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Sample records for corteza prefrontal medial

  1. Estudio de la asimetría interhemisférica en la corteza prefrontal dorsolateral de sujetos humanos

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    Hernán J. Pimienta J.; Gabriel Arteaga

    2005-01-01

    Se presentan los resultados de un trabajo de investigación encaminado a establecer las diferencias entre los hemisferios cerebrales de la corteza prefrontal dorsolateral: áreas 46 laeral y 7 medial, de sujetos humanos.

  2. Estudio de la asimetría interhemisférica en la corteza prefrontal dorsolateral de sujetos humanos

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    Hernán J. Pimienta J.

    2005-03-01

    Full Text Available Se presentan los resultados de un trabajo de investigación encaminado a establecer las diferencias entre los hemisferios cerebrales de la corteza prefrontal dorsolateral: áreas 46 laeral y 7 medial, de sujetos humanos.

  3. Hierarchical error representation in medial prefrontal cortex.

    Science.gov (United States)

    Zarr, Noah; Brown, Joshua W

    2016-01-01

    The medial prefrontal cortex (mPFC) is reliably activated by both performance and prediction errors. Error signals have typically been treated as a scalar, and it is unknown to what extent multiple error signals may co-exist within mPFC. Previous studies have shown that lateral frontal cortex (LFC) is arranged in a hierarchy of abstraction, such that more abstract concepts and rules are represented in more anterior cortical regions. Given the close interaction between lateral and medial prefrontal cortex, we explored the hypothesis that mPFC would be organized along a similar rostro-caudal gradient of abstraction, such that more abstract prediction errors are represented further anterior and more concrete errors further posterior. We show that multiple prediction error signals can be found in mPFC, and furthermore, these are arranged in a rostro-caudal gradient of abstraction which parallels that found in LFC. We used a task that requires a three-level hierarchy of rules to be followed, in which the rules changed without warning at each level of the hierarchy. Task feedback indicated which level of the rule hierarchy changed and led to corresponding prediction error signals in mPFC. Moreover, each identified region of mPFC was preferentially functionally connected to correspondingly anterior regions of LFC. These results suggest the presence of a parallel structure between lateral and medial prefrontal cortex, with the medial regions monitoring and evaluating performance based on rules maintained in the corresponding lateral regions.

  4. Optogenetic dissection of medial prefrontal cortex circuitry

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    Danai eRiga

    2014-12-01

    Full Text Available The medial prefrontal cortex (mPFC is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g. thalamus, striatum, amygdala and hippocampus, the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

  5. Optogenetic dissection of medial prefrontal cortex circuitry.

    Science.gov (United States)

    Riga, Danai; Matos, Mariana R; Glas, Annet; Smit, August B; Spijker, Sabine; Van den Oever, Michel C

    2014-01-01

    The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

  6. Medial prefrontal D1 dopamine neurons control food intake.

    Science.gov (United States)

    Land, Benjamin B; Narayanan, Nandakumar S; Liu, Rong-Jian; Gianessi, Carol A; Brayton, Catherine E; Grimaldi, David M; Sarhan, Maysa; Guarnieri, Douglas J; Deisseroth, Karl; Aghajanian, George K; DiLeone, Ralph J

    2014-02-01

    Although the prefrontal cortex influences motivated behavior, its role in food intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor-expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and optogenetic photostimulation of D1 neurons increases feeding. Conversely, inhibition of D1 neurons decreases intake. Stimulation-based mapping of prefrontal D1 neuron projections implicates the medial basolateral amygdala (mBLA) as a downstream target of these afferents. mBLA neurons activated by prefrontal D1 stimulation are CaMKII positive and closely juxtaposed to prefrontal D1 axon terminals. Finally, photostimulating these axons in the mBLA is sufficient to increase feeding, recapitulating the effects of mPFC D1 stimulation. These data describe a new circuit for top-down control of food intake.

  7. Exposición al cadmio y efectos neurotóxicos en corteza prefrontal

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    A. Romero

    2005-01-01

    Full Text Available Cadmium neurotoxicity is known in different brain areas, but not as much in the prefrontal cortex (CPF. The objective of the present work is to study the chan ges induced by cadmium on the circadian patterns of the biogenic amines and the metabolism of the dopamine and the serotonin in this brain area in. Cadmium has been administered for 3 0 days like cadmium chloride (CdCl2, at a dose 25 ppm dissolved in the drinking water. Biogenic amines and their main metabolites were measured within in CPF through HPLC-EQ. In cad mium treated rats, norepinefrine circadian pattern was modified, mean levels of dopamin e (DA were increased while dopamine metabolism (expressed as the DOPAC/DA rate decreased . The exposure to the cadmium induced also important changes in the daily pattern of the 5 -hydroxiindolacetic acid (main metabolite of the serotonin and the disappearance of the circ adian pattern of this indolamine

  8. Anatomical segmentation of the human medial prefrontal cortex

    NARCIS (Netherlands)

    Corcoles-Parada, M.; Muller, N.C.J.; Ubero, M.; Serrano-Del-Pueblo, V.M.; Mansilla, F.; Marcos-Rabal, P.; Artacho-Perula, E.; Dresler, M.; Insausti, R.; Fernandez, G.; Munoz-Lopez, M.

    2017-01-01

    The medial prefrontal areas 32, 24, 14, and 25 (mPFC) form part of the limbic memory system, but little is known about their functional specialization in humans. To add anatomical precision to structural and functional magnetic resonance imaging (MRI) data, we aimed to identify these mPFC subareas i

  9. Dopaminergic Activity in the Medial Prefrontal Cortex Modulates Fear Conditioning

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    Parvin Babaei

    2011-07-01

    Full Text Available "nThe purpose of the present study was to determine the role of medial prefrontal cortex (mPFC dopaminergic system in fear conditioning response considering individual differences. Animals were initially counterbalanced and classified based on open field test, and then were given a single infusion of the dopamine agonist, amphetamine (AMPH and antagonist, clozapine (CLZ into the medial prefrontal cortex. Rats received tone-shock pairing in a classical fear conditioning test and then exposed to the tone alone. Freezing responses were measured as conditioned fear index. The results showed that both AMPH and CLZ infusion in mPFC reduced the expression of conditioned fear. This finding indicates that elevation or reduction in the dopaminergic activity is associated with the decrease of fear responses, despite preexisting individual-typological differences.

  10. Neurochemical metabolites in the medial prefrontal cortex in bipolar disorder A proton magnetic resonance spectroscopy study

    Institute of Scientific and Technical Information of China (English)

    Osman (O)zdel; Demet Kalayci; Gülfizar S(o)zeri-Varma; Yilmaz Kiro(g)lu; Selim Tümkaya; Tu(g)(c)e Toker-U(g)urlu

    2012-01-01

    The aim of this study was to investigate proton magnetic resonance spectroscopy metabolite values in the medial prefrontal cortex of individuals with euthymic bipolar disorder. The subjects consisted of 15 patients with euthymic bipolar disorder type I and 15 healthy controls. We performed proton magnetic resonance spectroscopy of the bilateral medial prefrontal cortex and measured levels of N-acetyl aspartate, choline and creatine. Levels of these three metabolites in the medial prefrontal cortex were found to be lower in patients with bipolar disorder compared with healthy controls. A positive correlation was found between illness duration and choline levels in the right medial prefrontal cortex. Our study suggests that during the euthymic period, there are abnormalities in cellular energy and membrane phospholipid metabolism in the medial prefrontal cortex, and that this may impair neuronal activity and integrity.

  11. Watching cartoons activates the medial prefrontal cortex in children

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The medial prefrontal cortex (MPFC) of human adults is involved in attributing mental states to real human agents but not to virtual artificial characters. This study examined whether such differential MPFC activity can be observed in children who are more fascinated by cartoons than adults. We measured brain activity using functional magnetic resonance imaging (fMRI) while 10-year-old children watched movie and cartoon clips, simulating real and virtual visual worlds, respectively. We showed neuroimaging evidence that, in contrast to adults, the MPFC of children was activated when perceiving both human agents and artificial characters in coherent visual events. Our findings suggest that, around the age of 10 years, the MPFC activity in children is different from that in adults in that it can be spontaneously activated by non-human agents in a virtual visual world.

  12. A general role for medial prefrontal cortex in event prediction

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    William H Alexander

    2014-07-01

    Full Text Available A recent computational neural model of medial prefrontal cortex (mPFC, namely the PRO model (Alexander & Brown, 2011, suggests that mPFC learns to predict the outcomes of actions. The model accounted for a wide range of data on the mPFC. Nevertheless, numerous recent findings suggest that mPFC may signal predictions and prediction errors even when the predicted outcomes are not contingent on prior actions. Here we show that the existing PRO model can learn to predict outcomes in a general sense, and not only when the outcomes are contingent on actions. A series of simulations show how this generalized PRO model can account for an even broader range of findings in the mPFC, including human ERP, fMRI, and macaque single-unit data. The results suggest that the mPFC learns to predict salient events in general and provides a theoretical framework that links mPFC function to model-based reinforcement learning, Bayesian learning, and theories of cognitive control.

  13. Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex.

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    Glasper, Erica R; LaMarca, Elizabeth A; Bocarsly, Miriam E; Fasolino, Maria; Opendak, Maya; Gould, Elizabeth

    2015-11-01

    The medial prefrontal cortex is important for cognitive flexibility, a capability that is affected by environmental conditions and specific experiences. Aversive experience, such as chronic restraint stress, is known to impair performance on a task of cognitive flexibility, specifically attentional set-shifting, in rats. Concomitant with this performance decrement, chronic stress reduces the number of dendritic spines on pyramidal neurons in the medial prefrontal cortex. No previous studies have examined whether a rewarding experience, namely mating, affects cognitive flexibility and dendritic spines in the medial prefrontal cortex of male rats. To test this possibility, we exposed adult male rats to sexual receptive females once daily for one week, assessed attentional set-shifting performance, and then analyzed their brains for changes in dendritic spines. We found that sexual experience improved performance on extradimensional set-shifting, which is known to require the medial prefrontal cortex. Additionally, we observed increased dendritic spine density on apical and basal dendrites of pyramidal neurons in the medial prefrontal cortex, but not the orbitofrontal cortex, after sexual experience. We also found that sexual experience enhanced dendritic spine density on granule neurons of the dentate gyrus. The ventral hippocampus sends a direct projection to the medial prefrontal cortex, raising the possibility that experience-dependent changes in the hippocampus are necessary for alterations in medial prefrontal cortex structure and function. As a first attempt at investigating this, we inactivated the ventral hippocampus with the GABA agonist muscimol, after each daily bout of sexual experience to observe whether the beneficial effects on cognitive flexibility were abolished. Contrary to our hypothesis, blocking hippocampal activity after sexual experience had no impact on enhanced cognitive flexibility. Taken together, these findings indicate that sexual

  14. Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults

    NARCIS (Netherlands)

    Meer, van Floor; Laan, van der Laura N.; Viergever, Max A.; Adan, Roger A.H.; Smeets, Paul A.M.

