the nucleus ambiguus and blood pressure measurement, we examined the in vitro and in vivo effects of GPER activation in nucleus ambiguus neurons. A GPER selective agonist, G-1, produced a sustained increase in cytosolic Ca(2+) concentration in a concentration-dependent manner in retrogradely labelled cardiac vagal neurons of nucleus ambiguus. The increase in cytosolic Ca(2+) produced by G-1 was abolished by pretreatment with G36, a GPER antagonist. G-1 depolarized cultured cardiac vagal neurons of the nucleus ambiguus. The excitatory effect of G-1 was also identified by whole-cell visual patch-clamp recordings in nucleus ambiguus neurons, in medullary slices. To validate the physiological relevance of our in vitro studies, we carried out in vivo experiments. Microinjection of G-1 into the nucleus ambiguus elicited a decrease in heart rate; the effect was blocked by prior microinjection of G36. Systemic injection of G-1, in addition to a previously reported decrease in blood pressure, also reduced the heart rate. The G-1-induced bradycardia was prevented by systemic injection of atropine, a muscarinic antagonist, or by bilateral microinjection of G36 into the nucleus ambiguus. Our results indicate that GPER-mediated bradycardia occurs via activation of cardiac parasympathetic neurons of the nucleus ambiguus and support the involvement of the GPER in the modulation of cardiac vagal tone.

  17. A stereological study of the mediodorsal thalamic nucleus in Down syndrome

    DEFF Research Database (Denmark)

    Karlsen, A S; Korbo, S; Uylings, H B M

    2014-01-01

    The total number of neurons and glial cells in the mediodorsal thalamic (MDT) nucleus of four aged females with Down syndrome (DS; mean age 69years) was estimated and compared to six age- and sex-matched controls. The MDT nucleus was delineated on coronal sections, and cell numbers (large and small...... neurons, oligodendrocytes, and astrocytes) were estimated using the optical fractionator technique. The DS brains had an average of 3.41×10(6) total neurons in the MDT nucleus in contrast to 5.97×10(6) in the controls, with no overlap (2p=0.004), affecting large (projecting) and small (local inhibitory...

  18. A role of nucleus accumbens dopamine receptors in the nucleus accumbens core, but not shell, in fear prediction error.

    Science.gov (United States)

    Li, Susan S Y; McNally, Gavan P

    2015-08-01

    Two experiments used an associative blocking design to study the role of dopamine receptors in the nucleus accumbens shell (AcbSh) and core (AcbC) in fear prediction error. Rats in the experimental groups were trained to a visual fear-conditioned stimulus (conditional stimulus [CS]) A in Stage I, whereas rats in the control groups were not. In Stage II, all rats received compound fear conditioning of the visual CSA and an auditory CSB. Rats were later tested for their fear responses to CSB. All rats received microinjections of saline or the D1-D2 receptor antagonist cis-(z)-flupenthixol prior to Stage II. These microinjections targeted either the AcbSh (Experiment 1) or the AcbC (Experiment 2). In each experiment, Stage I fear conditioning of CSA blocked fear learning to CSB. Microinjection of cis-(z)-flupenthixol (10 or 20 μg) into the AcbSh (Experiment 1) had no effect on fear learning or associative blocking. In contrast, microinjection of cis-(z)-flupenthixol (10 or 20 μg) into the AcbC (Experiment 2) attenuated blocking and so enabled fear learning to CSB. These results identify the AcbC as the critical locus for dopamine receptor contributions to fear prediction error and the associative blocking of fear learning. (c) 2015 APA, all rights reserved).

  19. $N-N$, $P_{T}-N$ and $P_{T}-P_{T}$ fluctuations in nucleus-nucleus collisions at the NA61/SHINE experiment arXiv

    CERN Document Server

    Andronov, Evgeny

    The NA61/SHINE experiment aims to discover the critical point of strongly interacting matter and study the properties of the onset of deconfinement. For these goals a scan of the two dimensional phase diagram ($T-\\mu_{B}$) is being performed at the SPS by measurements of hadron production in proton-proton, proton-nucleus and nucleus-nucleus interactions as a function of collision energy. This paper presents preliminary results from Be+Be collisions on pseudorapidity dependences of transverse momentum and multiplicity fluctuations expressed in terms of strongly intensive quantities. It is shown that non-trivial effects evolve from the Poissonian-like fluctuations for small pseudorapidity intervals with expansion of the acceptance. These fluctuations are supposed to be sensitive to the existence of the critical point. The results will be compared to the predictions from the EPOS model.

  20. Atmospheric Aerosols: Cloud Condensation Nucleus Activity of Selected Organic Molecules

    Science.gov (United States)

    Rosenorn, T.; Henning, S.; Hartz, K. H.; Kiss, G.; Pandis, S.; Bilde, M.

    2005-12-01

    Gas/particle partitioning of vapors in the atmosphere plays a major role in both climate through micro meteorology and in the physical and chemical processes of a single particle. This work has focused on the cloud droplet activation of a number of pure and mixed compounds. The means used to investigate these processes have been the University of Copenhagen cloud condensation nucleus counter setup and the Carnegie Mellon University CCNC setup. The importance of correct water activity modeling has been addressed and it has been pointed out that the molecular mass is an important parameter to consider when choosing model compounds for cloud activation models. It was shown that both traditional Kohler theory and Kohler theory modified to account for limited solubility reproduce measurements of soluble compounds well. For less soluble compounds it is necessary to use Kohler theory modified to account for limited solubility. It was also shown that this works for mixtures of compounds containing both inorganic salts and dicarboxylic acids. It has also been shown that particle phase and humidity history is important for activation behavior of particles consisting of two slightly soluble organic substances (succinic and adipic acid) and a soluble salt (NaCl). Model parameters for terpene oxidation product cloud activation have been derived. These are based on two sets of average parameters covering monoterpene oxidation products and sesquiterpene oxidation products. All parameters except the solubility were estimated and an effective solubility was calculated as the fitting parameter. The average solubility of the model compound found for mono terpene oxidation products is similar to those of sodium chloride and ammonium sulfate; however the higher molecular weight leads to a slightly higher activation diameter at fixed supersaturation. On a molar basis the monoterpene oxidation products show a 1.5 times higher effective solubility than the sesquiterpene oxidation products.

  1. Visual signal processing in the macaque lateral geniculate nucleus.

    Science.gov (United States)

    Seim, Thorstein; Valberg, Arne; Lee, Barry B

    2012-03-01

    Comparisons of S- or prepotential activity, thought to derive from a retinal ganglion cell afferent, with the activity of relay cells of the lateral geniculate nucleus (LGN) have sometimes implied a loss, or leak, of visual information. The idea of the "leaky" relay cell is reconsidered in the present analysis of prepotential firing and LGN responses of color-opponent cells of the macaque LGN to stimuli varying in size, relative luminance, and spectral distribution. Above a threshold prepotential spike frequency, called the signal transfer threshold (STT), there is a range of more than 2 log units of test field luminance that has a 1:1 relationship between prepotential- and LGN-cell firing rates. Consequently, above this threshold, the LGN cell response can be viewed as an extension of prepotential firing (a "nonleaky relay cell"). The STT level decreased when the size of the stimulus increased beyond the classical receptive field center, indicating that the LGN cell is influenced by factors other than the prepotential input. For opponent ON cells, both the excitatory and the inhibitory response decreased similarly when the test field size increased beyond the center of the receptive field. These findings have consequences for the modeling of LGN cell responses and transmission of visual information, particularly for small fields. For instance, for LGN ON cells, information in the prepotential intensity-response curve for firing rates below the STT is left to be discriminated by OFF cells. Consequently, for a given light adaptation, the STT improves the separation of the response range of retinal ganglion cells into "complementary" ON and OFF pathways.

  2. Processing of emotional information in the human subthalamic nucleus.

    Science.gov (United States)

    Buot, Anne; Welter, Marie-Laure; Karachi, Carine; Pochon, Jean-Baptiste; Bardinet, Eric; Yelnik, Jérôme; Mallet, Luc

    2013-12-01

    The subthalamic nucleus (STN) is an efficient target for treating patients with Parkinson's disease as well as patients with obsessive-compulsive disorder (OCD) using high frequency stimulation (HFS). In both Parkinson's disease and OCD patients, STN-HFS can trigger abnormal behaviours, such as hypomania and impulsivity. To investigate if this structure processes emotional information, and whether it depends on motor demands, we recorded subthalamic local field potentials in 16 patients with Parkinson's disease using deep brain stimulation electrodes. Recordings were made with and without dopaminergic treatment while patients performed an emotional categorisation paradigm in which the response varied according to stimulus valence (pleasant, unpleasant and neutral) and to the instruction given (motor, non-motor and passive). Pleasant, unpleasant and neutral stimuli evoked an event related potential (ERP). Without dopamine medication, ERP amplitudes were significantly larger for unpleasant compared with neutral pictures, whatever the response triggered by the stimuli; and the magnitude of this effect was maximal in the ventral part of the STN. No significant difference in ERP amplitude was observed for pleasant pictures. With dopamine medication, ERP amplitudes were significantly increased for pleasant compared with neutral pictures whatever the response triggered by the stimuli, while ERP amplitudes to unpleasant pictures were not modified. These results demonstrate that the ventral part of the STN processes the emotional valence of stimuli independently of the motor context and that dopamine enhances processing of pleasant information. These findings confirm the specific involvement of the STN in emotional processes in human, which may underlie the behavioural changes observed in patients with deep brain stimulation.

  3. Rhythmic Coupling Among Cells in the Suprachiasmatic Nucleus

    Science.gov (United States)

    Colwell, Christopher S.

    2008-01-01

    In mammals, the part of the nervous system responsible for most circadian behavior can be localized to a pair of structures in the hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies suggest that the basic mechanism responsible for the generation of these rhythms is intrinsic to individual cells. There is also evidence that the cells within the SCN are coupled to one another and that this coupling is important for the normal functioning of the circadian system. One mechanism that mediates coordinated electrical activity is direct electrical connections between cells formed by gap junctions. In the present study, we used a brain slice preparation to show that developing SCN cells are dye coupled. Dye coupling was observed in both the ventrolateral and dorsomedial subdivisions of the SCN and was blocked by application of a gap junction inhibitor, halothane. Dye coupling in the SCN appears to be regulated by activity-dependent mechanisms as both tetrodotoxin and the GABAA agonist muscimol inhibited the extent of coupling. Furthermore, acute hyperpolarization of the membrane potential of the original biocytin-filled neuron decreased the extent of coupling. SCN cells were extensively dye coupled during the day when the cells exhibit synchronous neural activity but were minimally dye coupled during the night when the cells are electrically silent. Immunocytochemical analysis provides evidence that a gap-junction—forming protein, connexin32, is expressed in the SCN of postnatal animals. Together the results are consistent with a model in which gap junctions provide a means to couple SCN neurons on a circadian basis. PMID:10861563

  4. GABAergic actions on cholinergic laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Kohlmeier, K A; Kristiansen, Uffe

    2010-01-01

    (IRK) mediated this effect. Further, outward currents were never additive with those induced by application of carbachol, suggesting that they were mediated by activation of GABA(B) receptors linked to the same G(IRK) activated in these cells by muscarinic receptor stimulation. Activation of GABA(B) receptors...