    2017-01-01

    Childhood obesity is a rising problem worldwide mainly caused by overconsumption, which is driven by food choices. In adults, food choices are based on a value signal encoded in the medial prefrontal cortex (mPFC). This signal is modulated by the dorsolateral prefrontal cortex (dlPFC), which is

  15. Segregation of the human medial prefrontal cortex in social cognition

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    Danilo eBzdok

    2013-05-01

    Full Text Available While the human medial prefrontal cortex (mPFC is widely believed to be a key node of neural networks relevant for socio-emotional processing, its functional subspecialization is still poorly understood. We thus revisited the often assumed differentiation of the mPFC in social cognition along its ventral-dorsal axis. Our neuroinformatic analysis was based on a neuroimaging meta-analysis of perspective-taking that yielded two separate clusters in the ventral and dorsal mPFC, respectively. We determined each seed region’s brain-wide interaction pattern by two complementary measures of functional connectivity: co-activation across a wide range of neuroimaging studies archived in the BrainMap database and correlated signal fluctuations during unconstrained (resting cognition. Furthermore, we characterized the functions associated with these two regions using the BrainMap database. Across methods, the ventral mPFC was more strongly connected with the nucleus accumbens, hippocampus, posterior cingulate cortex, and retrosplenial cortex, while the dorsal mPFC was more strongly connected with the inferior frontal gyrus, temporo-parietal junction, and middle temporal gyrus. Further, the ventral mPFC was selectively associated with action execution, olfaction, and reward related tasks, while the dorsal mPFC was selectively associated with perspective-taking and episodic memory retrieval. The ventral mPFC is therefore predominantly involved in sensory-driven, approach/avoidance-modulating, and evaluation-related processing, whereas the dorsal mPFC is predominantly involved in internally driven, memory-informed, and metacognition-related processing in social cognition.

  16. Medial Prefrontal Cortex and HPA Axis Roles in Generation of PTSD-Like Symptoms in SPS Model

    Science.gov (United States)

    2011-09-01

    AD_________________ Award Number: W81XWH-08-1-0661 TITLE: Medial Prefrontal Cortex and HPA Axis...August 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Medial Prefrontal Cortex and HPA Axis Roles In Generation of PTSD-Like Symptoms In SPS Model...emotional regulation (specific aim #3). 15. SUBJECT TERMS PTSD, SPS, anxiety, fear, conditioning, prefrontal cortex , hippocampus, amygdala 16

  17. Multimodal intervention in older adults improves resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe.

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    Li, Rui; Zhu, Xinyi; Yin, Shufei; Niu, Yanan; Zheng, Zhiwei; Huang, Xin; Wang, Baoxi; Li, Juan

    2014-01-01

    The prefrontal cortex and medial temporal lobe are particularly vulnerable to the effects of aging. The disconnection between them is suggested to be an important cause of cognitive decline in normal aging. Here, using multimodal intervention training, we investigated the functional plasticity in resting-state connectivity of these two regions in older adults. The multimodal intervention, comprised of cognitive training, Tai Chi exercise, and group counseling, was conducted to explore the regional connectivity changes in the default-mode network, as well as changes in prefrontal-based voxel-wise connectivity in the whole brain. Results showed that the intervention selectively affected resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe. Moreover, the strength of resting-state functional connectivity between these regions correlated with individual cognitive performance. Our results suggest that multimodal intervention could postpone the effects of aging and improve the function of the regions that are most heavily influenced by aging, as well as play an important role in preserving the brain and cognition during old age.

  18. Multimodal intervention in older adults improves resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe

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    Rui eLi

    2014-03-01

    Full Text Available The prefrontal cortex and medial temporal lobe are particularly vulnerable to the effects of aging. The disconnection between them is suggested to be an important cause of cognitive decline in normal aging. Here, using multimodal intervention training, we investigated the functional plasticity in resting-state connectivity of these two regions in older adults. The multimodal intervention, comprised of cognitive training, Tai Chi exercise, and group counseling, was conducted to explore the regional connectivity changes in the default-mode network, as well as changes in prefrontal-based voxel-wise connectivity in the whole brain. Results showed that the intervention selectively affected resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe. Moreover, the strength of resting-state functional connectivity between these regions correlated with individual cognitive performance. Our results suggest that multimodal intervention could postpone the effects of aging and improve the function of the regions that are most heavily influenced by aging, as well as play an important role in preserving the brain and cognition during old age.Clinical Trial Registration: This trial was registered in the Chinese Clinical Trial Registry (ChiCTR (http://www.chictr.org: ChiCTR-PNRC-13003813.

  19. Avances en corteza auditiva

    OpenAIRE

    Jara O,Natalia; Délano R,Paul H

    2014-01-01

    El sistema auditivo nos permite detectar e interpretar las señales acústicas del medio ambiente y así modificar nuestro comportamiento. En humanos la corteza auditiva se ubica en el giro temporal superior del lóbulo temporal. Esta corteza presenta una organización estructural y funcional característica, que se ha identificado en muchas especies de mamíferos. Las áreas de organización de la corteza auditiva son: (i) una región central denominada corteza auditiva primaria o core, que correspond...

  20. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

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    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  1. Disruption of the Perineuronal Net in the Hippocampus or Medial Prefrontal Cortex Impairs Fear Conditioning

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    Hylin, Michael J.; Orsi, Sara A.; Moore, Anthony N.; Dash, Pramod K.

    2013-01-01

    The perineuronal net (PNN) surrounds neurons in the central nervous system and is thought to regulate developmental plasticity. A few studies have shown an involvement of the PNN in hippocampal plasticity and memory storage in adult animals. In addition to the hippocampus, plasticity in the medial prefrontal cortex (mPFC) has been demonstrated to…

  2. Medial Prefrontal Cortex Is Selectively Involved in Response Selection Using Visual Context in the Background

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    Lee, Inah; Shin, Ji Yun

    2012-01-01

    The exact roles of the medial prefrontal cortex (mPFC) in conditional choice behavior are unknown and a visual contextual response selection task was used for examining the issue. Inactivation of the mPFC severely disrupted performance in the task. mPFC inactivations, however, did not disrupt the capability of perceptual discrimination for visual…

  3. Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

    OpenAIRE

    María Carolina Gonzalez; Cecilia Paula Kramar; Micol eTomaiuolo; Cynthia eKatche; Noelia eWeisstaub; Martín eCammarota; Jorge Horacio Medina

    2014-01-01

    Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC imme...

  4. Cocaine-induced Modification of Synaptic Plasticity in Rat Medial Prefrontal Cortex

    OpenAIRE

    Lu, Hui

    2009-01-01

    Medial prefrontal cortex (mPFC) is involved in relapse after withdrawal for cocaine exposure, but changes in synaptic function and plasticity in the mPFC during the period of withdrawal remain largely unknown. After the termination of repeated cocaine treatments in rats, I observed a gradual enhancement in the susceptibility of excitatory synapses on layer V mPFC pyramidal neurons to activity-induced long-term potentiation (LTP). This enhanced synaptic plasticity could be attributed to a grad...

  5. Human Choice Strategy Varies with Anatomical Projections from Ventromedial Prefrontal Cortex to Medial Striatum.

    Science.gov (United States)

    Piray, Payam; Toni, Ivan; Cools, Roshan

    2016-03-09

    Two distinct systems, goal-directed and habitual, support decision making. It has recently been hypothesized that this distinction may arise from two computational mechanisms, model-based and model-free reinforcement learning, neuronally implemented in frontostriatal circuits involved in learning and behavioral control. Here, we test whether the relative strength of anatomical connectivity within frontostriatal circuits accounts for variation in human individuals' reliance on model-based and model-free control. This hypothesis was tested by combining diffusion tensor imaging with a multistep decision task known to distinguish model-based and model-free control in humans. We found large interindividual differences in the degree of model-based control, and those differences are predicted by the structural integrity of white-matter tracts from the ventromedial prefrontal cortex to the medial striatum. Furthermore, an analysis based on masking out of bottom-up tracts suggests that this effect is driven by top-down influences from ventromedial prefrontal cortex to medial striatum. Our findings indicate that individuals with stronger afferences from the ventromedial prefrontal cortex to the medial striatum are more likely to rely on a model-based strategy to control their instrumental actions. These findings suggest a mechanism for instrumental action control through which medial striatum determines, at least partly, the relative contribution of model-based and model-free systems during decision-making according to top-down model-based information from the ventromedial prefrontal cortex. These findings have important implications for understanding the neural circuitry that might be susceptible to pathological computational processes in impulsive/compulsive psychiatric disorders.

  6. An Increase in Tobacco Craving Is Associated with Enhanced Medial Prefrontal Cortex Network Coupling

    OpenAIRE

    Janes, Amy C.; Farmer, Stacey; Frederick, Blaise deB.; Nickerson, Lisa D.; Lukas, Scott E.

    2014-01-01

    Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI) in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefront...

  7. Effects of Methamphetamine on Single Unit Activity in Rat Medial Prefrontal Cortex In Vivo

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    Jinhwa Jang

    2007-01-01

    Full Text Available To investigate how neuronal activity in the prefrontal cortex changes in an animal model of schizophrenia, we recorded single unit activity in the medial prefrontal cortex of urethane-anesthetized and awake rats following methamphetamine (MA administration. Systemic MA injection (4 mg/kg, IP induced inconsistent changes, that is, both enhancement and reduction, in unit discharge rate, with a subset of neurons transiently (<30 min elevating their activities. The direction of firing rate change was poorly predicted by the mean firing rate or the degree of burst firing during the baseline period. Also, simultaneously recorded units showed opposite directions of firing rate change, indicating that recording location is a poor predictor of the direction of firing rate change. These results raise the possibility that systemic MA injection induces random bidirectional changes in prefrontal cortical unit activity, which may underlie some of MA-induced psychotic symptoms.

  8. Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats.

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    Sirohi, Sunil; Walker, Brendan M

    2015-11-01

    Opioid receptors can display spontaneous agonist-independent G-protein signaling (basal signaling/constitutive activity). While constitutive κ-opioid receptor (KOR) activity has been documented in vitro, it remains unknown if KORs are constitutively active in native systems. Using [(35) S] guanosine 5'-O-[gamma-thio] triphosphate coupling assay that measures receptor functional state, we identified the presence of medial prefrontal cortex KOR constitutive activity in young rats that declined with age. Furthermore, basal signaling showed an age-related decline and was insensitive to neutral opioid antagonist challenge. Collectively, the present data are first to demonstrate age-dependent alterations in the medial prefrontal cortex KOR constitutive activity in rats and changes in the constitutive activity of KORs can differentially impact KOR ligand efficacy. These data provide novel insights into the functional properties of the KOR system and warrant further consideration of KOR constitutive activity in normal and pathophysiological behavior. Opioid receptors exhibit agonist-independent constitutive activity; however, kappa-opioid receptor (KOR) constitutive activity has not been demonstrated in native systems. Our results confirm KOR constitutive activity in the medial prefrontal cortex (mPFC) that declines with age. With the ability to presynaptically inhibit multiple neurotransmitter systems in the mPFC, maturational or patho-logical alterations in constitutive activity could disrupt corticofugal glutamatergic pyramidal projection neurons mediating executive function. Regulation of KOR constitutive activity could serve as a therapeutic target to treat compromised executive function.

  9. Medial prefrontal depressor response: involvement of the rostral and caudal ventrolateral medulla in the rat.

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    Owens, N C; Verberne, A J

    2000-01-14

    The importance of neurones of the caudal and rostral ventrolateral medulla (CVLM and RVLM, respectively) in mediation of the medial prefrontal cortex depressor response was studied in halothane-anaesthetised rats. Blockade of GABA(A) receptors in the RVLM produced by microinjection of bicuculline (50 nl, 2 mM, n = 6) resulted in reversal of the depressor (-9.5 +/- 1.2 mm Hg) and lumbar sympathetic (-6.5 +/- 5.7 units) responses to pressor (+7.8 +/- 3.5 mm Hg) and sympathoexcitatory (+19.3 +/- 12.5 units) responses and simultaneous blockade of baroreceptor reflex-mediated sympathoinhibition. Baroreflex blockade was reflected by a significant reduction in the gain (slope of the blood pressure vs. lumbar sympathetic nerve discharge regression line) of the reflex. Microinjection of the excitatory amino acid antagonist kynurenic acid (100 nl, 50 mM, n = 6) into the CVLM blocked the baroreflex and significantly reduced the depressor (-9.6 +/- 0.4 to -6.9 +/- 0.6 mm Hg) and lumbar sympathetic (-4.0 +/- 2.1 to 2.9 +/- 1.9 units) responses to medial prefrontal cortex stimulation. These results support the hypothesis that the medial prefrontal cortex depressor response is mediated by a pathway which converges at the level of the RVLM and which is only partly dependent on an excitatory input to caudal ventrolateral medullary neurones.