  5. System-size dependence of strangeness production in nucleus-nucleus collisions at $\\sqrt{s_{NN}}$ = 17.3 GeV

    CERN Document Server

    Alt, C; Baatar, B; Barna, D; Bartke, J; Betev, L; Bialkowska, H; Billmeier, A; Blume, C; Boimska, B; Botje, M; Bracinik, J; Bramm, R; Brun, R; Buncic, P; Cerny, V; Christakoglou, P; Chvala, O; Cramer, J G; Csató, P; Darmenov, N; Dimitrov, A; Dinkelaker, P; Eckardt, V; Farantatos, G; Flierl, D; Fodor, Z; Foka, P; Freund, P; Friese, V; Gál, J; Gazdzicki, M; Georgopoulos, G; Gladysz-Dziadus, E; Grebieszkow, K; Hegyi, S; Höhne, C; Kadija, K; Karev, A; Kliemant, M; Kniege, S; Kolesnikov, V I; Kollegger, T; Kornas, E; Korus, R; Kowalski, M; Kraus, I; Kreps, M; Van Leeuwen, M; Lévai, Peter; Litov, L; Lungwitz, B; Makariev, M; Malakhov, A I; Markert, C; Mateev, M; Mayes, B W; Melkumov, G L; Meurer, C; Mischke, A; Mitrovski, M; Molnár, J; Mrówczynski, S; Pálla, G; Panagiotou, A D; Panayotov, D; Petridis, A; Pikna, M; Pinsky, L; Pühlhofer, F; Reid, J G; Renfordt, R; Richard, A; Roland, C; Roland, G; Rybczynski, M; Rybicki, A; Sandoval, A; Sann, H; Schmitz, N; Seyboth, P; Siklér, F; Sitár, B; Skrzypczak, E; Stefanek, G; Stock, R; Ströbele, H; Susa, T; Szentpétery, I; Sziklai, J; Trainor, T A; Trubnikov, V; Varga, D; Vassiliou, M; Veres, G I; Vesztergombi, G; Vranic, D; Wetzler, A; Wlodarczyk, Z; Yoo, I K; Zaranek, J; Zimányi, J

    2005-01-01

    Emission of pi plus or minus , K plus or minus , phi, and Lambda was measured in near-central C + C and Si + Si collisions at 158 AGeV beam energy. Together with earlier data for p + p, S + S, and Pb + Pb, the system-size dependence of relative strangeness production in nucleus-nucleus collisions is obtained. Its fast rise and the saturation observed at about 60 participating nucleons can be understood as the onset of the formation of coherent systems of increasing size. copy 2005 The American Physical Society.

  6. Effect of Decompression Therapy Combined with Joint Mobilization on Patients with Lumbar Herniated Nucleus Pulposus

    National Research Council Canada - National Science Library

    Lee, Younghwa; Lee, Chang-Ryeol; Cho, Misuk

    2012-01-01

    [Purpose] The purpose of this study was to examine the effects of decompression therapy combined with joint mobilization on the pain and range of motion of patients with lumbar herniated nucleus pulposus. [Subjects...

  7. The Developmental Remodeling of Eye‐Specific Afferents in the Ferret Dorsal Lateral Geniculate Nucleus

    National Research Council Canada - National Science Library

    Speer, Colenso M; Mikula, Shawn; Huberman, Andrew D; Chapman, Barbara

    2010-01-01

    Ferret vision mandala. This photo was created by overlapping multiple images of a horizontal section through the central portion of the adult ferret lateral geniculate nucleus and superior colliculus...

  8. Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS

    NARCIS (Netherlands)

    Purba, J. S.; Hofman, M. A.; Portegies, P.; Troost, D.; Swaab, D. F.

    1993-01-01

    The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age

  9. Facebook usage on smartphones and gray matter volume of the nucleus accumbens.

    Science.gov (United States)

    Montag, Christian; Markowetz, Alexander; Blaszkiewicz, Konrad; Andone, Ionut; Lachmann, Bernd; Sariyska, Rayna; Trendafilov, Boris; Eibes, Mark; Kolb, Julia; Reuter, Martin; Weber, Bernd; Markett, Sebastian

    2017-06-30

    A recent study has implicated the nucleus accumbens of the ventral striatum in explaining why online-users spend time on the social network platform Facebook. Here, higher activity of the nucleus accumbens was associated with gaining reputation on social media. In the present study, we touched a related research field. We recorded the actual Facebook usage of N=62 participants on their smartphones over the course of five weeks and correlated summary measures of Facebook use with gray matter volume of the nucleus accumbens. It appeared, that in particular higher daily frequency of checking Facebook on the smartphone was robustly linked with smaller gray matter volumes of the nucleus accumbens. The present study gives additional support for the rewarding aspects of Facebook usage. Moreover, it shows the feasibility to include real life behavior variables in human neuroscientific research. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Capsulotomy and hydroprocedures for nucleus prolapse in manual small incision cataract surgery

    Directory of Open Access Journals (Sweden)

    Venkatesh Rengaraj

    2009-01-01

    Full Text Available Manual small incision cataract surgery (MSICS involves the manual removal of nucleus through a scleral tunnel. To achieve 100% success every time, one has to do a good capsulotomy and should master the technique to prolapse the nucleus into anterior chamber. During conversion from extracapsular cataract surgery to MSICS, one can perform a can-opener capsulotomy and prolapse the nucleus. However, it is safer and better to perform a capsulorrhexis and hydroprolapse the nucleus, as it makes the rest of the steps of MSICS comfortable. Use of trypan blue in white and brown cataracts makes the capsulorrhexis and prolapse simple and safe. Extra caution should be taken in cases with hypermature cataracts with weak zonules and subluxated cataracts.

  11. c-Met must translocate to the nucleus to initiate calcium signals.

    Science.gov (United States)

    Gomes, Dawidson A; Rodrigues, Michele A; Leite, M Fatima; Gomez, Marcus V; Varnai, Peter; Balla, Tamas; Bennett, Anton M; Nathanson, Michael H

    2008-02-15

    Hepatocyte growth factor (HGF) is important for cell proliferation, differentiation, and related activities. HGF acts through its receptor c-Met, which activates downstream signaling pathways. HGF binds to c-Met at the plasma membrane, where it is generally believed that c-Met signaling is initiated. Here we report that c-Met rapidly translocates to the nucleus upon stimulation with HGF. Ca(2+) signals that are induced by HGF result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. Translocation of c-Met to the nucleus depends upon the adaptor protein Gab1 and importin beta1, and formation of Ca(2+) signals in turn depends upon this translocation. HGF may exert its particular effects on cells because it bypasses signaling pathways in the cytoplasm to directly activate signaling pathways in the nucleus.

  12. Effects of damage to median raphe nucleus on ingestive behavior and wheel running activity.

    Science.gov (United States)

    Shahid Salles, M S; Heym, J; Gladfelter, W E

    1979-01-01

    The effects of damage to the median raphe nucleus on the ingestive behavior and wheel running activity of rats were studied. This nucleus was damaged by the placement of either electrolytic or chemical (5,7-dihydroxytryptamine) lesions. After the placement of either type of lesion, wheel running activity was significantly decreased for the duration of the 8 week post-operative period. Although there were transient decreases in both food and water intakes after damage to the median raphe nucleus, these decreases did not appear to result from impairments in neuro-regulatory mechanisms. Rather, the decrease in food intake seemed to be related to the decrease in locomotor activity, and the decrease in water intake appeared to be linked to the decrease in food intake. In some rats with electrolytic lesions in the median raphe nucleus, the decrease in water intake was followed by a transient period of hyperdipsia.

  13. Phenomenological features of two-proton virtual decay of the 45Fe nucleus

    Science.gov (United States)

    Kadmensky, S. G.; Ivankov, Yu. V.; Lyubashevsky, D. E.

    2017-09-01

    On the basis of the theory of diagonal two-proton two-step virtual decays of spherical nuclei that was developed earlier and the superfluid model of the nucleus, the total and partial widths for the two-proton decay of the 45Fe parent nucleus in the ground state to the ground state of the 43Cr daughter nucleus were calculated along with the angular distribution of protons emitted in this decay. The calculated features of this mode of 45Fe decay were shown to be highly sensitive to the choice of form for nucleon shell potentials. It is also shown that there exists a potential such with which one can construct a successful simultaneous description of the experimental total width and the angular distribution of emitted protons for the aforementioned two-proton mode of decay of the 45Fe nucleus.

  14. Projection and synaptic connectivity of trigeminal mesencephalic nucleus neurons controlling jaw reflexes

    National Research Council Canada - National Science Library

    Yoshida, Atsushi; Moritani, Masayuki; Nagase, Yoshitaka; Bae, Yong Chul

    2017-01-01

    Neurons in the trigeminal mesencephalic nucleus (Vmes) receive deep sensation (proprioception) from jaw-closing muscle spindles and periodontal ligaments and project primarily to the jaw-closing motoneuron pool...

  15. The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats

    NARCIS (Netherlands)

    Leon-Mercado, Luis; Herrera Moro Chao, Daniela; Basualdo, María Del Carmen; Kawata, Mitsuhiro; Escobar, Carolina; Buijs, Ruud M.

    2017-01-01

    Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the

  16. Efferent connections of the anterior hypothalamic nucleus: a biocytin study in the cat.

    Science.gov (United States)

    Kanemaru, H; Nakamura, H; Isayama, H; Kawabuchi, M; Tashiro, N

    2000-02-01

    The efferent connections of the anterior hypothalamic nucleus (AH) were examined using biocytin as anterograde tracer in the cat. The results provide several new findings in addition to confirming earlier observations. In the hypothalamus, the AH projections terminated mainly in the medial regions which are related to the defensive, reproductive and feeding behaviors, and autonomic functions. Moreover, we found dense patches of the AH terminals in the medial preoptic area and ventromedial hypothalamic nucleus, which suggests the existence of modular connections between sub-regions of each nucleus. In addition, the AH projected to regions which may be related to the emotional and autonomic responses, i.e., such regions in the amygdala, midline thalamus, septum, subthalamus, and midbrain. The data suggest that the AH may play an important role in the autonomic functions and behaviors between animals, and thus may play a key role in the defensive behavior elicited in the medial preoptic area and ventromedial hypothalamic nucleus.

  17. Nucleus-independent chemical shift criterion for aromaticity in π-extended tetraoxa[8]circulenes

    DEFF Research Database (Denmark)

    Baryshnikov, Gleb V.; Minaev, Boris F.; Pittelkow, Michael

    2013-01-01

    Recently synthesized p-extended symmetrical tetraoxa[8]circulenes that exhibit electroluminescent properties were calculated at the density functional theory (DFT) level using the quantum theory of atoms in molecules (QTAIM) approach to electron density distribution analysis. Nucleus-independent ...

  18. Proton-Nucleus Collisions at the LHC: Scientific Opportunities and Requirements

    CERN Document Server

    Salgado, C A; Arleo, F; Armesto, N; Botje, M; Cacciari, M; Campbell, J; Carli, C; Cole, B; D'Enterria, D; Gelis, F; Guzey, V; Hencken, K; Jacobs, P; Jowett, J M; Klein, S R; Maltoni, F; Morsch, A; Piotrzkowski, K; Qiu, J W; Satogata, T; Sikler, F; Strikman, M; Takai, H; Vogt, R; Wessels, J P; White, S N; Wiedemann, U A; Wyslouch, B; Zhalov, M

    2012-01-01

    Proton-nucleus (p+A) collisions have long been recognized as a crucial component of the physics programme with nuclear beams at high energies, in particular for their reference role to interpret and understand nucleus-nucleus data as well as for their potential to elucidate the partonic structure of matter at low parton fractional momenta (small-x). Here, we summarize the main motivations that make a proton-nucleus run a decisive ingredient for a successful heavy-ion programme at the Large Hadron Collider (LHC) and we present unique scientific opportunities arising from these collisions. We also review the status of ongoing discussions about operation plans for the p+A mode at the LHC.

  19. LEPTIN SIGNALING IN THE NUCLEUS TRACTUS SOLITARII INCREASES SYMPATHETIC NERVE ACTIVITY TO THE KIDNEY

    OpenAIRE

    Mark, Allyn L.; Agassandian, Khristofor; Morgan, Donald A.; Liu, Xuebo; Cassell, Martin D.; Rahmouni, Kamal

    2008-01-01

    The hypothalamic arcuate nucleus was initially regarded as the principal site of leptin action, but there is increasing evidence for functional leptin receptors (Ob-Rb) in extra-hypothalamic sites, including the nucleus tractus solitarii (NTS). We previously demonstrated that arcuate injection of leptin increases sympathetic nerve activity (SNA) to brown adipose tissue (BAT) and kidney. In this study, we tested the hypothesis that leptin signaling in the NTS affects sympathetic neural outflow...

  20. Biocarbon-coated LiFePO4 nucleus nanoparticles enhancing electrochemical performances

    DEFF Research Database (Denmark)

    Zhang, X.G.; Zhang, X.D.; He, W.

    2012-01-01

    We report a green biomimetic method to synthesize biocarbon-coated LiFePO4 nucleus nanoparticles using yeast cells as both a structural template and a biocarbon source for high-power lithium-ion batteries.......We report a green biomimetic method to synthesize biocarbon-coated LiFePO4 nucleus nanoparticles using yeast cells as both a structural template and a biocarbon source for high-power lithium-ion batteries....

  1. Deep Impact Mission: Looking Beneath the Surface of a Cometary Nucleus

    CERN Document Server

    Russell, Christopher T

    2005-01-01

    Deep Impact, or at least part of the flight system, is designed to crash into comet 9P/Tempel 1. This bold mission design enables cometary researchers to peer into the cometary nucleus, analyzing the material excavated with its imagers and spectrometers. The book describes the mission, its objectives, expected results, payload, and data products in articles written by those most closely involved. This mission has the potential of revolutionizing our understanding of the cometary nucleus.

  2. Cerebello-cortical heterotopia in dentate nucleus, and other microdysgeneses in trisomy D1 (Patau) syndrome.

    Science.gov (United States)

    Hori, A; Peiffer, J; Pfeiffer, R A; Iizuka, R

    1980-01-01

    Several new histological findings in six cases of the trisomy D1 syndrome are described: hyperplasia of fetal structures (indusium griseum, median raphe of the medulla oblongata) and completely developed cerebellar cortical heterotopia in the dentate nucleus. In one case, a heterotopic pontine nucleus was found within the cerebellar white matter. The coexistence of overdeveloped and remaining fetal structures is emphasized. Several hypotheses regarding cerebellar dysgenesis are discussed.

  3. Effect of energy transfer from atomic electron shell to an α particle emitted by decaying nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Igashov, S. Yu., E-mail: igashov@theor.mephi.ru [All-Russian Research Institute of Automatics (Russian Federation); Tchuvil’sky, Yu. M. [Moscow State University, Skobeltsyn Institute of Nuclear Physics (Russian Federation)

    2016-12-15

    The process of energy transfer from the electron shell of an atom to an α particle propagating through the shell is formulated mathematically. Using the decay of the {sup 226}Ra nucleus as an example, it is demonstrated that this phenomenon increases the α-decay intensity in contrast with other known effects of similar type. Moreover, the α decay of the nucleus is more strongly affected by the energy transfer than by all other effects taken together.

  4. Comparison of Hi-C results using in-solution versus in-nucleus ligation.

    Science.gov (United States)

    Nagano, Takashi; Várnai, Csilla; Schoenfelder, Stefan; Javierre, Biola-Maria; Wingett, Steven W; Fraser, Peter

    2015-08-26

    Chromosome conformation capture and various derivative methods such as 4C, 5C and Hi-C have emerged as standard tools to analyze the three-dimensional organization of the genome in the nucleus. These methods employ ligation of diluted cross-linked chromatin complexes, intended to favor proximity-dependent, intra-complex ligation. During development of single-cell Hi-C, we devised an alternative Hi-C protocol with ligation in preserved nuclei rather than in solution. Here we directly compare Hi-C methods employing in-nucleus ligation with the standard in-solution ligation. We show in-nucleus ligation results in consistently lower levels of inter-chromosomal contacts. Through chromatin mixing experiments we show that a significantly large fraction of inter-chromosomal contacts are the result of spurious ligation events formed during in-solution ligation. In-nucleus ligation significantly reduces this source of experimental noise, and results in improved reproducibility between replicates. We also find that in-nucleus ligation eliminates restriction fragment length bias found with in-solution ligation. These improvements result in greater reproducibility of long-range intra-chromosomal and inter-chromosomal contacts, as well as enhanced detection of structural features such as topologically associated domain boundaries. We conclude that in-nucleus ligation captures chromatin interactions more consistently over a wider range of distances, and significantly reduces both experimental noise and bias. In-nucleus ligation creates higher quality Hi-C libraries while simplifying the experimental procedure. We suggest that the entire range of 3C applications are likely to show similar benefits from in-nucleus ligation.

  5. Delineation of motoneuron subgroups supplying individual eye muscles in the human oculomotor nucleus

    OpenAIRE

    Che Ngwa, Emmanuel; Zeeh, Christina; Messoudi, Ahmed; Büttner-Ennever, Jean A.; Horn, Anja K. E.

    2014-01-01

    The oculomotor nucleus (nIII) contains the motoneurons of medial, inferior, and superior recti (MR, IR, and SR), inferior oblique (IO), and levator palpebrae (LP) muscles. The delineation of motoneuron subgroups for each muscle is well-known in monkey, but not in human. We studied the transmitter inputs to human nIII and the trochlear nucleus (nIV), which innervates the superior oblique muscle (SO), to outline individual motoneuron subgroups. Parallel series of sections from human brainstems ...

  6. Identification of motoneurons innervating individual extraocular muscles within the oculomotor nucleus in human

    OpenAIRE

    Che Ngwa, Emmanuel

    2016-01-01

    Der Nucleus oculomotorius nIII und Nucleus trochlearis (nIV) im Mittelhirn enthalten die Motoneurone der extraoculären Augenmuskeln. Ziel der vorliegenden Arbeit war die Identifizierung der verschiedenen Motoneuronengruppen im humanen nIII und nIV, welche individuelle Augenmuskeln innervieren. Dies erfolgte anhand verschiedener histochemischer Färbungen, die im Vergleich zu Daten an Affen erhoben wurden. Der nIV innerviert nur den Musculus obliquus superior (SO), während nIII die Motoneurone ...

  7. Delineation of motoneuron subgroups supplying individual eye muscles in the human oculomotor nucleus

    OpenAIRE

    Emmanuel eChe-Ngwa; Christina eZeeh; Christina eZeeh; Ahmed eMessoudi; Jean Alice Büttner-Ennever; Anja Kerstin Ellen Horn; Anja Kerstin Ellen Horn

    2014-01-01

    The oculomotor nucleus (nIII) contains the motoneurons of medial, inferior and superior recti (MR, IR, SR), inferior oblique (IO) and levator palpebrae (LP) muscles. The delineation of motoneuron subgroups for each muscle is well-known in monkey, but not in human. We studied the transmitter inputs to human nIII and the trochlear nucleus (nIV), which innervates the superior oblique muscle (SO), to outline individual motoneuron subgroups. Parallel series of sections from human brainstems were i...

  8. Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS.

    Science.gov (United States)

    Purba, J S; Hofman, M A; Portegies, P; Troost, D; Swaab, D F

    1993-08-01

    The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age range 25-62 years), four of whom had a probable HIV-1 associated dementia complex, and six non-demented heterosexuals (four males and two females, age range 21-73 years). Ten males without a primary neurological or psychiatric disease served as a control group. The number of OXT-expressing neurons in the paraventricular nucleus of both groups of AIDS patients was approximately 40% lower than that of the controls. In contrast, the three groups showed no significant differences in the number of AVP-expressing neurons in the paraventricular nucleus. Since there were no significant differences in the number of AVP and OXT cells between the homosexual and heterosexual subjects with AIDS, the morphological difference in the paraventricular nucleus seems to be related to AIDS and not to sexual orientation. No inflammatory changes were found in the paraventricular nucleus area. The selective changes in the OXT neurons of the paraventricular nucleus may be the basis for part of the neuroendocrine, autonomic dysfunction or vegetative symptoms in AIDS.

  9. Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites.

    Science.gov (United States)

    Cohen, Michael S; Bas Orth, Carlos; Kim, Hyung Joon; Jeon, Noo Li; Jaffrey, Samie R

    2011-07-05

    Signaling from dendritic synapses to the nucleus regulates important aspects of neuronal function, including synaptic plasticity. The neurotrophin brain-derived neurotrophic factor (BDNF) can induce long-lasting strengthening of synapses in vivo and this effect is dependent on transcription. However, the mechanism of signaling to the nucleus is not well understood. Here we describe a microfluidic culture device to investigate dendrite-to-nucleus signaling. Using these microfluidic devices, we demonstrate that BDNF can act directly on dendrites to elicit an anterograde signal that induces transcription of the immediate early genes, Arc and c-Fos. Induction of Arc is dependent on dendrite- and cell body-derived calcium, whereas induction of c-Fos is calcium-independent. In contrast to retrograde neurotrophin-mediated axon-to-nucleus signaling, which is MEK5-dependent, BDNF-mediated anterograde dendrite-to-nucleus signaling is dependent on MEK1/2. Intriguingly, the activity of TrkB, the BDNF receptor, is required in the cell body for the induction of Arc and c-Fos mediated by dendritically applied BDNF. These results are consistent with the involvement of a signaling endosome-like pathway that conveys BDNF signals from the dendrite to the nucleus.

  10. Deiters' Nucleus. Its Role in Cerebellar Ideogenesis : The Ferdinando Rossi Memorial Lecture.

    Science.gov (United States)

    Voogd, Jan

    2016-02-01

    Otto Deiters (1834-1863) was a promising neuroscientist who, like Ferdinando Rossi, died too young. His notes and drawings were posthumously published by Max Schultze in the book "Untersuchungen über Gehirn und Rückenmark." The book is well-known for his dissections of nerve cells, showing the presence of multiple dendrites and a single axon. Deiters also made beautiful drawings of microscopical sections through the spinal cord and the brain stem, the latter showing the lateral vestibular nucleus which received his name. This nucleus, however, should be considered as a cerebellar nucleus because it receives Purkinje cell axons from the vermal B zone in its dorsal portion. Afferents from the labyrinth occur in its ventral part. The nucleus gives rise to the lateral vestibulospinal tract. The cerebellar B module of which Deiters' nucleus is the target nucleus was used in many innovative studies of the cerebellum on the zonal organization of the olivocerebellar projection, its somatotopical organization, its microzones, and its role in posture and movement that are the subject of this review.

  11. Subthalamic nucleus stimulation and levodopa modulate cardiovascular autonomic function in Parkinson's disease.

    Science.gov (United States)

    Li, Kai; Haase, Rocco; Rüdiger, Heinz; Reimann, Manja; Reichmann, Heinz; Wolz, Martin; Ziemssen, Tjalf

    2017-08-01

    We aimed to explore the effects of bilateral subthalamic nucleus stimulation and levodopa on cardiovascular autonomic function in Parkinson's disease. Twenty-six Parkinson's disease patients with bilateral subthalamic nucleus stimulation in a stable state were tested under stimulation off and dopaminergic medication off (OFF-OFF), stimulation on and dopaminergic medication off (ON-OFF), and stimulation on and medication (levodopa) on (ON-ON) conditions by recording continuously blood pressure, ECG, and respiration at rest, during metronomic deep breathing, and head-up tilt test. Thirteen patients were diagnosed as orthostatic hypotension by head-up tilt test. Baroreflex sensitivity and spectral analyses were performed by trigonometric regressive spectral analysis. Subthalamic nucleus stimulation and levodopa had multiple influences. (1) Systolic blood pressure during tilt-up was reduced by subthalamic nucleus stimulation, and then further by levodopa. (2) Subthalamic nucleus stimulation and levodopa had different effects on sympathetic and parasympathetic regulations in Parkinson's disease. (3) Levodopa decreased baroreflex sensitivity and RR interval only in the orthostatic hypotension group, and had opposite effects on the non-orthostatic hypotension group. These findings indicate that subthalamic nucleus stimulation and levodopa have different effects on cardiovascular autonomic function in Parkinson's disease, which are modulated by the presence of orthostatic hypotension as well.