  10. Group I metabotropic glutamate receptors in the medial prefrontal cortex: role in mesocorticolimbic glutamate release in cocaine sensitization.

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    Timmer, Kristin M; Steketee, Jeffery D

    2013-12-01

    Cocaine sensitization is associated with increased excitability of pyramidal projection neurons in the medial prefrontal cortex. Such hyperexcitability is presumed to increase glutamatergic input to the nucleus accumbens and ventral tegmental area. This study examined the effects of medial prefrontal cortex Group I metabotropic glutamate receptor activation on glutamate levels in the medial prefrontal cortex, nucleus accumbens, and ventral tegmental area in sensitized and control animals. Male Sprague-Dawley rats received four daily injections of cocaine (15 mg/kg, i.p.) or saline (1 mL/kg i.p.). One, 7, or 21 days from the fourth injection, dual-probe microdialysis experiments were performed wherein Group I metabotropic glutamate receptor agonist DHPG was infused into the medial prefrontal cortex and glutamate levels in this region as well as the nucleus accumbens or ventral tegmental area were examined. Intra-mPFC DHPG infusion increased glutamate levels in the medial prefrontal cortex at 1 and 7 days withdrawal, and in the nucleus accumbens at 21 days withdrawal in sensitized rats. These results suggest Group I metabotropic glutamate receptor activation may contribute to the increased excitability of medial prefrontal cortex pyramidal neurons in sensitized animals.

  11. Impaired executive function following ischemic stroke in the rat medial prefrontal cortex.

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    Cordova, Chris A; Jackson, Danielle; Langdon, Kristopher D; Hewlett, Krista A; Corbett, Dale

    2014-01-01

    Small (lacunar) infarcts frequently arise in frontal and midline thalamic regions in the absence of major stroke. Damage to these areas often leads to impairment of executive function likely as a result of interrupting connections of the prefrontal cortex. Thus, patients experience frontal-like symptoms such as impaired ability to shift ongoing behavior and attention. In contrast, executive dysfunction has not been demonstrated in rodent models of stroke, thereby limiting the development of potential therapies for human executive dysfunction. Male Sprague-Dawley rats (n=40) underwent either sham surgery or bilateral endothelin-1 injections in the mediodorsal nucleus of the thalamus or in the medial prefrontal cortex. Executive function was assessed using a rodent attention set shifting test that requires animals to shift attention to stimuli in different stimulus dimensions. Medial prefrontal cortex ischemia impaired attention shift performance between different stimulus dimensions while sparing stimulus discrimination and attention shifts within a stimulus dimension, indicating a selective attention set-shift deficit. Rats with mediodorsal thalamic lacunar damage did not exhibit a cognitive impairment relative to sham controls. The selective attention set shift impairment observed in this study is consistent with clinical data demonstrating selective executive disorders following stroke within specific sub-regions of frontal cortex. These data contribute to the development and validation of a preclinical animal model of executive dysfunction, that can be employed to identify potential therapies for ameliorating cognitive deficits following stroke.

  12. Differentiating functions of the lateral and medial prefrontal cortex in motor response inhibition.

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    H Rodrigo, Achala; Domenico, Stefano I Di; Ayaz, Hasan; Gulrajani, Sean; Lam, Jaeger; Ruocco, Anthony C

    2014-01-15

    The right inferior frontal gyrus is generally considered a critical region for motor response inhibition. Recent studies, however, suggest that the role of this cortical area in response inhibition may be overstated and that the contributions of other aspects of the prefrontal cortex are often overlooked. The current study used optical imaging to identify regions of the prefrontal cortex beyond the right inferior frontal gyrus which may serve to support motor response inhibition. Forty-three right-handed healthy adults completed a manual Go/No-Go task while evoked oxygenation of the prefrontal cortex was measured using 16-channel functional near-infrared spectroscopy. During motor response inhibition, the right inferior frontal gyrus, and to a lesser extent the homologous contralateral region, showed increased activation relative to a baseline task. Conversely, the medial prefrontal cortex was significantly deactivated, and the extent of reduced activity in this region was associated with fewer errors on the response inhibition task. These findings suggest a more substantial role of the left inferior frontal gyrus in response inhibition and possibly a distinct function of the middle frontal gyrus subserving error detection on manual motor control tasks.

  13. Cardiovascular responses of the anterior claustrum; its mechanism; contribution of medial prefrontal cortex.

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    Hatam, Masoumeh; Sheybanifar, Mehrnoosh; Nasimi, Ali

    2013-12-01

    The anterior claustrum (CLa) has bilateral connections with the areas involved in cardiovascular regulation, though its role in cardiovascular control is not yet understood. This study was performed to find the cardiovascular responsive region of the CLa by stimulating all parts of the CLa with l-glutamate, and to find the possible mechanisms mediating its responses in urethane-anesthetized rats. We also investigated the possible involvement of the medial prefrontal cortex in the cardiovascular responses of the CLa. The effect of microinjection of l-glutamate (50-100 nl, 0.25 M) was tested throughout the Cla and only in one area at 2.7 mm rostral to bregma, 1.8-2.0 midline and 4.5-5.6mm vertical, significant decreases in arterial pressure were elicited (-21.71±2.1 mmHg, P<0.001, t-test) with no significant change in heart rate. Administration (i.v.) of the muscarinic receptor blocker, atropine, had no effect on the change in mean arterial pressure in response to glutamate stimulation, suggesting that the parasympathetic system was not involved in this response. However, administration (i.v.) of the nicotinic receptor blocker, hexamethonium dichloride abolished the depressor response to glutamate, suggesting that CLa stimulation decreases sympathetic outflow to the cardiovascular system. In addition, microinjection of the reversible synaptic blocker, cobalt chloride, into the medial prefrontal cortex greatly attenuated the depressor response elicited by microinjection of glut into the CLa. Thus for the first time, we found the cardiovascular responsive region of the anterior claustrum. Also we showed that its response is mediated through the medial prefrontal cortex. © 2013.

  14. Divergent responses of inflammatory mediators within the amygdala and medial prefrontal cortex to acute psychological stress.

    Science.gov (United States)

    Vecchiarelli, Haley A; Gandhi, Chaitanya P; Gray, J Megan; Morena, Maria; Hassan, Kowther I; Hill, Matthew N

    2016-01-01

    There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. The aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of a wide range of inflammatory mediators across a broad temporal range, in key corticolimbic brain regions involved in the regulation of the stress response (amygdala, hippocampus, hypothalamus, medial prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30min or 120min of acute restraint stress and protein levels were examined 0h through 24h post-termination of 120min of acute restraint stress using both multiplex and ELISA methods. Our data demonstrate, for the first time, that exposure to acute psychological stress results in an increase in the protein level of several inflammatory mediators in the amygdala while concomitantly producing a decrease in the protein level of multiple inflammatory mediators within the medial prefrontal cortex. This pattern of changes seemed largely restricted to the amygdala and medial prefrontal cortex, with stress producing few changes in the mRNA or protein levels of inflammatory mediators within the hippocampus or hypothalamus. Consistent with previous research, stress resulted in a general elevation in multiple inflammatory mediators within the circulation. These data indicate that neuroinflammatory responses to stress do not appear to be generalized across brain structures and exhibit a high degree of spatiotemporal specificity. Given the impact of inflammatory signaling on neural excitability and emotional behavior, these data may provide a platform with which to explore the importance of inflammatory signaling within the prefrontocortical-amygdala circuit in the regulation of the neurobehavioral responses to stress.

  15. Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.

    Science.gov (United States)

    Gonzalez, Maria Carolina; Villar, Maria Eugenia; Igaz, Lionel M; Viola, Haydée; Medina, Jorge H

    2015-12-01

    The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions.

  16. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

    Science.gov (United States)

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects.

  17. Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy.

    Science.gov (United States)

    Rasgon, Natalie L; Kenna, Heather A; Wroolie, Tonita E; Williams, Katherine E; DeMuth, Bevin N; Silverman, Daniel H S

    2014-07-30

    Insulin resistance (IR) is a putative risk factor for cognitive decline and dementia, and has been shown to impede neuronal glucose metabolism in animal models. This post hoc study focused on metabolic changes in the medial prefrontal region, a brain region exhibiting decline years before documented cognitive changes, relative to high or low IR status in a cohort of postmenopausal women at risk for dementia who were randomized to continue or discontinue existing stable hormone therapy (HT) for 2 years. Subjects were dichotomized into high and low IR groups based on the homeostatic model assessment of insulin resistance, which was within clinically normal limits for the group as a whole at both baseline and 2-year follow-up. Results showed that high and low IR groups showed significant differences in metabolic decline of the medial prefrontal gyrus, regardless of HT randomization group. However, HT randomization was predictive of metabolic decline only in women with low HOMA (homeostatic assessment of insulin resistance). Performance in working memory was consistent with observed metabolic changes. These results suggest IR may be an independent moderator of regional metabolic changes, while protective metabolic effects of HT are most apparent in those at low-end range of IR. If replicated in future studies, these findings will help to better understand the interaction between putative risk and protective factors, and further delineate cohort postmenopausal women who may benefit from HT.

  18. Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study

    Institute of Scientific and Technical Information of China (English)

    Feng-Mei Fan; Shu-Ping Tan; Fu-De Yang; Yun-Long Tan; Yan-Li Zhao; Nan Chen; Bin-Bin Li

    2013-01-01

    People with schizophrenia exhibit impaired social cognitive functions,particularly emotion regulation.Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia,suggesting its important role in emotion processing in patients.We used the resting-state functional connectivity approach,setting a functionally relevant region,the vMPFC,as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients.We found hypo-connectivity between the vMPFC and the medial frontal cortex,right middle temporal lobe (MTL),right hippocampus,parahippocampal cortex (PHC) and amygdala.Further,there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas.Among these connectivity alterations,reduced vMPFCDLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale,while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients.These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia.The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.

  19. Attention, emotion, and deactivation of default activity in inferior medial prefrontal cortex

    DEFF Research Database (Denmark)

    Geday, Jacob; Gjedde, Albert

    2008-01-01

    Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with posi......Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC...... with positron emission tomography (PET) of labeled water (H(15)2O) uptake in brain of 14 healthy subjects. The subjects performed either a less demanding or a more demanding task of attention while they watched neutral and emotive images of people in realistic indoor or outdoor situations. In the less demanding...... task, subjects used the index finger to press any key when a new image appeared. In the more demanding task, subjects chose the index or middle finger to press separate keys for outdoor and indoor scenes. Compared to the less demanding task, in a global search of all gray matter, the more demanding...

  20. The role of the medial prefrontal cortex in the conditioning and extinction of fear

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

    Full Text Available Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD. As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL and infralimbic (IL subdivisions of the medial prefrontal cortex (mPFC regulate the expression and suppression of fear in rodents, respectively. Here we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

  1. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    OpenAIRE

    Radley, Jason J.; Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation ...

  2. Neural correlates of depth of strategic reasoning in medial prefrontal cortex.

    Science.gov (United States)

    Coricelli, Giorgio; Nagel, Rosemarie

    2009-06-09

    We used functional MRI (fMRI) to investigate human mental processes in a competitive interactive setting--the "beauty contest" game. This game is well-suited for investigating whether and how a player's mental processing incorporates the thinking process of others in strategic reasoning. We apply a cognitive hierarchy model to classify subject's choices in the experimental game according to the degree of strategic reasoning so that we can identify the neural substrates of different levels of strategizing. According to this model, high-level reasoners expect the others to behave strategically, whereas low-level reasoners choose based on the expectation that others will choose randomly. The data show that high-level reasoning and a measure of strategic IQ (related to winning in the game) correlate with the neural activity in the medial prefrontal cortex, demonstrating its crucial role in successful mentalizing. This supports a cognitive hierarchy model of human brain and behavior.

  3. Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

    Directory of Open Access Journals (Sweden)

    María Carolina Gonzalez

    2014-11-01

    Full Text Available Medial prefrontal cortex (mPFC is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-tem aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 hour later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus.

  4. Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

    Science.gov (United States)

    Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.

    2014-01-01

    Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318

  5. Distinct Contributions of the Basolateral Amygdala and the Medial Prefrontal Cortex to Learning and Relearning Extinction of Context Conditioned Fear

    Science.gov (United States)

    Laurent, Vincent; Westbrook, R. Frederick

    2008-01-01

    We studied the roles of the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in learning and relearning to inhibit context conditioned fear (freezing) in extinction. In Experiment 1, pre-extinction BLA infusion of the NMDA receptor (NMDAr) antagonist, ifenprodil, impaired the development and retention of inhibition but…

  6. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity.

    Science.gov (United States)

    Berkers, Ruud M W J; Klumpers, Floris; Fernández, Guillén

    2016-10-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that are characterized by 'overgeneralized' emotional memories. Here, we investigate the neural underpinnings of individual differences in emotional associative memory. A large group of healthy male participants were scanned while encoding associations of face-photographs and written occupational identities that were of either neutral ('driver') or negative ('murderer') valence. Subsequently, memory was tested by prompting participants to retrieve the occupational identities corresponding to each face. Whereas in both valence categories a similar amount of faces was labeled correctly with 'neutral' and 'negative' identities, (gist memory), specific associations were found to be less accurately remembered when the occupational identity was negative compared to neutral (specific memory). This pattern of results suggests reduced memory specificity for associations containing a negatively valenced component. The encoding of these negative associations was paired with a selective increase in medial prefrontal cortex activity and medial prefrontal-hippocampal connectivity. Individual differences in valence-specific neural connectivity were predictive of valence-specific reduction of memory specificity. The relationship between loss of emotional memory specificity and medial prefrontal-hippocampal connectivity is in line with the hypothesized role of a medial prefrontal-hippocampal circuit in regulating memory specificity, and warrants further investigations in individuals displaying 'overgeneralized' emotional memories.

  7. The noradrenaline-dopamine interaction in the rat medial prefrontal cortex studied by multi-probe microdialysis

    NARCIS (Netherlands)

    Kawahara, H; Kawahara, Y; Westerink, BHC

    2001-01-01

    Multi-probe microdialysis was used to investigate the interaction between the release of noradrenaline and dopamine in the medial prefrontal cortex. Retrograde microdialysis was used to stimulate or inhibit the activity of the locus coeruleus for a restricted period of time, and the response of extr

  8. Medial Prefrontal Cortex Plays a Critical and Selective Role in "Feeling of Knowing" Meta-Memory Judgments

    Science.gov (United States)

    Modirrousta, Mandana; Fellows, Lesley K.

    2008-01-01

    The frontal lobes are thought to play a role in the monitoring of memory performance, or "meta-memory," but the specific circuits involved have yet to be definitively established. Medial prefrontal cortex in general and the anterior cingulate cortex in particular, have been implicated in other forms of monitoring, such as error and conflict…

  9. Temporal Dynamics of Acute Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex and the Protective Effect of Desipramine

    DEFF Research Database (Denmark)

    Nava, Nicoletta; Treccani, Giulia; Alabsi, Abdelrahman;

    2015-01-01

    Stressful events are associated with increased risk of mood disorders. Volumetric reductions have been reported in brain areas critical for the stress response, such as medial prefrontal cortex (mPFC), and dendritic remodeling has been proposed as an underlying factor. Here, we investigated...

  10. Role of the Ventral Medial Prefrontal Cortex in Mediating Behavioral Control-Induced Reduction of Later Conditioned Fear

    Science.gov (United States)

    Baratta, Michael V.; Lucero, Thomas R.; Amat, Jose; Watkins, Linda R.; Maier, Steven F.

    2008-01-01

    A prior experience of behavioral control over a stressor interferes with subsequent Pavlovian fear conditioning, and this effect is dependent on the activation of the ventral medial prefrontal cortex (mPFCv) at the time of the initial experience with control. It is unknown whether mPFCv activity is necessary during fear learning and/or testing for…

  11. Single Prolonged Stress Decreases Glutamate, Glutamine, and Creatine Concentrations In The Rat Medial Prefrontal Cortex

    Science.gov (United States)

    Knox, Dayan; Perrine, Shane A.; George, Sophie A.; Galloway, Matthew P.; Liberzon, Israel

    2010-01-01

    Application of Single Prolonged Stress (SPS) in rats induces changes in neuroendocrine function and arousal that are characteristic of Post Traumatic Stress Disorder (PTSD). PTSD, in humans, is associated with decreased neural activity in the prefrontal cortex, increased neural activity in the amygdala complex, and reduced neuronal integrity in the hippocampus. However, the extent to which SPS models these aspects of PTSD has not been established. In order to address this, we used high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H MRS) ex vivo to assay levels of neurochemicals critical for energy metabolism (creatine and lactate), excitatory (glutamate and glutamine) and inhibitory (gamma amino butyric acid (GABA)) neurotransmission, and neuronal integrity (N-acetyl aspartate (NAA)) in the medial prefrontal cortex (mPFC), amygdala complex, and hippocampus of SPS and control rats. Glutamate, glutamine, and creatine levels were decreased in the mPFC of SPS rats when compared to controls, which suggests decreased excitatory tone in this region. SPS did not alter the neurochemical profiles of either the hippocampus or amygdala. These data suggest that SPS selectively attenuates excitatory tone, without a disruption of neuronal integrity, in the mPFC. PMID:20546834

  12. The medial prefrontal and orbitofrontal cortices differentially regulate dopamine system function.

    Science.gov (United States)

    Lodge, Daniel J

    2011-05-01

    The prefrontal cortex (PFC) is essential for top-down control over higher-order executive function. In this study we demonstrate that the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) differentially regulate VTA dopamine neuron activity, and furthermore, the pattern of activity in the PFC drastically alters the dopamine neuron response. Thus, although single-pulse activation of the mPFC either excites or inhibits equivalent numbers of dopamine neurons, activation of the OFC induces a primarily inhibitory response. Moreover, activation of the PFC with a pattern that mimics spontaneous burst firing of pyramidal neurons produces a strikingly different response. Specifically, burst-like activation of the mPFC induces a massive increase in dopamine neuron firing, whereas a similar pattern of OFC activation largely inhibits dopamine activity. Taken together, these data demonstrate that the mPFC and OFC differentially regulate dopamine neuron activity, and that the pattern of cortical activation is critical for determining dopamine system output.

  13. Agency modulates the lateral and medial prefrontal cortex responses in belief-based decision making.

    Directory of Open Access Journals (Sweden)

    Gui Xue

    Full Text Available Many real-life decisions in complex and changing environments are guided by the decision maker's beliefs, such as her perceived control over decision outcomes (i.e., agency, leading to phenomena like the "illusion of control". However, the neural mechanisms underlying the "agency" effect on belief-based decisions are not well understood. Using functional imaging and a card guessing game, we revealed that the agency manipulation (i.e., either asking the subjects (SG or the computer (CG to guess the location of the winning card not only affected the size of subjects' bets, but also their "world model" regarding the outcome dependency. Functional imaging results revealed that the decision-related activation in the lateral and medial prefrontal cortex (PFC was significantly modulated by agency and previous outcome. Specifically, these PFC regions showed stronger activation when subjects made decisions after losses than after wins under the CG condition, but the pattern was reversed under the SG condition. Furthermore, subjects with high external attribution of negative events were more affected by agency at the behavioral and neural levels. These results suggest that the prefrontal decision-making system can be modulated by abstract beliefs, and are thus vulnerable to factors such as false agency and attribution.

  14. Transcription Profile of Aging and Cognition-Related Genes in the Medial Prefrontal Cortex

    Science.gov (United States)

    Ianov, Lara; Rani, Asha; Beas, Blanca S.; Kumar, Ashok; Foster, Thomas C.

    2016-01-01

    Cognitive function depends on transcription; however, there is little information linking altered gene expression to impaired prefrontal cortex function during aging. Young and aged F344 rats were characterized on attentional set shift and spatial memory tasks. Transcriptional differences associated with age and cognition were examined using RNA sequencing to construct transcriptomic profiles for the medial prefrontal cortex (mPFC), white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging. Age-related gene expression in the mPFC was similar to, though less robust than, changes in the dorsolateral PFC of aging humans suggesting that aging processes may be similar. Importantly, the pattern of transcription associated with aging did not predict cognitive decline. Rather, increased mPFC expression of genes involved in regulation of transcription, including transcription factors that regulate the strength of excitatory and inhibitory inputs, and neural activity-related immediate-early genes was observed in aged animals that exhibit delayed set shift behavior. The specificity of impairment on a mPFC-dependent task, associated with a particular mPFC transcriptional profile indicates that impaired executive function involves altered transcriptional regulation and neural activity/plasticity processes that are distinct from that described for impaired hippocampal function. PMID:27242522

  15. Differential roles of medial prefrontal subregions in the regulation of drug seeking

    Science.gov (United States)

    Moorman, David E.; James, Morgan H.; McGlinchey, Ellen M.; Aston-Jones, Gary

    2014-01-01

    The prefrontal cortex plays an important role in shaping cognition and behavior. Many studies have shown that medial prefrontal cortex (mPFC) plays a key role in seeking, extinction, and reinstatement of cocaine seeking in rodent models of relapse. Subregions of mPFC appear to play distinct roles in these behaviors, such that the prelimbic cortex (PL) is proposed to drive cocaine seeking and the infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction. This dichotomy of mPFC function may be a general attribute, as similar dorsal-ventral distinctions exist for expression vs. extinction of fear conditioning. However, other results indicate that the role of mPFC neurons in reward processing is more complex than a simple PL-seek vs. IL-extinguish dichotomy. Both PL and IL have been shown to drive and inhibit drug seeking (and other types of behaviors) depending on a range of factors including the behavioral context, the drug-history of the animal, and the type of drug investigated. This heterogeneity of findings may reflect multiple subcircuits within each of these PFC areas supporting unique functions. It may also reflect the fact that the mPFC plays a multifaceted role in shaping cognition and behavior, including those overlapping with cocaine seeking and extinction. Here we discuss research leading to the hypothesis that dorsal and ventral mPFC differentially control drug seeking and extinction. We also present recent results calling the absolute nature of a PL vs. IL dichotomy into question. Finally, we consider alternate functions for mPFC that correspond less to response execution and inhibition and instead incorporate the complex cognitive behavior for which the mPFC is broadly appreciated. PMID:25529632

  16. Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex.