  12. The Cell Nucleus in Physiological and Experimentally Induced Hypometabolism

    Science.gov (United States)

    Malatesta, M.

    The main problem for manned space mission is, at present, represented by the mass penalty associated to the human presence. An efficient approach could be the induction of a hypometabolic stasis in the astronauts, thus drastically reducing the physical and psychological requirements of the crew. On the other hand, in the wild, a reduction in resource consumptions physiologi- cally occurs in certain animals which periodically enter hibernation, a hypometabolic state in which both the energy need and energy offer are kept at a minimum. During the last twelve years, we have been studying different tissues of hibernating dormice, with the aim of analyzing their features during the euthermia -hibernation-arousal cycle as well as getting insight into the mechanisms allowing adaptation to hypometabolism. We paid particular attention to the cell nucleus, as it is the site of chief metabolic functions, such as DNA replication and RNA transcription. Our observations revealed no significant modification in the basic features of cell nuclei during hibernation; however, the cell nuclei of hibernating dormice showed unusual nuclear bodies containing molecules involved in RNA pathways. Therefore, we supposed that they could represent storage/assembly sites of several factors for processing some RNA which could be slowly synthesised during hibernation and rapidly and abundantly released in early arousal in order to meet the increased metabolic needs of the cell. The nucleolus also underwent structural and molecular modifications during hibernation, maybe to continue important nucleolar functions, or, alternatively, permit a most efficient reactivation upon arousal. On the basis of the observations made in vivo , we recently tried to experimentally induce a reversible hypometabolic state in in vitro models, using cell lines derived from hibernating and non-hibernating species. By administering the synthetic opioid DADLE, we could significantly reduce both RNA transcrip- tion and

  13. Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake.

    Science.gov (United States)

    Herisson, F M; Waas, J R; Fredriksson, R; Schiöth, H B; Levine, A S; Olszewski, P K

    2016-04-01

    Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting. © 2016

  14. Chaos and Regularity in the Doubly Magic Nucleus 208Pb

    Science.gov (United States)

    Dietz, B.; Heusler, A.; Maier, K. H.; Richter, A.; Brown, B. A.

    2017-01-01

    High-resolution experiments have recently lead to a complete identification (energy, spin, and parity) of 151 nuclear levels up to an excitation energy of Ex=6.20 MeV in 208Pb [Heusler et al., Phys. Rev. C 93, 054321 (2016), 10.1103/PhysRevC.93.054321]. We present a thorough study of the fluctuation properties in the energy spectra of the unprecedented set of nuclear bound states. In a first approach, we group states with the same spin and parity into 14 subspectra, analyze standard statistical measures for short- and long-range correlations, i.e., the nearest-neighbor spacing distribution, the number variance Σ2, the Dyson-Mehta Δ3 statistics, and the novel distribution of the ratios of consecutive spacings of adjacent energy levels in each energy sequence, and then compute their ensemble average. Their comparison with a random matrix ensemble which interpolates between Poisson statistics expected for regular systems and the Gaussian orthogonal ensemble (GOE) predicted for chaotic systems shows that the data are well described by the GOE. In a second approach, following an idea of Rosenzweig and Porter [Phys. Rev. 120, 1698 (1960), 10.1103/PhysRev.120.1698], we consider the complete spectrum composed of the independent subspectra. We analyze their fluctuation properties using the method of Bayesian inference involving a quantitative measure, called the chaoticity parameter f , which also interpolates between Poisson (f =0 ) and GOE statistics (f =1 ). It turns out to be f ≈0.9 . This is so far the closest agreement with a GOE observed in the spectra of bound states in a nucleus. The same analysis is also performed with spectra computed on the basis of shell model calculations with different interactions (surface-delta interaction, Kuo-Brown, Michigan-three-Yukawa). While the simple surface-delta interaction exhibits features typical for nuclear many-body systems with regular dynamics, the other, more realistic interactions yield chaoticity parameters f close

  15. Deep brain stimulation of the nucleus accumbens and bed nucleus of stria terminalis for obsessive-compulsive disorder: a case series.

    Science.gov (United States)

    Islam, Lucrezia; Franzini, Angelo; Messina, Giuseppe; Scarone, Silvio; Gambini, Orsola

    2015-04-01

    Obsessive-compulsive disorder (OCD) is a psychiatric condition defined by the presence of obsessions, compulsions, or both. It has a lifetime prevalence of 2%-3% and causes significant impairment in social and work functioning, as well as a reduced quality of life. Treatment includes pharmacotherapy and psychotherapy, but a significant number of patients fail to respond to treatment. Deep brain stimulation has shown to be a safe and effective procedure for severe, chronic, treatment-resistant OCD, and several surgical targets have been proposed for treatment, including the nucleus accumbens, the anterior limb of the internal capsule, the subthalamic nucleus, the globus pallidus, and the bed nucleus of stria terminalis. To report the first Italian case series of patients who underwent DBS of 2 distinct targets for OCD: nulceus accumbens and bed nulceus of stria terminalis. Four patients underwent DBS of the nulceus accumbens, and 4 patients underwent DBS of the bed nucleus of stria terminalis. Six patients showed a significant improvement in OCD symptoms. DBS of these 2 structures is a safe and effective procedure for the treatment of severe, refractory OCD. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Role of nucleus accumbens glutamatergic plasticity in drug addiction

    Directory of Open Access Journals (Sweden)

    Quintero GC

    2013-09-01

    Full Text Available Gabriel C Quintero1–31Florida State University – Panama, Clayton, Panama; 2Medical University of South Carolina, Charleston, South Carolina, USA; 3Smithsonian Tropical Research Institute, Ancon, Republic of PanamaAbstract: Substance dependence is characterized by a group of symptoms, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR. These symptoms include tolerance, withdrawal, drug consumption for alleviating withdrawal, exaggerated consumption beyond original intention, failure to reduce drug consumption, expending a considerable amount of time obtaining or recovering from the substance’s effects, disregard of basic aspects of life (for example, family, and maintenance of drug consumption, despite facing adverse consequences. The nucleus accumbens (NAc is a brain structure located in the basal forebrain of vertebrates, and it has been the target of addictive drugs. Different neurotransmitter systems at the level of the NAc circuitry have been linked to the different problems of drug addiction, like compulsive use and relapse. The glutamate system has been linked mainly to relapse after drug-seeking extinction. The dopamine system has been linked mainly to compulsive drug use. The glutamate homeostasis hypothesis centers around the dynamics of synaptic and extrasynaptic levels of glutamate, and their impact on circuitry from the prefrontal cortex (PFC to the NAc. After repetitive drug use, deregulation of this homeostasis increases the release of glutamate from the PFC to the NAc during drug relapse. Glial cells also play a fundamental role in this hypothesis; glial cells shape the interactions between the PFC and the NAc by means of altering glutamate levels in synaptic and extrasynaptic spaces. On the other hand, cocaine self-administration and withdrawal increases the surface expression of subunit glutamate receptor 1 (GluA1 of alpha-amino-3-hydroxy-5-methyl-4

  17. The Nucleus of Comet 67P/Churyumov-Gerasimenko: Lots of Surprises

    Science.gov (United States)

    Weissman, Paul R.; Rosetta Science Working Team

    2016-10-01

    ESA's Rosetta mission has made many new and unexpected discoveries since its arrival at comet 67P/Churyumov-Gerasimenko in August 2014. The first of these was the unusual shape of the cometary nucleus. Although bilobate nuclei had been seen before, the extreme concavities on 67P were unexpected. Evidence gathered during the mission suggests that two independent bodies came together to form 67P, rather than the nucleus being a single body that was sculpted by sublimation and/or other processes. Although not a surprise, early observations showed that the nucleus rotation period had decreased by ~22 minutes since the previous aphelion passage. A similar rotation period decrease was seen post-perihelion during the encounter. These changes likely arise from asymmetric jetting forces from the irregular nucleus. Initially, Rosetta's instruments found little evidence for water ice on the surface; the presence of surface water ice increased substantially as the nucleus approached perihelion. The nucleus bulk density, 533 ± 6 kg/m3, was measured with Radio Science and OSIRIS imaging of the nucleus volume. This confirmed previous estimates based on indirect methods that the bulk density of cometary nuclei was on the order of 500-600 kg/m3 and on measurement of the density of 9P/Tempel 1's nucleus by Deep Impact. Nucleus topography proved to be highly varied, from smooth dust-covered plains to shallow circular basins, to the very rough terrain where the Philae lander came to rest. Evidence of thermal cracking is everywhere. The discovery of cylindrical pits on the surface, typically 100-200m in diameter with similar depths was a major surprise and has been interpreted as sinkholes. "Goose-bump" terrain consisting of apparently random piles of boulders 2-3 m in diameter was another unexpected discovery. Apparent layering with scales of meters to many tens of meters was seen but there was little or no evidence for impact features. Radar tomography of the interior of the "head

  18. Immunohistochemical localization of ionotropic glutamate receptors in the rat red nucleus.

    Science.gov (United States)

    Minbay, Zehra; Serter Kocoglu, Sema; Gok Yurtseven, Duygu; Eyigor, Ozhan

    2017-02-21

    In this study, we aimed to determine the presence as well as the diverse distribution of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor subunits in the rat red nucleus. Using adult Sprague-Dawley rats as the experimental animals, immunohistochemistry was performed on 30 µm thick coronal brain sections with antibodies against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (GluA1-4), kainate (GluK1, GluK2/3, and GluK5), and NMDA (GluN1 and GluN2A) receptor subunits. The results showed that all ionotropic glutamate receptor subunits are expressed in the red nucleus. Specific staining was localized in the neuron bodies and processes. However, the pattern of immunoreactivity and the number of labeled neurons changed depending on the type of ionotropic glutamate receptor subunits and the localization of neurons in the red nucleus. The neurons localized in the magnocellular part of the red nucleus were particularly immunopositive for GluA2, GluA4, GluK2/3, GluK5, GluN1, and GluN2A receptor proteins. In the parvocellular part of the red nucleus, ionotropic glutamate receptor subunit immunoreactivity of variable intensity (lightly to moderately stained) was detected in the neurons. These results suggest that red nucleus neurons in rat heterogeneously express ionotropic glutamate receptor subunits to form functional receptor channels. In addition, the likelihood of the coexpression of different subunits in the same subgroup of neurons suggests the formation of receptor channels with diverse structure by way of different subunit combination, and the possibility of various neuronal functions through these channels in the red nucleus.

  19. Kinds of nucleus for effective pearl cultivation of the pearl oysters, Pinctada fucata

    Directory of Open Access Journals (Sweden)

    Kanjanachatree, K.