    Science.gov (United States)

    Bollinger, Justin L; Bergeon Burns, Christine M; Wellman, Cara L

    2016-02-01

    Susceptibility to stress-linked psychological disorders, including post-traumatic stress disorder and depression, differs between men and women. Dysfunction of medial prefrontal cortex (mPFC) has been implicated in many of these disorders. Chronic stress affects mPFC in a sex-dependent manner, differentially remodeling dendritic morphology and disrupting prefrontally mediated behaviors in males and females. Chronic restraint stress induces microglial activation, reflected in altered microglial morphology and immune factor expression, in mPFC in male rats. Unstressed females exhibit increased microglial ramification in several brain regions compared to males, suggesting both heightened basal activation and a potential for sex-dependent effects of stress on microglial activation. Therefore, we assessed microglial density and ramification in the prelimbic region of mPFC, and immune-associated genes in dorsal mPFC in male and female rats following acute or chronic restraint stress. Control rats were left unstressed. On the final day of restraint, brains were collected for either qPCR or visualization of microglia using Iba-1 immunohistochemistry. Microglia in mPFC were classified as ramified, primed, reactive, or amoeboid, and counted stereologically. Expression of microglia-associated genes (MHCII, CD40, IL6, CX3CL1, and CX3CR1) was also assessed using qPCR. Unstressed females showed a greater proportion of primed to ramified microglia relative to males, alongside heightened CX3CL1-CX3CR1 expression. Acute and chronic restraint stress reduced the proportion of primed to ramified microglia and microglial CD40 expression in females, but did not significantly alter microglial activation in males. This sex difference in microglial activation could contribute to the differential effects of stress on mPFC structure and function in males versus females.

  17. Beyond the Medial Regions of Prefrontal Cortex in the Regulation of Fear and Anxiety.

    Science.gov (United States)

    Shiba, Yoshiro; Santangelo, Andrea M; Roberts, Angela C

    2016-01-01

    Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC) and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC) and orbitofrontal (OFC) regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here, we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies.

  18. Beyond the Medial Regions of Prefrontal Cortex in the Regulation of Fear and Anxiety

    Science.gov (United States)

    Shiba, Yoshiro; Santangelo, Andrea M.; Roberts, Angela C.

    2016-01-01

    Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC) and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC) and orbitofrontal (OFC) regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here, we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies. PMID:26941618

  19. Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution.

    Directory of Open Access Journals (Sweden)

    Hideya Koshino

    Full Text Available BACKGROUND: The anterior prefrontal cortex (PFC exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN, which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. METHODOLOGY/PRINCIPAL FINDINGS: Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition or to ignore them (No face memory condition, then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. CONCLUSIONS/SIGNIFICANCE: The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.

  20. Beyond the medial regions of prefrontal cortex in the regulation of fear and anxiety

    Directory of Open Access Journals (Sweden)

    Yoshiro eShiba

    2016-02-01

    Full Text Available Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC and orbitofrontal (OFC regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies.

  1. Neuronal and inducible nitric oxide synthase upregulation in the rat medial prefrontal cortex following acute restraint stress: A dataset

    Directory of Open Access Journals (Sweden)

    Jereme G. Spiers

    2016-03-01

    Full Text Available This data article provides additional evidence on gene expression changes in the neuronal and inducible isoforms of nitric oxide synthase in the medial prefrontal cortex following acute stress. Male Wistar rats aged 6–8 weeks were exposed to control or restraint stress conditions for up to four hours in the dark cycle after which the brain was removed and the medial prefrontal cortex isolated by cryodissection. Following RNA extraction and cDNA synthesis, gene expression data were measured using quantitative real-time PCR. The mRNA levels of the neuronal and inducible nitric oxide synthase isoforms, and the inhibitory subunit of NF-κB, I kappa B alpha were determined using the ΔΔCT method relative to control animals. This data article presents complementary results related to the research article entitled ‘Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum’ [1].

  2. Neuronal and inducible nitric oxide synthase upregulation in the rat medial prefrontal cortex following acute restraint stress: A dataset.

    Science.gov (United States)

    Spiers, Jereme G; Chen, Hsiao-Jou Cortina; Lee, Johnny K; Sernia, Conrad; Lavidis, Nickolas A

    2016-03-01

    This data article provides additional evidence on gene expression changes in the neuronal and inducible isoforms of nitric oxide synthase in the medial prefrontal cortex following acute stress. Male Wistar rats aged 6-8 weeks were exposed to control or restraint stress conditions for up to four hours in the dark cycle after which the brain was removed and the medial prefrontal cortex isolated by cryodissection. Following RNA extraction and cDNA synthesis, gene expression data were measured using quantitative real-time PCR. The mRNA levels of the neuronal and inducible nitric oxide synthase isoforms, and the inhibitory subunit of NF-κB, I kappa B alpha were determined using the ΔΔCT method relative to control animals. This data article presents complementary results related to the research article entitled 'Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum' [1].

  3. Medial prefrontal dissociations during processing of trait diagnostic and nondiagnostic person information.

    Science.gov (United States)

    Mitchell, Jason P; Cloutier, Jasmin; Banaji, Mahzarin R; Macrae, C Neil

    2006-06-01

    Previous research has suggested that perceivers spontaneously extract trait-specific information from the behaviour of others. However, little is known about whether perceivers spontaneously engage in the same depth of social-cognitive processing for all person information or reserve such processing specifically for information that conveys diagnostic clues about another person's dispositions. Moreover, a question remains as to whether the processing of such nondiagnostic information can be affected by perceivers' explicit goal to consider another's dispositions or not. To examine processing of diagnostic and nondiagnostic social information as a function of perceivers' explicit social-cognitive goals, participants underwent functional magnetic resonance imaging (fMRI) scanning while performing social (impression formation) or non-social orienting tasks using statements that conveyed either diagnostic or nondiagnostic information about the target's personality traits. Replicating two earlier studies, results identified a region of dorsal medial prefrontal cortex (mPFC) that was preferentially activated by impression formation. Interestingly, no difference between trait-diagnostic and nondiagnostic information was observed when participants had the explicit goal of forming an impression, but a substantial effect of diagnosticity emerged when task instructions oriented them away from considering the target as a social agent. These results suggest that trait-nondiagnostic information is not subject to spontaneous social-cognitive processing, but that such processing may nevertheless occur when perceivers have the explicit goal to use that information to form an impression of a target.

  4. Forming impressions of people versus inanimate objects: social-cognitive processing in the medial prefrontal cortex.

    Science.gov (United States)

    Mitchell, Jason P; Neil Macrae, C; Banaji, Mahzarin R

    2005-05-15

    Recent neuroimaging research has linked the task of forming a "person impression" to a distinct pattern of neural activation that includes dorsal regions of the medial prefrontal cortex (mPFC). Although this result suggests the distinctiveness of social cognition - the processes that support inferences about the psychological aspects of other people - it remains unclear whether mPFC contributions to this impression formation task were person specific or if they would extend to other stimulus targets. To address this unresolved issue, participants in the current study underwent fMRI scanning while performing impression formation or a control task for two types of target: other people and inanimate objects. Specifically, participants were asked to use experimentally-provided information either to form an impression of a person or an object or to intentionally encode the sequence in which the information was presented. Results demonstrated that activation in an extensive region of dorsal mPFC was greater for impression formation of other people than for all other trial types, suggesting that this region specifically indexes the social-cognitive aspects of impression formation (i.e., understanding the psychological characteristics of another mental agent). These findings underscore the extent to which social cognition relies on distinct neural mechanisms.

  5. Medial prefrontal cortex acetylcholine injection-induced hypotension: the role of hindlimb vasodilation

    Science.gov (United States)

    Crippa, G. E.; Lewis, S. J.; Johnson, A. K.; Correa, F. M.

    2000-01-01

    The injection of acetylcholine (ACh) into the cingulate region of the medial prefrontal cortex (MPFC) causes a marked fall in arterial blood pressure which is not accompanied by changes in heart rate. The purpose of the present study was to investigate the hemodynamic basis for this stimulus-induced hypotension in Sprague-Dawley rats. The study was designed to determine whether a change in the vascular resistance of hindlimb, renal or mesenteric vascular beds contributes to the fall in arterial pressure in response to ACh injection into the cingulate cortex. Miniature pulsed-Doppler flow probes were used to measure changes in regional blood flow and vascular resistance. The results indicated that the hypotensive response was largely due to a consistent and marked vasodilation in the hindlimb vascular bed. On this basis, an additional experiment was then undertaken to determine the mechanisms that contribute to hindlimb vasodilation. The effect of interrupting the autonomic innervation of one leg on the hindlimb vasodilator response was tested. Unilateral transection of the lumbar sympathetic chain attenuated the cingulate ACh-induced vasodilation in the ipsilateral, but not in the contralateral hindlimb. These results suggest that the hypotensive response to cingulate cortex-ACh injection is caused by skeletal muscle vasodilation mediated by a sympathetic chain-related vasodilator system.

  6. Neural correlates of rules and conflict in medial prefrontal cortex during decision and feedback epochs.

    Science.gov (United States)

    Bissonette, Gregory B; Roesch, Matthew R

    2015-01-01

    The ability to properly adjust behavioral responses to cues in a changing environment is crucial for survival. Activity in the medial Prefrontal Cortex (mPFC) is thought to both represent rules to guide behavior as well as detect and resolve conflicts between rules in changing contingencies. However, while lesion and pharmacological studies have supported a crucial role for mPFC in this type of set-shifting, an understanding of how mPFC represents current rules or detects and resolves conflict between different rules is unclear. Here, we directly address the role of rat mPFC in shifting rule based behavioral strategies using a novel behavioral task designed to tease apart neural signatures of rules, conflict and direction. We demonstrate that activity of single neurons in rat mPFC represent distinct rules. Further, we show increased firing on high conflict trials in a separate population of mPFC neurons. Reduced firing in both populations of neurons was associated with poor performance. Moreover, activity in both populations increased and decreased firing during the outcome epoch when reward was and was not delivered on correct and incorrect trials, respectively. In addition, outcome firing was modulated by the current rule and the degree of conflict associated with the previous decision. These results promote a greater understanding of the role that mPFC plays in switching between rules, signaling both rule and conflict to promote improved behavioral performance.

  7. Depression of excitatory synapses onto parvalbumin interneurons in the medial prefrontal cortex in susceptibility to stress.

    Science.gov (United States)

    Perova, Zinaida; Delevich, Kristen; Li, Bo

    2015-02-18

    In response to extreme stress, individuals either show resilience or succumb to despair. The prefrontal cortex (PFC) is required for coping with stress, and PFC dysfunction has been implicated in stress-related mental disorders, including depression. Nevertheless, the mechanisms by which the PFC participates in stress responses remain unclear. Here, we investigate the role of parvalbumin (PV) interneurons in the medial PFC (mPFC) in shaping behavioral responses to stress induced by the learned helplessness procedure, in which animals are subjected to an unpredictable and inescapable stressor. PV interneurons in the mPFC were probed and manipulated in knock-in mice expressing the Cre recombinase under the endogenous parvalbumin promoter. Notably, we found that excitatory synaptic transmission onto these neurons was decreased in mice showing helplessness, a behavioral state that is thought to resemble features of human depression. Furthermore, selective suppression of PV interneurons in the mPFC using hM4Di, a DREADD (designer receptor exclusively activated by designer drug), promoted helplessness, indicating that activation of these neurons during stress promotes the establishment of resilient behavior. Our results reveal a cellular mechanism of mPFC dysfunction that may contribute to the emergence of maladaptive behavioral responses in the face of adverse life events.

  8. Selective effects of perinatal ethanol exposure in medial prefrontal cortex and nucleus accumbens.

    Science.gov (United States)

    Lawrence, R Charles; Otero, Nicha K H; Kelly, Sandra J

    2012-01-01

    Ethanol exposure during development is the leading known cause of mental retardation and can result in characteristic physiological and cognitive deficits, often termed Fetal Alcohol Spectrum Disorders (FASD). Previous behavioral findings using rat models of FASD have suggested that there are changes in the nucleus accumbens (NAC) and medial prefrontal cortex (mPFC) following ethanol exposure during development. This study used a rat model of FASD to evaluate dendritic morphology in both the NAC and mPFC and cell number in the NAC. Dendritic morphology in mPFC and NAC was assessed using a modified Golgi stain and analyzed via three dimensional reconstructions with Neurolucida (MBF Bioscience). Cell counts in the NAC (shell and core) were determined using an unbiased stereology procedure (Stereo Investigator (MBF Bioscience)). Perinatal ethanol exposure did not affect neuronal or glial cell population numbers in the NAC. Ethanol exposure produced a sexually dimorphic effect on dendritic branching at one point along the NAC dendrites but was without effect on all other measures of dendritic morphology in the NAC. In contrast, spine density was reduced and distribution was significantly altered in layer II/III neurons of the mPFC following ethanol exposure. Ethanol exposure during development was also associated with an increase in soma size in the mPFC. These findings suggest that previously observed sexually dimorphic changes in activation of the NAC in a rat model of FASD may be due to altered input from the mPFC.

  9. Humor Appreciation Involves Parametric and Synchronized Activity in the Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Iidaka, Tetsuya

    2016-10-18

    Humor perception is a ubiquitous phenomenon in human societies. In theories of humor perception, three factors, non-seriousness, social context, and incongruity, have been implicated in humor. In another theory, however, elaboration and reinterpretation of contexts are considered to play a role in eliciting humor. Although the neural correlates of humor appreciation have been investigated using neuroimaging methods, only a few studies have conducted such experiments under natural conditions. In the present study, two functional magnetic resonance imaging experiments, using a comedy movie as a stimulus, were conducted to investigate the neural correlates of humor under natural conditions. The subjects' brain activity was measured while watching and enjoying a movie. In experiment 1, a parametric analysis showed that the medial prefrontal cortex (MPFC) and hippocampus/amygdala had a positive relationship with the subjective rating of funniness. In experiment 2, intersubject correlation was analyzed to investigate synchronized activity across all participants. Signal synchronization that paralleled increased funniness ratings was observed in the MPFC and hippocampus. Thus, it appears that both parametric and synchronized activity in the MPFC and hippocampus are important during humor appreciation. The present study has revealed the brain regions that are predominantly involved in humor sensation under natural condition. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Phasic dopamine release in the medial prefrontal cortex enhances stimulus discrimination.

    Science.gov (United States)

    Popescu, Andrei T; Zhou, Michael R; Poo, Mu-Ming

    2016-05-31

    Phasic dopamine (DA) release is believed to guide associative learning. Most studies have focused on projections from the ventral tegmental area (VTA) to the striatum, and the action of DA in other VTA target regions remains unclear. Using optogenetic activation of VTA projections, we examined DA function in the medial prefrontal cortex (mPFC). We found that mice perceived optogenetically induced DA release in mPFC as neither rewarding nor aversive, and did not change their previously learned behavior in response to DA transients. However, repetitive temporal pairing of an auditory conditioned stimulus (CS) with mPFC DA release resulted in faster learning of a subsequent task involving discrimination of the same CS against unpaired stimuli. Similar results were obtained using both appetitive and aversive unconditioned stimuli, supporting the notion that DA transients in mPFC do not represent valence. Using extracellular recordings, we found that CS-DA pairings increased firing of mPFC neurons in response to CSs, and administration of D1 or D2 DA-receptor antagonists in mPFC during learning impaired stimulus discrimination. We conclude that DA transients tune mPFC neurons for the recognition of behaviorally relevant events during learning.

  11. Stress activates the nucleus incertus and modulates plasticity in the hippocampo-medial prefrontal cortical pathway.

    Science.gov (United States)

    Rajkumar, Ramamoorthy; Wu, You; Farooq, Usman; Tan, Wei Hao; Dawe, Gavin S

    2016-01-01

    The nucleus incertus (NI) is a small cluster of brainstem neurons presumed to play a role in stress responses. We show that swim stress (normal water: 30 min and cold water: 20 min) and elevation stress robustly induced c-Fos expression in the NI and significantly suppressed long-term potentiation (LTP) in the hippocampo-medial prefrontal cortical (HP-mPFC) pathway. To examine whether activation of CRF1 receptors in the NI plays a role in the suppression of HP-mPFC LTP, antalarmin, a specific CRF1 receptor antagonist, was infused directly into the NI either before presentation of (1) elevation stress or (2) high frequency stimulation. As predicted, the intra-NI infusion of antalarmin reversed the elevation stress-induced suppression of LTP in the HP-mPFC pathway. This report suggests that the CRF1 receptor in the NI contributes to stress-related impairment in plasticity of the HP-mPFC pathway. The findings suggest that the NI-HP-mPFC is a stress responsive circuit in the rodent brain.

  12. Valence-based age differences in medial prefrontal activity during impression formation.

    Science.gov (United States)

    Cassidy, Brittany S; Leshikar, Eric D; Shih, Joanne Y; Aizenman, Avigael; Gutchess, Angela H

    2013-01-01

    Reports of age-related changes to medial prefrontal cortex (mPFC) activity during socio-cognitive tasks have shown both age-equivalence and under recruitment. Emotion work illustrates selective mPFC response dependent on valence, such that negative emotional images evoke increased ventral mPFC activity for younger adults, while older adults recruit vmPFC more for positive material. By testing whether this differential age-related response toward valenced material is also present for the social task of forming impressions, we may begin to understand inconsistencies regarding when age differences are present vs. absent in the literature. Using fMRI, participants intentionally formed impressions of positive and negative face-behavior pairs in anticipation of a memory task. Extending previous findings to a social task, valence-based reversals were present in dorsal and ventral mPFC, and posterior cingulate cortex. Younger adults elicited increased activity when forming negative impressions, while older adults had more recruitment when forming positive impressions. This suggests an age-related shift toward emphasizing positive social information may be reflected in the recruitment of regions supporting forming impressions. Overall, the results indicate an age-related shift in neural response to socio-cognitive stimuli that is valence dependent rather than a general age-related reduction in activity, in part informing prior inconsistencies within the literature.

  13. Intracerebroventricular administration of ouabain alters synaptic plasticity and dopamine release in rat medial prefrontal cortex.

    Science.gov (United States)

    Sui, Li; Song, Xiao-Jin; Ren, Jie; Ju, Li-Hua; Wang, Yan

    2013-08-01

    Intracerebroventricular (ICV) administration of ouabain, a specific Na-K-ATPase inhibitor, in rats mimics the manic phenotypes of bipolar disorder and thus has been proposed as one of the best animal models of mania. Bipolar mania has been known to be associated with dysfunctions of medial prefrontal cortex (mPFC), a brain area critically involved in mental functions; however, the exact mechanism underlying these dysfunctions is not yet clear. The present study investigated synaptic transmission, synaptic plasticity, and dopamine release in Sprague-Dawley rat mPFC following ICV administration of ouabain (5 μl of 1 mM ouabain). The electrophysiological results demonstrated that ouabain depressed the short- and the long-term synaptic plasticity, represented by paired-pulse facilitation and long-term potentiation, respectively, in the mPFC. These ouabain-induced alterations in synaptic plasticity can be prevented by pre-treatment with lithium (intraperitoneal injection of 47.5 mg/kg lithium, twice a day, 7 days), which acts as an effective mood stabilizer in preventing mania. The electrochemical results demonstrated that ICV administration of ouabain enhanced dopamine release in the mPFC, which did not be affected by pre-treatment with lithium. These findings suggested that alterations in synaptic plasticity and dopamine release in the mPFC might underlie the dysfunctions of mPFC accompanied with ouabain administration-induced bipolar mania.

  14. Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex.

    Science.gov (United States)

    Campanac, Emilie; Hoffman, Dax A

    2013-06-01

    The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D(2) activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D(2)-receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.

  15. Mechanisms of Functional Hypoconnectivity in the Medial Prefrontal Cortex of Mecp2 Null Mice.

    Science.gov (United States)

    Sceniak, Michael P; Lang, Min; Enomoto, Addison C; Howell, C James; Hermes, Douglas J; Katz, David M

    2016-05-01

    Frontal cortical dysfunction is thought to contribute to cognitive and behavioral features of autism spectrum disorders; however, underlying mechanisms are poorly understood. The present study sought to define how loss of Mecp2, the gene mutated in Rett syndrome (RTT), disrupts function in the murine medial prefrontal cortex (mPFC) using acute brain slices and behavioral testing. Compared with wildtype, pyramidal neurons in the Mecp2 null mPFC exhibit significant reductions in excitatory postsynaptic currents, the duration of excitatory UP-states, evoked population activity, and the ratio of NMDA:AMPA currents, as well as an increase in the relative fraction of NR2B currents. These functional changes are associated with reductions in the density of excitatory dendritic spines, the ratio of vesicular glutamate to GABA transporters and GluN1 expression. In contrast to recent reports on circuit defects in other brain regions, we observed no effect of Mecp2 loss on inhibitory synaptic currents or expression of the inhibitory marker parvalbumin. Consistent with mPFC hypofunction, Mecp2 nulls exhibit respiratory dysregulation in response to behavioral arousal. Our data highlight functional hypoconnectivity in the mPFC as a potential substrate for behavioral disruption in RTT and other disorders associated with reduced expression of Mecp2 in frontal cortical regions.

  16. Striatum-medial prefrontal cortex connectivity predicts developmental changes in reinforcement learning.

    Science.gov (United States)

    van den Bos, Wouter; Cohen, Michael X; Kahnt, Thorsten; Crone, Eveline A

    2012-06-01

    During development, children improve in learning from feedback to adapt their behavior. However, it is still unclear which neural mechanisms might underlie these developmental changes. In the current study, we used a reinforcement learning model to investigate neurodevelopmental changes in the representation and processing of learning signals. Sixty-seven healthy volunteers between ages 8 and 22 (children: 8-11 years, adolescents: 13-16 years, and adults: 18-22 years) performed a probabilistic learning task while in a magnetic resonance imaging scanner. The behavioral data demonstrated age differences in learning parameters with a stronger impact of negative feedback on expected value in children. Imaging data revealed that the neural representation of prediction errors was similar across age groups, but functional connectivity between the ventral striatum and the medial prefrontal cortex changed as a function of age. Furthermore, the connectivity strength predicted the tendency to alter expectations after receiving negative feedback. These findings suggest that the underlying mechanisms of developmental changes in learning are not related to differences in the neural representation of learning signals per se but rather in how learning signals are used to guide behavior and expectations.

  17. Association of familial risk for schizophrenia with thalamic and medial prefrontal functional connectivity during attentional control.