    2007-07-01

    Full Text Available Seeding is the most important aspect of pearl cultivation, and appropriate nucleus can determine the quality of a pearl : nacre secretion and accumulation around the nucleus. This affects harvest time, nucleus extrusion, survival rate of the pearl oysters and the production cost. In order to provide nuclei to substitute for those imported from China which are made from freshwater pearl oyster-shells, 3 kinds of the local shells of Pinctada fucata, Pteria penguin and Pinctada maxima were selected for seed production. The obtained nuclei have various diameters depend on the shell width at the hinge region. The average diameters are 5.44, 6.78, 7.54 and 6.10 mm, while their production costs are 5, 7.7, 18.5 and 7.5 baht per 1 nucleus, respectively, for Pinctada fucata, Pteria penguin, Pinctada maxima and freshwater pearl oysters (control group. After nucleus implantation into the gonad of culture pearl oysters, Pinctada fucata, and rearing in the sea, the obtained pearls using nuclei made from the shells of Pinctada fucata and Pinctada maxima (both belong to the same genus as the implanted culture pearl oysters have as good nacre formation as that from freshwater pearl oysters. In contrast, the pearl production using nuclei made from Pteria penguin-shells have significantly worse nacre formation. Survival rate of the culture oysters seeded with nuclei made from Pinctada fucata-shells is highest at 47%, nucleus extrusion 8% only, and harvest rate 31%; while with Pinctada maxima-shells, these values are 38%, 17.5% and 14%, respectively. So the nuclei made from local Pinctada fucata-shells are appropriate for pearl cultivation and are comparable to imported nuclei. Although the obtained pearls are small, the nuclei made from Pinctada fucata-shells have low cost, low nucleus extrusion and high productivity.

  20. Distribution of Calretinin Immunoreactivity in the Lateral Nucleus of the Bottlenose Dolphin (Tursiops truncatus) Amygdala.

    Science.gov (United States)

    Rambaldi, A M; Cozzi, B; Grandis, A; Canova, M; Mazzoni, M; Bombardi, C

    2017-11-01

    The amgdaloid complex consists of different nuclei, each with unique cytoarchitectonic, chemoarchitectonic and connectional characteristics. Most of the inputs coming from cortical and subcortical areas enter the amygdala via the lateral nucleus, which makes it the main receiving structure of the complex. The activity of its neurons is coordinated and modulated by different inhibitory, GABAergic-interneurons, which can be classified for their expression of various calcium-binding proteins, as well as by morphological characteristics. This research based on the analysis of the amygdala of three bottlenose dolphins, provides the first description of the topography, cytoarchitecture and distribution of calretinin immunoreactivity of the lateral nucleus. Our observations on the bottlenose dolphin confirmed the general topography of the mammalian amygdala and of the lateral nucleus. Notably, we identified six subdivision of the nucleus, more than those reported until now in the rat, monkey and human lateral nucleus. This could reveal an outstanding capability of integration and elaboration of external stimuli. In addition, we observed a strong presence of CR-immunoreactive (-ir) neurons and fibres. CR-ir neurons were mainly non-pyramidal inhibitory neurons; in particular, 80% of IR-cells were represented by large and small polygonal neurons. In the lateral nucleus of the human amygdala, CR-ir neurons form inhibitory synapses on calbindin-D28k-IR inhibitory interneurons. Since calbindin-D28k-ir interneurons make inhibitory synapses on the pyramidal cells, the final goal of the CR-ir interneurons could be the synchronization of cells activity, thus playing an important role in the control of information flow in the lateral amygdalar nucleus. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2008-2016, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Twitch and nontwitch motoneuron subgroups in the oculomotor nucleus of monkeys receive different afferent projections.

    Science.gov (United States)

    Wasicky, Richard; Horn, Anja K E; Büttner-Ennever, Jean A

    2004-11-08

    Motoneurons in the primate oculomotor nucleus can be divided into two categories, those supplying twitch muscle fibers and those supplying nontwitch muscle fibers. Recent studies have shown that twitch motoneurons lie within the classical oculomotor nucleus (nIII), and nontwitch motoneurons lie around the borders. Nontwitch motoneurons of medial and inferior rectus are in the C group dorsomedial to nIII, whereas those of inferior oblique and superior rectus lie near the midline are in the S group. In this anatomical study, afferents to the twitch and nontwitch subgroups of nIII have been anterogradely labeled by injections of tritiated leucine into three areas and compared. 1) Abducens nucleus injections gave rise to silver grain deposits over all medial rectus subgroups, both twitch and nontwitch. 2) Laterally placed vestibular complex injections that included the central superior vestibular nucleus labeled projections only in twitch motoneuron subgroups. However, injections into the parvocellular medial vestibular nucleus (mvp), or Y group, resulted in labeled terminals over both twitch and nontwitch motoneurons. 3) Pretectal injections that included the nucleus of the optic tract (NOT), and the olivary pretectal nucleus (OLN), labeled terminals only over nontwitch motoneurons, in the contralateral C group and in the S group. Our study demonstrates that twitch and nontwitch motoneuron subgroups do not receive identical afferent inputs. They can be controlled either in parallel, or independently, suggesting that they have basically different functions. We propose that twitch motoneurons primarily drive eye movements and nontwitch motoneurons the tonic muscle activity, as in gaze holding and vergence, possibly involving a proprioceptive feedback system. 2004 Wiley-Liss, Inc.

  2. Role of nucleus accumbens glutamatergic plasticity in drug addiction.

    Science.gov (United States)

    Quintero, Gabriel C

    2013-01-01

    Substance dependence is characterized by a group of symptoms, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). These symptoms include tolerance, withdrawal, drug consumption for alleviating withdrawal, exaggerated consumption beyond original intention, failure to reduce drug consumption, expending a considerable amount of time obtaining or recovering from the substance's effects, disregard of basic aspects of life (for example, family), and maintenance of drug consumption, despite facing adverse consequences. The nucleus accumbens (NAc) is a brain structure located in the basal forebrain of vertebrates, and it has been the target of addictive drugs. Different neurotransmitter systems at the level of the NAc circuitry have been linked to the different problems of drug addiction, like compulsive use and relapse. The glutamate system has been linked mainly to relapse after drug-seeking extinction. The dopamine system has been linked mainly to compulsive drug use. The glutamate homeostasis hypothesis centers around the dynamics of synaptic and extrasynaptic levels of glutamate, and their impact on circuitry from the prefrontal cortex (PFC) to the NAc. After repetitive drug use, deregulation of this homeostasis increases the release of glutamate from the PFC to the NAc during drug relapse. Glial cells also play a fundamental role in this hypothesis; glial cells shape the interactions between the PFC and the NAc by means of altering glutamate levels in synaptic and extrasynaptic spaces. On the other hand, cocaine self-administration and withdrawal increases the surface expression of subunit glutamate receptor 1 (GluA1) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors at the level of the NAc. Also, cocaine self-administration and withdrawal induce the formation of subunit glutamate receptor 2 (GluA2), lacking the Ca(2+)-permeable AMPA receptors (CP-AMPARs) at the level of the NAc

  3. Ab initio calculation of the potential bubble nucleus 34Si

    Science.gov (United States)

    Duguet, T.; Somà, V.; Lecluse, S.; Barbieri, C.; Navrátil, P.

    2017-03-01

    Background: The possibility that an unconventional depletion (referred to as a "bubble") occurs in the center of the charge density distribution of certain nuclei due to a purely quantum mechanical effect has attracted theoretical and experimental attention in recent years. Based on a mean-field rationale, a correlation between the occurrence of such a semibubble and an anomalously weak splitting between low angular-momentum spin-orbit partners has been further conjectured. Energy density functional and valence-space shell model calculations have been performed to identify and characterize the best candidates, among which 34Si appears as a particularly interesting case. While the experimental determination of the charge density distribution of the unstable 34Si is currently out of reach, (d ,p ) experiments on this nucleus have been performed recently to test the correlation between the presence of a bubble and an anomalously weak 1 /2--3 /2- splitting in the spectrum of 35Si as compared to 37S. Purpose: We study the potential bubble structure of 34Si on the basis of the state-of-the-art ab initio self-consistent Green's function many-body method. Methods: We perform the first ab initio calculations of 34Si and 36S. In addition to binding energies, the first observables of interest are the charge density distribution and the charge root-mean-square radius for which experimental data exist in 36S. The next observable of interest is the low-lying spectroscopy of 35Si and 37S obtained from (d ,p ) experiments along with the spectroscopy of 33Al and 35P obtained from knock-out experiments. The interpretation in terms of the evolution of the underlying shell structure is also provided. The study is repeated using several chiral effective field theory Hamiltonians as a way to test the robustness of the results with respect to input internucleon interactions. The convergence of the results with respect to the truncation of the many-body expansion, i.e., with respect to

  4. Comparison of ozil and traditional phacoemulsification mode in different grade nucleus cataract

    Directory of Open Access Journals (Sweden)

    Feng Gao

    2015-07-01

    Full Text Available AIM: To evaluate the application of phacoemulsification of different nucleus density using ozil and traditional mode. METHODS: A total of 89 eyes(72 patients(visual acuity was of 0.6 and above after 1mo follow-upof different nucleus density level(LOCS Ⅱ criteria grade Ⅲ 46 eyes, grade Ⅳ and more 43 eyeswere randomly assigned into 2 groups: ozil group(group A, grade Ⅲ 22 eyes(torsional energy 80% IP on; grade Ⅳ and more 17 eyes(torsional energy 100% IP on; Traditional mode group(group B, grade Ⅲ 24 eyes(energy 50%, grade Ⅳ and more 26 eyes(energy 60%~70%. All surgeries were performed by the same experienced surgeon,who use the chop to split the nucleus in the application of phacoemulsification. Intraoperative parameters were total equivalent pawer(TEP, cumulative dissipated energy(CDEand effective phaco time(EPTand surgical complications. The effectiveness of the two modes in dealing with hard-core cataract phacoemulsification were compared.RESULTS: GradeⅢ nucleus dealing: TEP of ozil group was significantly higher than that of the traditional mode group \\〖(24.58±7.78% vs(13.84±1.97%\\〗and EPT of ozil group was significantly lower than that of the traditional mode group(50.59±14.73 s vs 60.19±9.04 s, Pvs(13.38±2.85\\〗. Grade Ⅳ and more nucleus dealing: CDE \\〖(34.10±13.48%\\〗 and EPT(104.64±32.4sof the ozil group was higher than CDE \\〖(30.31±13.48%\\〗 and EPT(93.01±41.01sof the traditional mode group, but there were no difference between two groups. Obstacles in the needle of phacoemulsification surgery: ozil group 4/17, traditional mode group 2/26(χ2=2.16, P=0.14.CONCLUSION: Bothozil and traditional mode can deal with all kinds of nucleus effectively and safely. Ozil mode is more efficacy and quick deal in grade Ⅲ nucleus. With the increase of nucleus hardness, the traditional mode still have the advantage of high efficiency and no obstacle to dealing patients with grade Ⅳ and more nucleus

  5. Toward a cancer therapy with boron-rich oligomeric phosphate diesters that target the cell nucleus

    Science.gov (United States)

    Nakanishi, Akira; Guan, Lufeng; Kane, Robert R.; Kasamatsu, Harumi; Hawthorne, M. Frederick

    1999-01-01

    The viability of boron neutron capture therapy depends on the development of tumor-targeting agents that contain large numbers of boron-10 (10B) atoms and are readily taken up by cells. Here we report on the selective uptake of homogeneous fluorescein-labeled nido-carboranyl oligomeric phosphate diesters (nido-OPDs) by the cell nucleus and their long-term retention after their delivery into the cytoplasm of TC7 cells by microinjection. All nido-OPDs accumulated in the cell nucleus within 2 h after microinjection. However, nido-OPDs in which the carborane cage was located on a side chain attached to the oligomeric backbone were redistributed between both the cytoplasm and nucleus after 24 h of incubation, whereas nido-OPDs in which the carborane cage was located along the oligomeric backbone remained primarily in the nucleus. Furthermore, cell-free incubation of digitonin-permeabilized TC7 cells with the nido-OPDs resulted in nuclear accumulation of the compounds, thus corroborating the microinjection studies. Our observation of fluorescence primarily located in the cell nucleus indicates that nuclear-specific uptake of sufficient amounts of 10B for effective boron neutron capture therapy (≈108–109 10B atoms/tumor cell) via nido-OPDs is achievable. PMID:9874802