    Science.gov (United States)

    Antonucci, Linda A; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Romano, Raffaella; Quarto, Tiziana; Porcelli, Annamaria; Mancini, Marina; Di Giorgio, Annabella; Caforio, Grazia; Pergola, Giulio; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

    2016-05-01

    Anomalies in behavioral correlates of attentional processing and related brain activity are crucial correlates of schizophrenia and associated with familial risk for this brain disorder. However, it is not clear how brain functional connectivity during attentional processes is key for schizophrenia and linked with trait vs. state related variables. To address this issue, we investigated patterns of functional connections during attentional control in healthy siblings of patients with schizophrenia, who share with probands genetic features but not variables related to the state of the disorder. 356 controls, 55 patients with schizophrenia on stable treatment with antipsychotics and 40 healthy siblings of patients with this brain disorder underwent the Variable Attentional Control (VAC) task during fMRI. Independent Component Analysis (ICA) is allowed to identify independent components (IC) of BOLD signal recorded during task performance. Results indicated reduced connectivity strength in patients with schizophrenia as well as in their healthy siblings in left thalamus within an attentional control component and greater connectivity in right medial prefrontal cortex (PFC) within the so-called Default Mode Network (DMN) compared to healthy individuals. These results suggest a relationship between familial risk for schizophrenia and brain functional networks during attentional control, such that this biological phenotype may be considered a useful intermediate phenotype in order to link genes effects to aspects of the pathophysiology of this brain disorder.

  18. Cross-modal sensory processing in the anterior cingulate and medial prefrontal cortices.

    Science.gov (United States)

    Laurienti, Paul J; Wallace, Mark T; Maldjian, Joseph A; Susi, Christina M; Stein, Barry E; Burdette, Jonathan H

    2003-08-01

    One of the principal functions of the nervous system is to synthesize information from multiple sensory channels into a coherent behavioral and perceptual gestalt. A critical feature of this multisensory synthesis is the sorting and coupling of information derived from the same event. One of the singular features of stimuli conveying such information is their contextual or semantic congruence. Illustrating this fact, subjects are typically faster and more accurate when performing tasks that include congruent compared to incongruent cross-modal stimuli. Using functional magnetic resonance imaging, we demonstrate that activity in select brain areas is sensitive to the contextual congruence among cross-modal cues and to task difficulty. The anterior cingulate gyrus and adjacent medial prefrontal cortices showed significantly greater activity when visual and auditory stimuli were contextually congruent (i.e., matching) than when they were nonmatching. Although activity in these regions was also dependent on task difficulty, showing decreased activity with decreasing task difficulty, the activity changes associated with stimulus congruence predominated.

  19. Efficient learning mechanisms hold in the social domain and are implemented in the medial prefrontal cortex.

    Science.gov (United States)

    Seid-Fatemi, Azade; Tobler, Philippe N

    2015-05-01

    When we are learning to associate novel cues with outcomes, learning is more efficient if we take advantage of previously learned associations and thereby avoid redundant learning. The blocking effect represents this sort of efficiency mechanism and refers to the phenomenon in which a novel stimulus is blocked from learning when it is associated with a fully predicted outcome. Although there is sufficient evidence that this effect manifests itself when individuals learn about their own rewards, it remains unclear whether it also does when they learn about others' rewards. We employed behavioral and neuroimaging methods to address this question. We demonstrate that blocking does indeed occur in the social domain and it does so to a similar degree as observed in the individual domain. On the neural level, activations in the medial prefrontal cortex (mPFC) show a specific contribution to blocking and learning-related prediction errors in the social domain. These findings suggest that the efficiency principle that applies to reward learning in the individual domain also applies to that in the social domain, with the mPFC playing a central role in implementing it.

  20. Lesions to the ventral, but not the dorsal, medial prefrontal cortex enhance latent inhibition.

    Science.gov (United States)

    George, David N; Duffaud, Anaïs M; Pothuizen, Helen H J; Haddon, Josephine E; Killcross, Simon

    2010-04-01

    The acquisition of a conditioned response to a stimulus when it is paired with a reinforcer is retarded if the stimulus has previously been repeatedly pre-exposed in the absence of the reinforcer. This effect, called latent inhibition, has previously been found to be insensitive to lesions of the medial prefrontal cortex (mPFC) in rats. Using an on-baseline conditioned emotional response procedure, which is especially sensitive to small variations in the absolute magnitude of latent inhibition, we found increased latent inhibition following excitotoxic lesions of the mPFC (Experiment 1) or the ventral mPFC alone (Experiment 2) as compared with sham-operated control rats. Lesions restricted to the dorsal mPFC, however, were without effect (Experiment 2). These results are consistent with those of experiments employing another type of interference procedure, extinction. Together, these findings suggest that when different contingencies between a stimulus and a reinforcer are established in separate learning phases, lesions to the ventral mPFC result in increased interference between first-learned and second-learned contingencies. As a consequence, retrieval of the second-learned contingency is impaired, and performance is dominated by the first-learned contingency. These findings are discussed in light of the use of latent inhibition to model cognitive deficits in schizophrenia.

  1. The roles of the medial prefrontal cortex and striatum in reputation processing.

    Science.gov (United States)

    Izuma, Keise; Saito, Daisuke N; Sadato, Norihiro

    2010-01-01

    How we are viewed by other individuals-our reputation-has a considerable influence on our everyday behaviors and is considered an important concept in explaining altruism, a uniquely human trait. Previously it has been proposed that processing one's own reputation requires a reputation representation in the medial prefrontal cortex (mPFC) and a value representation in the striatum. Here, we directly tested this idea using functional magnetic resonance imaging (fMRI). Subjects disclosed their behavioral tendencies with reference to social norms in the presence or absence of other people, a manipulation that is known to greatly affect an individual's concern for their reputation. The mPFC showed strong activation during self-referential processing, and this activity was enhanced by the mere presence of observers. Moreover, the striatum was also strongly activated when subjects responded in front of observers. Thus, the present study demonstrated that the mPFC and striatum were automatically recruited when the task placed a high demand on processing how one is viewed by others. Taken together, our findings suggest that the mPFC and the striatum play a key role in regulating human social behaviors, and these results provide valuable insight into the neural basis of human altruism.

  2. Transcranial magnetic stimulation of medial prefrontal cortex modulates face expressions processing in a priming task.

    Science.gov (United States)

    Mattavelli, G; Cattaneo, Z; Papagno, C

    2011-04-01

    The medial prefrontal cortex (mPFC) and the right somatosensory cortex (rSC) are known to be involved in emotion processing and face expression recognition, although the possibility of segregated circuits for specific emotions in these regions remains unclear. To investigate this issue, we used transcranial magnetic stimulation (TMS) together with a priming paradigm to modulate the activation state of the mPFC and the rSC during emotional expressions discrimination. This novel paradigm allows analyzing how TMS interacts with the ongoing activity of different neuronal populations following prime processing. Participants were asked to discriminate between angry and happy faces that were preceded by a congruent prime (a word expressing the same emotion), an incongruent prime (a word expressing the opposite emotion) or a neutral prime. In TMS trials, a single pulse was delivered over the mPFC, rSC or Vertex (control site) between prime and target presentation. TMS applied over the mPFC significantly affected the priming effect, by selectively increasing response latencies in congruent trials. This indicates that the mPFC contains different neural representations for angry and happy expressions. TMS over rSC did not significantly affect the priming effect, suggesting that rSC is not involved in processing verbal emotional stimuli.

  3. Self-esteem Modulates Medial Prefrontal Cortical Responses to Evaluative Social Feedback

    Science.gov (United States)

    Kelley, William M.; Heatherton, Todd F.

    2010-01-01

    Self-esteem is a facet of personality that influences perception of social standing and modulates the salience of social acceptance and rejection. As such, self-esteem may bias neural responses to positive and negative social feedback across individuals. During functional magnetic resonance imaging scanning, participants (n = 42) engaged in a social evaluation task whereby they ostensibly received feedback from peers indicating they were liked or disliked. Results demonstrated that individuals with low self-esteem believed that they received less positive feedback from others and showed enhanced activity to positive versus negative social feedback in the ventral anterior cingulate cortex/medial prefrontal cortex (vACC/mPFC). By contrast, vACC/mPFC activity was insensitive to positive versus negative feedback in individuals with high self-esteem, and these individuals consistently overestimated the amount of positive feedback received from peers. Voxelwise analyses supported these findings; lower self-esteem predicted a linear increase in vACC/mPFC response to positive versus negative social feedback. Taken together, the present findings propose a functional role for the vACC/mPFC in representing the salience of social feedback and shaping perceptions of relative social standing. PMID:20351022

  4. Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period

    OpenAIRE

    2014-01-01

    The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, b...

  5. Oxytocin in the medial prefrontal cortex is involved in maternal care, maternal aggression and anxiolysis during the postpartum period

    OpenAIRE

    2014-01-01

    The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiolysis. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum...

  6. Modulation of neuronal microcircuit activities within the medial prefrontal cortex by mGluR5 positive allosteric modulator.

    Science.gov (United States)

    Pollard, Marie; Bartolome, Jose Manuel; Conn, P Jeffrey; Steckler, Thomas; Shaban, Hamdy

    2014-10-01

    Suppressing anxiety and fear memory relies on bidirectional projections between the medial prefrontal cortex and the amygdala. Positive allosteric modulators of mGluR5 improve cognition in animal models of schizophrenia and retrieval of newly formed associations such as extinction of fear-conditioned behaviour. The increase in neuronal network activities of the medial prefrontal cortex is influenced by both mGluR1 and mGluR5; however, it is not well understood how they modulate network activities and downstream information processing. To map mGluR5-mediated network activity in relation to its emergence as a viable cognitive enhancer, we tested group I mGluR compounds on medial prefrontal cortex network activity via multi-electrode array neuronal spiking and whole-cell patch clamp recordings. Results indicate that mGluR5 activation promotes feed-forward inhibition that depends on recruitment of neuronal activity by carbachol-evoked up states. The rate of neuronal spiking activity under the influence of carbachol was reduced by the mGluR5 positive allosteric modulator, N-(1,3-Diphenyl-1H-pyrazolo-5-yl)-4-nitrobenzamide (VU-29), and enhanced by the mGluR5 negative allosteric modulator, 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTEP). Spontaneous inhibitory post-synaptic currents were increased upon application of carbachol and in combination with VU-29. These results emphasize a bias towards tonic mGluR5-mediated inhibition that might serve as a signal-to-noise enhancer of sensory inputs projected from associated limbic areas onto the medial prefrontal cortex neuronal microcircuit.

  7. Inactivation of BRD7 results in impaired cognitive behavior and reduced synaptic plasticity of the medial prefrontal cortex.

    Science.gov (United States)

    Xu, Yang; Cao, Wenyu; Zhou, Ming; Li, Changqi; Luo, Yanwei; Wang, Heran; Zhao, Ran; Jiang, Shihe; Yang, Jing; Liu, Yukun; Wang, Xinye; Li, Xiayu; Xiong, Wei; Ma, Jian; Peng, Shuping; Zeng, Zhaoyang; Li, Xiaoling; Tan, Ming; Li, Guiyuan

    2015-06-01

    BRD7 is a bromodomain-containing protein (BCP), and recent evidence implicates the role of BCPs in the initiation and development of neurodevelopmental disorders. However, few studies have investigated the biological functions of BRD7 in the central nervous system. In our study, BRD7 was found to be widely expressed in various regions of the mouse brain, including the medial prefrontal cortex (mPFC), caudate putamen (CPu), hippocampus (Hip), midbrain (Mb), cerebellum (Cb), and mainly co-localized with neuron but not with glia. Using a BRD7 knockout mouse model and a battery of behavioral tests, we report that disruption of BRD7 results in impaired cognitive behavior leaving the emotional behavior unaffected. Moreover, a series of proteins involved in synaptic plasticity were decreased in the medial prefrontal cortex and there was a concomitant decrease in neuronal spine density and dendritic branching in the medial prefrontal cortex. However, no significant difference was found in the hippocampus compared to the wild-type mice. Thus, BRD7 might play a critical role in the regulation of synaptic plasticity and affect cognitive behavior.