  6. η-nucleus interaction from the d + d reaction around the η production threshold

    Energy Technology Data Exchange (ETDEWEB)

    Ikeno, N. [Tottori University, Department of Life and Environmental Agricultural Sciences, Tottori (Japan); Nagahiro, H. [Nara Women' s University, Department of Physics, Nara (Japan); Osaka University, Research Center for Nuclear Physics (RCNP), Ibaraki (Japan); Jido, D. [Tokyo Metropolitan University, Department of Physics, Hachioji (Japan); Hirenzaki, S. [Nara Women' s University, Department of Physics, Nara (Japan)

    2017-10-15

    The η mesic nucleus is considered to be one of the interesting exotic many-body systems and has been studied since the 1980s theoretically and experimentally. Recently, the formation of the η mesic nucleus in the fusion reactions of the light nuclei such as d + d → (η + α) → X has been proposed and the experiments have been performed by WASA-at-COSY. We develop a theoretical model to evaluate the formation rate of the η mesic nucleus in the fusion reactions and show the calculated results. We find that the η bound states could be observed in the reactions in cases with the strong attractive and small absorptive η-nucleus interactions. We compare our results with existing data of the d + d → η + α and the d + d → {sup 3}He + N + π reactions. We find that the analyses by our theoretical model with the existing data can provide new information on the η-nucleus interaction. (orig.)

  7. Neuroelectric signatures of reward learning and decision-making in the human nucleus accumbens.

    Science.gov (United States)

    Cohen, Michael X; Axmacher, Nikolai; Lenartz, Doris; Elger, Christian E; Sturm, Volker; Schlaepfer, Thomas E

    2009-06-01

    Learning that certain actions lead to risky rewards is critical for biological, social, and economic survival, but the precise neural mechanisms of such reward-guided learning remain unclear. Here, we show that the human nucleus accumbens plays a key role in learning about risks by representing reward value. We recorded electrophysiological activity directly from the nucleus accumbens of five patients undergoing deep brain stimulation for treatment of refractory major depression. Patients engaged in a simple reward-learning task in which they first learned stimulus-outcome associations (learning task), and then were able to choose from among the learned stimuli (choosing task). During the learning task, nucleus accumbens activity reflected potential and received reward values both during the cue stimulus and during the feedback. During the choosing task, there was no nucleus accumbens activity during the cue stimulus, but feedback-related activity was pronounced and similar to that during the learning task. This pattern of results is inconsistent with a prediction error response. Finally, analyses of cross-correlations between the accumbens and simultaneous recordings of medial frontal cortex suggest a dynamic interaction between these structures. The high spatial and temporal resolution of these recordings provides novel insights into the timing of activity in the human nucleus accumbens, its functions during reward-guided learning and decision-making, and its interactions with medial frontal cortex.

  8. Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant death

    Science.gov (United States)

    Lavezzi, Anna M.; Matturri, Luigi

    2012-01-01

    This study expands our understanding of the organization of the human caudal pons, providing a morphologic characterization of the medial superior olivary nucleus (MSO), component of the superior olivary complex (SOC) that plays an important role in the processing of acoustic information. We examined victims of sudden unexplained fetal and infant death and controls (n = 75), from 25 gestational weeks to 8 months of postnatal age, by complete autopsy and in-depth autonomic nervous system histological examination, particularly of the MSO nucleus, the focus of this study. Peculiar cytoarchitectural features of the MSO nucleus were found in sudden death cases, such as hypoplasia/agenesis and immature hypercellularity, frequently related to dysgenesis of contiguous structures involved in respiratory rhythm-generating circuit, in particular to hypoplasia of the retrotrapezoid and the facial nuclei. We propose the involvement of this nucleus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities. Besides, we highlight the fundamental role of the maternal smoking in pregnancy as etiological factor in the dysmorphic neuroanatomical development of the MSO nucleus. PMID:23205011

  9. DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected?

    Science.gov (United States)

    Noblanc, Anais; Damon-Soubeyrand, Christelle; Karrich, Bouchta; Henry-Berger, Joelle; Cadet, Rémi; Saez, Fabrice; Guiton, Rachel; Janny, Laurent; Pons-Rejraji, Hanae; Alvarez, Juan G; Drevet, Joël R; Kocer, Ayhan

    2013-12-01

    Gamete DNA integrity is one key parameter conditioning reproductive success as well as the quality of life for the offspring. In particular, damage to the male nucleus can have profound negative effects on the outcome of fertilization. Because of the absence of repair activity of the quiescent mature spermatozoa it is easily subjected to nuclear damage, of which oxidative damage is by far the most prominent. In relation to the organization of the mammalian sperm nucleus we show here that one can correlate the nuclear regions of lower compaction with areas preferentially showing oxidative damage. More precisely, we show that oxidative DNA damage targets primarily histone-rich and nuclear matrix-attached domains located in the peripheral and basal regions of the mouse sperm nucleus. These particular sperm DNA domains were recently shown to be enriched in genes of paramount importance in postfertilization DNA replication events and in the onset of the embryonic developmental program. We propose that monitoring of sperm DNA oxidation using the type of assay presented here should be considered in clinical practice when one wants to estimate the integrity of the paternal nucleus along with more classical assays that essentially analyze DNA fragmentation and nucleus compaction. © 2013 Elsevier Inc. All rights reserved.

  10. Shape and Size of the Fission Yeast Nucleus are governed by Equilibrium Mechanics

    Science.gov (United States)

    Lim, Gerald; Huber, Greg; Miller, Jonathan; Sazer, Shelley

    2006-03-01

    Nuclear morphogenesis in the asexual reproduction of Schizosaccharomyces pombe (fission yeast) consists of two stages: (i) volume-doubling growth, in which a round nucleus inflates uniformly, and (ii) division, in which the nucleus undergoes shape changes from round to oblong to peanut to dumbbell before it resolves into two smaller, round daughter nuclei, driven by the formation and elongation of a microtubule-based spindle within the nucleus. The combined volume of the daughter nuclei immediately after division is the same as the volume of the single nucleus at the onset of division. Consequently, the nuclear envelope (NE) area must increase by 26% during division. We are developing a model in order to determine the mechanics governing these shape and size changes. It is based on current knowledge of the nuclear structure, insight from normal and abnormal nuclei, and concepts from the mechanics governing lipid-bilayer membranes. We predict that (a) the NE prefers to be flat, (b) the NE is under tension, (c) the nucleus has an internal pressure, (d) nuclear growth is governed by the Law of Laplace, and (e) some abnormal nuclei behave like vesicles with encapsulated microtubules.

  11. Different discharge properties of facial nucleus motoneurons following neurotmesis in a rat model.

    Science.gov (United States)

    Shi, Suming; Xu, Lei; Li, Jianfeng; Han, Yuechen; Wang, Haibo

    2016-08-26

    Facial nucleus motoneurons innervating the facial expressive muscles are involved in a wide range of motor activities, however, the types of movement related neurons and their electrophysiological transformation after peripheral facial nerve injury haven't been revealed. This study was designed to elucidate the types of facial nucleus motoneurons and their alterations of discharge parameters following peripheral facial nerve injury in vivo. Here we set up a rat model by implanting electrode arrays into the brainstem and recorded the electrophysiological signals of facial nucleus neurons in the intact rats for 5 days, then transected the trunk of facial nerve (TF), and continued the record for 4 weeks. At the 4th week post-surgery, the morphological changes of TFs were analyzed. In this paper, we described two types of putative facial nucleus motoneurons based on their electrophysiological properties and their firing frequency adaptation. Type I motoneurons (n=57.6%) were characterized by a sustained spike adaptation, Type II motoneurons (n=26.2%) were identified by a phasic fast spike firing. Facial palsy and synkinesia, caused by neurotmesis of TF, were accompanied by firing rates reduction and firing pattern alteration of motoneurons. Our findings suggest the presence of two types of facial nucleus motorneurons, and their response patterns after neurotmesis support the notion that the discharge pattern of motorneurons may play an important role in the facial nerve function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. η-nucleus interaction from the d + d reaction around the η production threshold

    Science.gov (United States)

    Ikeno, N.; Nagahiro, H.; Jido, D.; Hirenzaki, S.

    2017-10-01

    The η mesic nucleus is considered to be one of the interesting exotic many-body systems and has been studied since the 1980s theoretically and experimentally. Recently, the formation of the η mesic nucleus in the fusion reactions of the light nuclei such as d + d → (η + α) → X has been proposed and the experiments have been performed by WASA-at-COSY. We develop a theoretical model to evaluate the formation rate of the η mesic nucleus in the fusion reactions and show the calculated results. We find that the η bound states could be observed in the reactions in cases with the strong attractive and small absorptive η-nucleus interactions. We compare our results with existing data of the d + d → η + α and the d + d → {}3He + N + π reactions. We find that the analyses by our theoretical model with the existing data can provide new information on the η-nucleus interaction.

  13. ΔJunD overexpression in the nucleus accumbens prevents sexual reward in female Syrian hamsters.

    Science.gov (United States)

    Been, L E; Hedges, V L; Vialou, V; Nestler, E J; Meisel, R L

    2013-08-01

    Motivated behaviors, including sexual experience, activate the mesolimbic dopamine system and produce long-lasting molecular and structural changes in the nucleus accumbens. The transcription factor ΔFosB is hypothesized to partly mediate this experience-dependent plasticity. Previous research in our laboratory has demonstrated that overexpressing ΔFosB in the nucleus accumbens of female Syrian hamsters augments the ability of sexual experience to cause the formation of a conditioned place preference. It is unknown, however, whether ΔFosB-mediated transcription in the nucleus accumbens is required for the behavioral consequences of sexual reward. We therefore used an adeno-associated virus to overexpress ΔJunD, a dominant negative binding partner of ΔFosB that decreases ΔFosB-mediated transcription by competitively heterodimerizing with ΔFosB before binding at promotor regions on target genes, in the nucleus accumbens. We found that overexpression of ΔJunD prevented the formation of a conditioned place preference following repeated sexual experiences. These data, when coupled with our previous findings, suggest that ΔFosB is both necessary and sufficient for behavioral plasticity following sexual experience. Furthermore, these results contribute to an important and growing body of literature demonstrating the necessity of endogenous ΔFosB expression in the nucleus accumbens for adaptive responding to naturally rewarding stimuli. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  14. Vestibular nucleus neurons respond to hindlimb movement in the decerebrate cat.

    Science.gov (United States)

    Arshian, Milad S; Hobson, Candace E; Catanzaro, Michael F; Miller, Daniel J; Puterbaugh, Sonya R; Cotter, Lucy A; Yates, Bill J; McCall, Andrew A

    2014-06-15

    The vestibular nuclei integrate information from vestibular and proprioceptive afferents, which presumably facilitates the maintenance of stable balance and posture. However, little is currently known about the processing of sensory signals from the limbs by vestibular nucleus neurons. This study tested the hypothesis that limb movement is encoded by vestibular nucleus neurons and described the changes in activity of these neurons elicited by limb extension and flexion. In decerebrate cats, we recorded the activity of 70 vestibular nucleus neurons whose activity was modulated by limb movements. Most of these neurons (57/70, 81.4%) encoded information about the direction of hindlimb movement, while the remaining neurons (13/70, 18.6%) encoded the presence of hindlimb movement without signaling the direction of movement. The activity of many vestibular nucleus neurons that responded to limb movement was also modulated by rotating the animal's body in vertical planes, suggesting that the neurons integrated hindlimb and labyrinthine inputs. Neurons whose firing rate increased during ipsilateral ear-down roll rotations tended to be excited by hindlimb flexion, whereas neurons whose firing rate increased during contralateral ear-down tilts were excited by hindlimb extension. These observations suggest that there is a purposeful mapping of hindlimb inputs onto vestibular nucleus neurons, such that integration of hindlimb and labyrinthine inputs to the neurons is functionally relevant. Copyright © 2014 the American Physiological Society.

  15. Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum.

    Science.gov (United States)

    Echevarría, Wihelma; Leite, M Fatima; Guerra, Mateus T; Zipfel, Warren R; Nathanson, Michael H

    2003-05-01

    Calcium is a second messenger in virtually all cells and tissues. Calcium signals in the nucleus have effects on gene transcription and cell growth that are distinct from those of cytosolic calcium signals; however, it is unknown how nuclear calcium signals are regulated. Here we identify a reticular network of nuclear calcium stores that is continuous with the endoplasmic reticulum and the nuclear envelope. This network expresses inositol 1,4,5-trisphosphate (InsP3) receptors, and the nuclear component of InsP3-mediated calcium signals begins in its locality. Stimulation of these receptors with a little InsP3 results in small calcium signals that are initiated in this region of the nucleus. Localized release of calcium in the nucleus causes nuclear protein kinase C (PKC) to translocate to the region of the nuclear envelope, whereas release of calcium in the cytosol induces translocation of cytosolic PKC to the plasma membrane. Our findings show that the nucleus contains a nucleoplasmic reticulum with the capacity to regulate calcium signals in localized subnuclear regions. The presence of such machinery provides a potential mechanism by which calcium can simultaneously regulate many independent processes in the nucleus.

  16. Enucleated cells reveal differential roles of the nucleus in cell migration, polarity, and mechanotransduction.

    Science.gov (United States)

    Graham, David M; Andersen, Tomas; Sharek, Lisa; Uzer, Gunes; Rothenberg, Katheryn; Hoffman, Brenton D; Rubin, Janet; Balland, Martial; Bear, James E; Burridge, Keith

    2018-01-19

    The nucleus has long been postulated to play a critical physical role during cell polarization and migration, but that role has not been defined or rigorously tested. Here, we enucleated cells to test the physical necessity of the nucleus during cell polarization and directed migration. Using enucleated mammalian cells (cytoplasts), we found that polarity establishment and cell migration in one dimension (1D) and two dimensions (2D) occur without the nucleus. Cytoplasts directionally migrate toward soluble (chemotaxis) and surface-bound (haptotaxis) extracellular cues and migrate collectively in scratch-wound assays. Consistent with previous studies, migration in 3D environments was dependent on the nucleus. In part, this likely reflects the decreased force exerted by cytoplasts on mechanically compliant substrates. This response is mimicked both in cells with nucleocytoskeletal defects and upon inhibition of actomyosin-based contractility. Together, our observations reveal that the nucleus is dispensable for polarization and migration in 1D and 2D but critical for proper cell mechanical responses. © 2018 Graham et al.

  17. A case of musical preference for Johnny Cash following deep brain stimulation of the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Mariska eMantione

    2014-05-01

    Full Text Available Music is among all cultures an important part of the live of most people. Music has psychological benefits and may generate strong emotional and physiological responses. Recently, neuroscientists have discovered that music influences the reward circuit of the nucleus accumbens, even when no explicit reward is present. In this clinical case study, we describe a 60-year old patient who developed a sudden and distinct musical preference for Johnny Cash following deep brain stimulation targeted at the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. This case report substantiates the assumption that the nucleus accumbens is involved in musical preference, based on the observation of direct stimulation of the accumbens with deep brain stimulation. It also shows that accumbens DBS can change musical preference without habituation of its rewarding properties.

  18. THE NUCLEUS OF MAIN-BELT COMET 259P/GARRADD

    Energy Technology Data Exchange (ETDEWEB)

    MacLennan, Eric M.; Hsieh, Henry H., E-mail: hsieh@ifa.hawaii.edu, E-mail: emaclenn@utk.edu [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States)

    2012-10-10

    We present observations of the main-belt comet 259P/Garradd, previously known as P/2008 R1 (Garradd), obtained in 2011 and 2012 using the Gemini North Telescope on Mauna Kea in Hawaii and the SOAR telescope at Cerro Pachon in Chile, with the goal of computing the object's phase function and nucleus size. We find an absolute magnitude of H{sub R} = 19.71 {+-} 0.05 mag and slope parameter of G{sub R} = -0.08 {+-} 0.05 for the inactive nucleus, corresponding to an effective nucleus radius of r{sub e} = 0.30 {+-} 0.02 km, assuming an R-band albedo of p{sub R} = 0.05. We also revisit observations reported for 259P while it was active in 2008 to quantify the dust mass loss and compare the object with other known main-belt comets.

  19. The nucleus 24 contour cochlear implant system: adult clinical trial results.

    Science.gov (United States)

    Parkinson, Aaron J; Arcaroli, Jennifer; Staller, Steven J; Arndt, Patti L; Cosgriff, Anne; Ebinger, Kiara

    2002-02-01

    The purpose of this article is to present psychophysical data for 40 Nucleus 24 Contour adult patients with 1 mo of device experience and speech perception results for a group of 56 adult patients with 3 mo experience using the Nucleus 24 Contour cochlear implant system. Postoperative hearing thresholds (i.e., under headphones) in the implanted ear were also assessed in a group of 85 patients who had measurable hearing preoperatively. This was of interest because preservation of residual hearing, postoperatively, is consistent with atraumatic insertion of the electrode array. In addition, data will be presented that reflected feedback from 40 surgeons who participated in the trial. Participants in this study were 18 yr of age or older, with bilateral severe to profound sensorineural hearing loss with no congenital component. Preoperatively, they scored hearing thresholds were compared with unaided thresholds in the implanted ear measured 1 mo after device activation. Surgeons were canvassed regarding surgical use and design of the device via a questionnaire after having completed at least one Nucleus 24 Contour surgery. Average T- and C-levels for the Nucleus 24 Contour patients were considerably lower than those using the Nucleus 24 (CI24M). A total of 85 patients had measurable hearing preoperatively at two or more audiometric frequencies in the ear implanted. Of these patients 41 (48%) had measurable hearing at one or more frequencies and 32 (38%) had measurable hearing at two or more frequencies postoperatively. In general, surgeons found the Nucleus 24 Contour easy to insert and were pleased with the design features of the device. The downsized receiver/stimulator (of the Nucleus 24 Contour) required less drilling than the Nucleus 24, reducing surgical time, as well as making the Contour better suited for implantation in those with small skull sizes (e.g., small children and infants). After 3 mo of device use, mean open-set speech perception in quiet and in

  20. Differential transcriptome expression in human nucleus accumbens as a function of loneliness.

    Science.gov (United States)

    Canli, T; Wen, R; Wang, X; Mikhailik, A; Yu, L; Fleischman, D; Wilson, R S; Bennett, D A

    2017-07-01

    Loneliness is associated with impaired mental and physical health. Studies of lonely individuals reported differential expression of inflammatory genes in peripheral leukocytes and diminished activation in brain reward regions such as nucleus accumbens, but could not address gene expression in the human brain. Here, we examined genome-wide RNA expression in post-mortem nucleus accumbens from donors (N=26) with known loneliness measures. Loneliness was associated with 1710 differentially expressed transcripts and genes from 1599 genes (DEGs; false discovery rate Ploneliness in this sample, although gene expression analyses controlled for AD diagnosis). These results identify novel targets for future mechanistic studies of gene networks in nucleus accumbens and gene regulatory mechanisms across a variety of diseases exacerbated by loneliness.

  1. The NIMA-related kinase NEK1 cycles through the nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Hilton, Laura K.; White, Mark C. [Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby (Canada); Quarmby, Lynne M., E-mail: quarmby@sfu.ca [Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby (Canada)

    2009-11-06

    Mutations in NEK1 in mice are causal for cystic kidneys, and model the ciliopathy polycystic kidney disease caused by abnormal ciliary structure or signaling. NEK1 has previously been shown to localize near centrosomes and to play a role in centrosomal stability and ciliogenesis. Recent data suggest that the etiology of kidney cysts involves aberrant signaling from the primary cilium to the nucleus. Here we demonstrate that NEK1 contains functional nuclear localization signals, is exported from the nucleus via a nuclear export signal-dependent pathway and that the protein cycles through the nucleus. Our data suggest that NEK1 is a candidate to transduce messages from the ciliary-basal body region to the regulation of nuclear gene expression.

  2. Neonatal handling, sweet food ingestion and ectonucleotidase activities in nucleus accumbens at different ages.

    Science.gov (United States)

    Silveira, P P; Cognato, G; Crema, L M; Pederiva, F Q; Bonan, C D; Sarkis, J J; Lucion, A B; Dalmaz, C

    2006-05-01

    Neonatal handled rats ingest more sweet food than non-handled ones, but it was documented only after puberty. Here, we studied the purinergic system in the nucleus accumbens, a possible target for the alteration in the preference for palatable food. We measured the ATP, ADP and AMP hydrolysis mediated by ectonucleotidases in synaptosomes of the nucleus accumbens in periadolescent and adult rats from different neonatal environments: non-handled and handled (10 min/day, first 10 days of life). Before adolescence, we found a decreased ingestion of sweet food in the neonatally handled group, with no effect on ATP, ADP or AMP hydrolysis. In adults, we found a greater ingestion of sweet food in the neonatally handled group, with no effect on ATPase or ADPase activities, but a decreased AMP hydrolysis. The nucleus accumbens is a site of intensive interaction between the adenosinergic and dopaminergic systems. Therefore, adenosine may modulate accumbens' dopamine neurotransmission differently in neonatally handled rats.

  3. Cometary science. On the nucleus structure and activity of comet 67P/Churyumov-Gerasimenko.

    Science.gov (United States)

    Sierks, Holger; Barbieri, Cesare; Lamy, Philippe L; Rodrigo, Rafael; Koschny, Detlef; Rickman, Hans; Keller, Horst Uwe; Agarwal, Jessica; A'Hearn, Michael F; Angrilli, Francesco; Auger, Anne-Therese; Barucci, M Antonella; Bertaux, Jean-Loup; Bertini, Ivano; Besse, Sebastien; Bodewits, Dennis; Capanna, Claire; Cremonese, Gabriele; Da Deppo, Vania; Davidsson, Björn; Debei, Stefano; De Cecco, Mariolino; Ferri, Francesca; Fornasier, Sonia; Fulle, Marco; Gaskell, Robert; Giacomini, Lorenza; Groussin, Olivier; Gutierrez-Marques, Pablo; Gutiérrez, Pedro J; Güttler, Carsten; Hoekzema, Nick; Hviid, Stubbe F; Ip, Wing-Huen; Jorda, Laurent; Knollenberg, Jörg; Kovacs, Gabor; Kramm, J Rainer; Kührt, Ekkehard; Küppers, Michael; La Forgia, Fiorangela; Lara, Luisa M; Lazzarin, Monica; Leyrat, Cédric; Lopez Moreno, Josè J; Magrin, Sara; Marchi, Simone; Marzari, Francesco; Massironi, Matteo; Michalik, Harald; Moissl, Richard; Mottola, Stefano; Naletto, Giampiero; Oklay, Nilda; Pajola, Maurizio; Pertile, Marco; Preusker, Frank; Sabau, Lola; Scholten, Frank; Snodgrass, Colin; Thomas, Nicolas; Tubiana, Cecilia; Vincent, Jean-Baptiste; Wenzel, Klaus-Peter; Zaccariotto, Mirco; Pätzold, Martin

    2015-01-23

    Images from the OSIRIS scientific imaging system onboard Rosetta show that the nucleus of 67P/Churyumov-Gerasimenko consists of two lobes connected by a short neck. The nucleus has a bulk density less than half that of water. Activity at a distance from the Sun of >3 astronomical units is predominantly from the neck, where jets have been seen consistently. The nucleus rotates about the principal axis of momentum. The surface morphology suggests that the removal of larger volumes of material, possibly via explosive release of subsurface pressure or via creation of overhangs by sublimation, may be a major mass loss process. The shape raises the question of whether the two lobes represent a contact binary formed 4.5 billion years ago, or a single body where a gap has evolved via mass loss. Copyright © 2015, American Association for the Advancement of Science.

  4. The NIMA-related kinase NEK1 cycles through the nucleus.

    Science.gov (United States)

    Hilton, Laura K; White, Mark C; Quarmby, Lynne M

    2009-11-06

    Mutations in NEK1 in mice are causal for cystic kidneys, and model the ciliopathy polycystic kidney disease caused by abnormal ciliary structure or signaling. NEK1 has previously been shown to localize near centrosomes and to play a role in centrosomal stability and ciliogenesis. Recent data suggest that the etiology of kidney cysts involves aberrant signaling from the primary cilium to the nucleus. Here we demonstrate that NEK1 contains functional nuclear localization signals, is exported from the nucleus via a nuclear export signal-dependent pathway and that the protein cycles through the nucleus. Our data suggest that NEK1 is a candidate to transduce messages from the ciliary-basal body region to the regulation of nuclear gene expression.

  5. Deep brain stimulation of the subthalamic nucleus: anatomical, neurophysiological, and outcome correlations with the effects of stimulation

    National Research Council Canada - National Science Library

    Lanotte, M M; Rizzone, M; Bergamasco, B; Faccani, G; Melcarne, A; Lopiano, L

    2002-01-01

    Bilateral chronic high frequency stimulation of the subthalamic nucleus (STN), through the stereotactical placement of stimulating electrodes, effectively improves the motor symptoms of severe Parkinson's disease...

  6. Synaptic interactions between perifornical lateral hypothalamic area, locus coeruleus nucleus and the oral pontine reticular nucleus are implicated in the stage succession during sleep-wakefulness cycle

    Directory of Open Access Journals (Sweden)

    Angel eNunez

    2013-11-01

    Full Text Available The perifornical area in the posterior lateral hypothalamus (PeFLH has been implicated in several physiological functions including the sleep-wakefulness regulation. The PeFLH area contains several cell types including those expressing orexins (Orx; also known as hypocretins, mainly located in the PeF nucleus. The aim of the present study was to elucidate the synaptic interactions between Orx neurons located in the PeFLH area and different brainstem neurons involved in the generation of wakefulness and sleep stages such as the locus coeruleus (LC nucleus (contributing to wakefulness and the oral pontine reticular nucleus (PnO nucleus (contributing to REM sleepAnatomical data demonstrated the existence of a neuronal network involving the PeFLH area, LC and the PnO nuclei that would control the sleep-wake cycle. Electrophysiological experiments indicated that PeFLH area had an excitatory effect on LC neurons. PeFLH stimulation increased the firing rate of LC neurons and induced an activation of the EEG. The excitatory effect evoked by PeFLH stimulation in LC neurons was blocked by the injection of the Orx-1 receptor antagonist SB-334867 into the LC. Similar electrical stimulation of the PeFLH area evoked an inhibition of PnO neurons by activation of GABAergic receptors because the effect was blocked by bicuculline application into the PnO. Our data also revealed that the LC and PnO nuclei exerted a feedback control on neuronal activity of PeFLH area. Electrical stimulation of LC facilitated firing activity of PeFLH neurons by activation of catecholaminergic receptors whereas PnO stimulation inhibited PeFLH neurons by activation of GABAergic receptors. In conclusion, Orx neurons of the PeFLH area seem to be an important organizer of the wakefulness and sleep stages in order to maintain a normal succession of stages during the sleep-wakefulness cycle.

  7. Neonatal handling reduces angiotensin II receptor density in the medial preoptic area and paraventricular nucleus but not in arcuate nucleus and locus coeruleus of female rats.

    Science.gov (United States)

    Gomes, Cármen Marilei; Donadio, Márcio Vinícius Fagundes; Franskoviaki, Inélia; Anselmo-Franci, Janete A; Franci, Celso Rodrigues; Lucion, Aldo Bolten; Sanvitto, Gilberto Luiz

    2006-01-05

    Neonatal handling alters the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonads axis (HPG) in adult animals, and angiotensin II (Ang II) modulates the functions in these axes. We tested whether neonatal handling could change the density of Ang II receptors in some central areas in female rats. Results showed decreased density of the Ang II receptors in the medial preoptic area (MPOA) and hypothalamic paraventricular nucleus (PVN) of the neonatal handled group.

  8. Determination of primary energy in nucleus-nucleus collisions and the high P(sub)T tail of alpha-particles

    Science.gov (United States)

    Freier, P. S.; Atwater, T. W.

    1985-01-01

    A determination of primary energy is required in order to study the energy dependence of meson multiplicity in A-A collisions in cosmic rays. Various procedures which estimate the energy of a primary nucleus from its interaction were investigated. An average of two methods were used, one using the pions and wounded protons and the other using spectator protons and alpha particles. The high P sub T tail observed for Z = 2 fragments requires a modification of the latter method.

  9. Photometric properties of the nucleus of Comet 103P/Hartley 2

    Science.gov (United States)

    Li, Jian-Yang; Besse, Sébastien; A'Hearn, Michael F.; Belton, Michael J. S.; Bodewits, Dennis; Farnham, Tony L.; Klaasen, Kenneth P.; Lisse, Carey M.; Meech, Karen J.; Sunshine, Jessica M.; Thomas, Peter C.

    2013-02-01

    We have studied the photometric properties of the nucleus of a hyperactive comet, 103P/Hartley 2, at visible wavelengths using the DIXI flyby images with both disk-integrated and disk-resolved analyses. The disk-integrated phase function of the nucleus has a linear slope of 0.046 ± 0.002 mag/deg and an absolute magnitude of 18.4 ± 0.1 at V-band. The nucleus displays an overall linear, featureless spectrum between 400 nm and 850 nm. The linear spectral slope is 7.6 ± 3.6% per 100 nm, corresponding to broadband solar-illuminated color indices B-V of 0.75 ± 0.05 and V-R of 0.43 ± 0.04. Disk-resolved photometric analysis with a Hapke model returns a best-fit single-scattering albedo of 0.036 ± 0.006, an asymmetry factor of the Henyey-Greenstein single-particle phase function of -0.46 ± 0.06, and a photometric roughness of 15 ± 10°. The model yields a geometric albedo of 0.045 ± 0.009 and a Bond albedo of 0.012 ± 0.002. The overall photometric variations of the nucleus are small, with an equivalent albedo variation of 15% FWHM, and a color variation of 12% FWHM. Some areas near the terminator visible in the inbound images show an albedo of more than twice the global average value, and a much bluer color than the average nucleus. The overall photometric properties and variations of the nucleus of Hartley 2 are similar to those of the nuclei of Comets Wild 2 and Tempel 1 as studied from previous spacecraft flyby missions at similar resolutions.

  10. Targeted delivery of peptide-conjugated biocompatible gold nanoparticles into cancer cell nucleus

    Science.gov (United States)

    Qian, Wei; Curry, Taeyjuana; Che, Yong; Kopelman, Raoul

    2013-02-01

    Nucleus remains a significant target for nanoparticles with diagnostic and therapeutic applications because both genetic information of the cell and transcription machinery reside there. Novel therapeutic strategies (for example, gene therapy), enabled by safe and efficient delivery of nanoparticles and drug molecules into the nucleus, are heralded by many as the ultimate treatment for severe and intractable diseases. However, most nanomaterials and macromolecules are incapable of reaching the cell nucleus on their own, because of biological barriers carefully honed by evolution including cellular membrane and nuclear envelope. In this paper, we have demonstrated an approach of fabrication of biocompatible gold nanoparticle (Au NP)-based vehicles which can entering into cancer cell nucleus by modifying Au NPs with both PEG 5000 and two different peptides (RGD and nuclear localization signal (NLS) peptide). The Au NPs used were fabricated via femtosecond laser ablation of Au bulk target in deionized water. The Au NPs produced by this method provide chemical free, virgin surface, which allows us to carry out "Sequential Conjugation" to modify their surface with PEG 5000, RGD, and NLS. "Sequential Conjugation" described in this presentation is very critical for the fabrication of Au NP-based vehicles capable of entering into cancer cell nucleus as it enables the engineering and tuning surface chemistries of Au NPs by independently adjusting amounts of PEG and peptides bound onto surface of Au NPs so as to maximize their nuclear targeting performance and biocompatibility regarding the cell line of interest. Both optical microscopy and transmission electron microscopy (TEM) are used to confirm the in vitro targeted nuclear delivery of peptide-conjugated biocompatible Au NPs by showing their presence in the cancer cell nucleus.

  11. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    Science.gov (United States)

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Segmentation and volumetric analysis of the caudate nucleus in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Jiji, Sudevan, E-mail: jijiaiswaryap@gmail.com [Department of Optoelectronics, University of Kerala, Kariavattom, Trivandrum 695581, Kerala (India); Smitha, Karavallil Achuthan, E-mail: mithamahesh@gmail.com [Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695012, Kerala (India); Gupta, Arun Kumar, E-mail: gupta209@gmail.com [Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India); Pillai, Vellara Pappukutty Mahadevan, E-mail: vpmpillai9@gmail.com [Department of Optoelectronics, University of Kerala, Kariavattom, Trivandrum 695581, Kerala (India); Jayasree, Ramapurath S., E-mail: jayashreemenon@gmail.com [Biophotonics and Imaging Lab, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695012, Kerala (India)

    2013-09-15

    Objectives: A quantitative volumetric analysis of caudate nucleus can provide valuable information in early diagnosis and prognosis of patients with Alzheimer's diseases (AD). Purpose of the study is to estimate the volume of segmented caudate nucleus from MR images and to correlate the variation in the segmented volume with respect to the total brain volume. We have also tried to evaluate the caudate nucleus atrophy with the age related atrophy of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) in a group of Alzheimer's disease patients. Methods: 3D fast low angle shot (3D FLASH) brain MR images of 15 AD patients, 15 normal volunteers and 15 patients who had normally diagnosed MR images were included in the study. Brain tissue and caudate nuclei were segmented using the statistical parametric mapping package and a semi-automatic tool, respectively and the volumes were estimated. Volume of segmented caudate nucleus is correlated with respect to the total brain volume. Further, the caudate nucleus atrophy is estimated with the age related atrophy of WM, GM and CSF in a group of AD patients. Results: Significant reduction in the caudate volume of AD patients was observed compared to that of the normal volunteers. Statistical analysis also showed significant variation in the volume of GM and CSF of AD patients. Among the patients who had normal appearing brain, 33% showed significant changes in the caudate volume. We hypothesize that these changes can be considered as an indication of early AD. Conclusion: The method of volumetric analysis of brain structures is simple and effective way of early diagnosis of neurological disorders like Alzheimer's disease. We have illustrated this with the observed changes in the volume of caudate nucleus in a group of patients. A detailed study with more subjects will be useful in correlating these results for early diagnosis of AD.