  8. Childhood emotional maltreatment severity is associated with dorsal medial prefrontal cortex responsivity to social exclusion in young adults.

    Science.gov (United States)

    van Harmelen, Anne-Laura; Hauber, Kirsten; Gunther Moor, Bregtje; Spinhoven, Philip; Boon, Albert E; Crone, Eveline A; Elzinga, Bernet M

    2014-01-01

    Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment.

  9. The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats.

    Science.gov (United States)

    Willcocks, Andrea L; McNally, Gavan P

    2013-01-01

    The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation.

  10. The roles of the medial prefrontal cortex and hippocampus in a spatial paired-association task.

    Science.gov (United States)

    Lee, Inah; Solivan, Frances

    2008-05-01

    Although the roles of both the hippocampus and the medial prefrontal cortex (mPFC) have been suggested in a spatial paired-associate memory task, both areas were investigated separately in prior studies. The current study investigated the relative contributions of the hippocampus and mPFC to spatial paired-associate learning within a single behavioral paradigm. In a novel behavioral task, a pair of different objects appeared repeatedly across trials, but in different arms in a radial maze, and different rules were associated with those arms for reward. Specifically, in an "object-in-place" arm, the rat was required to choose a particular object associated with the arm. In a "location-in-place" arm, the animal was required to choose a certain within-arm location (ignoring the object occupying the location). Compared to normal animals, rats with ibotenic acid-based lesions in the hippocampus showed an irrecoverable impairment in performance in both object-in-place and location-in-place arms. When the mPFC was inactivated by muscimol (GABA(A) receptor agonist) in the normal animals with intact hippocampi, they showed the same severe impairment as seen in the hippocampal lesioned rats only in object-in-place arms. The results confirm that the hippocampus is necessary for a biconditional paired-associate task when space is a critical component. The mPFC, however, is more selectively involved in the object-place paired-associate task than in the location-place paired-associate task. The current task powerfully demonstrates an experimental situation in which both the hippocampus and mPFC are required and may serve as a useful paradigm for investigating the neural mechanisms of object-place association.

  11. Effect of excitotoxic lesions of rat medial prefrontal cortex on spatial memory.

    Science.gov (United States)

    Lacroix, Laurent; White, Ilsun; Feldon, Joram

    2002-06-15

    The involvement of medial prefrontal cortex (mPFC) in spatial learning was examined in two memory tasks using spatial components, the Morris water maze and the three-panel runway. Using the Morris water maze task, with an invisible platform, the effects of NMDA mPFC lesions were assessed in a procedure reflecting spatial learning and memory, including a spatial reversal. In the three-panel runway, a delayed matching-to-position procedure was used in which rats were required to find food at the end of the runway after passing through one of three panel gates set into four barriers spaced equally apart along the maze. In addition, mPFC lesions were assessed behaviorally in two behavioral tests known to be sensitive to mPFC dysfunction: the food hoarding paradigm and spontaneous locomotion in the open field. Consistent with the documented effects of mPFC damage, NMDA mPFC lesions impaired food hoarding behavior and increased spontaneous exploratory locomotion. In the Morris water maze and the three-panel runway, mPFC-lesioned rats showed relatively few effects, supporting the conclusion that the damage inflicted to the mPFC had no consequence for the processing of spatial information. However, mPFC lesioned animals showed slower acquisition during both the training trial in the three-panel runway and the reversal training in the Morris water maze. These results suggest that spatial memory did not depend on mPFC integrity in the Morris water maze and the three-panel runway experiments, and address the issue of deficits induced by mPFC lesions in memory tasks dependent on non-mnemonic processes such as attentional processes and/or a reduced behavioral flexibility to environmental changes.

  12. Chronic alcohol disrupts dopamine receptor activity and the cognitive function of the medial prefrontal cortex.

    Science.gov (United States)

    Trantham-Davidson, Heather; Burnett, Elizabeth J; Gass, Justin T; Lopez, Marcelo F; Mulholland, Patrick J; Centanni, Samuel W; Floresco, Stan B; Chandler, L Judson

    2014-03-05

    Dopamine (DA) receptors in the medial prefrontal cortex (mPFC) exert powerful effects on cognition by modulating the balance between excitatory and inhibitory neurotransmission. The present study examined the impact of chronic intermittent ethanol (CIE) exposure on cognitive function and DA receptor-mediated neurotransmission in the rat mPFC. Consistent with alterations in executive function in alcoholics, CIE-exposed rats exhibited deficits in behavioral flexibility in an operant set-shifting task. Since alterations in dopaminergic neurotransmission in the mPFC have been implicated in a number of behavioral disorders including addiction, studies were then performed in the adult acute slice preparation to examine changes in DA receptor function in the mPFC following CIE exposure. In slices obtained from control rats, DA receptor stimulation was observed to exert complex actions on neuronal firing and synaptic neurotransmission that were not only dependent upon the particular receptor subtype but also whether it was a pyramidal cell or a fast-spiking interneuron. In contrast to slices from control rats, there was a near complete loss of the modulatory actions of D2/D4 receptors on cell firing and neurotransmission in slices obtained immediately, 1 and 4 weeks after the last day of CIE exposure. This loss did not appear to be associated with changes in receptor expression. In contrast, CIE exposure did not alter D1 receptor function or mGluR1 modulation of firing. These studies are consistent with the suggestion that chronic alcohol exposure disrupts cognitive function at least in part through disruption of D2 and D4 receptor signaling in mPFC.

  13. Oxytocin blurs the self-other distinction during trait judgments and reduces medial prefrontal cortex responses.

    Science.gov (United States)

    Zhao, Weihua; Yao, Shuxia; Li, Qin; Geng, Yayuan; Ma, Xiaole; Luo, Lizhu; Xu, Lei; Kendrick, Keith M

    2016-07-01

    The neuropeptide oxytocin (OXT) may act either to increase or blur the distinction between self and other and thereby promote either more selfish or altruistic behaviors. To attempt to distinguish between these two possibilities we performed a double-blind, between-subject, placebo-controlled design study to investigate the effect of intranasal OXT on self and other (mother, classmate, or stranger) trait judgments in conjunction with functional magnetic resonance imaging. Results showed that OXT reduced response times for making both self and other judgments, but also reduced the accuracy of their subsequent recall, thereby abolishing the normal self-bias observed in this task. OXT also abolished the positive correlation between response and self-esteem scale scores seen in the PLC group, suggesting that its effects were strongest in individuals with higher levels of self-esteem. A whole-brain functional magnetic resonance imaging analysis revealed that OXT also reduced responses during both self and other trait judgments in the dorsal (dmPFC) and ventral (vmPFC) medial prefrontal cortex. A subsequent region of interest analysis revealed that behavioral performance and self-esteem scale scores were associated with dmPFC activation and its functional connectivity with the anterior cingulate and between the vmPFC and posterior cingulate. Thus overall, while OXT may improve speed of decision making in self -vs. other trait judgments it also blunts the normal bias towards remembering self-attributes and reduces mPFC responses and connectivity with other cortical midline regions involved in self-processing. This is consistent with the view that OXT can reduce self-centered behavior. Hum Brain Mapp 37:2512-2527, 2016. © 2016 Wiley Periodicals, Inc.

  14. The Role of the Medial Prefrontal Cortex in the Generalization of Conditioned Fear.

    Science.gov (United States)

    Spalding, Kelsey N

    2017-08-31

    Fear generalization, the generalization of fear to innocuous stimuli, is a characteristic component of pathological anxiety. Neural models of fear generalization suggest the involvement of the medial prefrontal cortex (mPFC). However, conflicting empirical findings complicate our understanding of the role of the mPFC in pathological anxiety. To address important unanswered questions in this area, a detailed review and synthesis of results from human and nonhuman animal investigations of conditioned fear generalization was conducted. Empirical articles were identified through March 2017 and selected if they used fear conditioning, measured fear generalization, and included a measure of activity in the mPFC or manipulation of mPFC functioning. In human cued fear conditioning, the ventral mPFC plays an important role in the inhibition of fear generalization, whereas dorsal mPFC is important for the activation of generalized fear. This pattern remains to be further investigated in nonhuman animal models. Nonhuman animal research suggests an interaction between the neural correlates of contextual fear generalization and timing, such that the mPFC appears to increase fear generalization at remote time points and reduce generalization at recent time points following acquisition. The literature suggests a key role for the mPFC in fear generalization, but empirical details vary depending on specific regions within the mPFC, the animal model used, and the timing of the generalization test. Further research is needed to elucidate the role of the mPFC in fear generalization, which could in turn facilitate more effective pharmacological interventions for pathological anxiety. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Elevated dopamine in the medial prefrontal cortex suppresses cocaine seeking via D1 receptor overstimulation.

    Science.gov (United States)

    Devoto, Paola; Fattore, Liana; Antinori, Silvia; Saba, Pierluigi; Frau, Roberto; Fratta, Walter; Gessa, Gian Luigi

    2016-01-01

    Previous investigations indicate that the dopamine-β-hydroxylase (DBH) inhibitors disulfiram and nepicastat suppress cocaine-primed reinstatement of cocaine self-administration behaviour. Moreover, both inhibitors increase dopamine release in the rat medial prefrontal cortex (mPFC) and markedly potentiate cocaine-induced dopamine release in this region. This study was aimed to clarify if the suppressant effect of DBH inhibitors on cocaine reinstatement was mediated by the high extracellular dopamine in the rat mPFC leading to a supra-maximal stimulation of D1 receptors in the dorsal division of mPFC, an area critical for reinstatement of cocaine-seeking behaviour. In line with previous microdialysis studies in drug-naïve animals, both DBH inhibitors potentiated cocaine-induced dopamine release in the mPFC, in the same animals in which they also suppressed reinstatement of cocaine seeking. Similar to the DBH inhibitors, L-DOPA potentiated cocaine-induced dopamine release in the mPFC and suppressed cocaine-induced reinstatement of cocaine-seeking behaviour. The bilateral microinfusion of the D1 receptor antagonist SCH 23390 into the dorsal mPFC not only prevented cocaine-induced reinstatement of cocaine seeking but also reverted both disulfiram- and L-DOPA-induced suppression of reinstatement. Moreover, the bilateral microinfusion of the D1 receptor agonist chloro-APB (SKF 82958) into the dorsal mPFC markedly attenuated cocaine-induced reinstatement of cocaine seeking. These results suggest that stimulation of D1 receptors in the dorsal mPFC plays a crucial role in cocaine-induced reinstatement of cocaine seeking, whereas the suppressant effect of DBH inhibitors and L-DOPA on drug-induced reinstatement is mediated by a supra-maximal stimulation of D1 receptors leading to their inactivation.

  16. Increased neuronal firing in resting and sleep in areas of the macaque medial prefrontal cortex.

    Science.gov (United States)

    Gabbott, Paul L; Rolls, Edmund T

    2013-06-01

    The medial prefrontal cortex (mPFC) of humans and macaques is an integral part of the default mode network and is a brain region that shows increased activation in the resting state. A previous paper from our laboratory reported significantly increased firing rates of neurons in the macaque subgenual cingulate cortex, Brodmann area (BA) 25, during disengagement from a task and also during slow wave sleep [E.T. Rolls et al. (2003) J. Neurophysiology, 90, 134-142]. Here we report the finding that there are neurons in other areas of mPFC that also increase their firing rates during disengagement from a task, drowsiness and eye-closure. During the neurophysiological recording of single mPFC cells (n = 249) in BAs 9, 10, 13 m, 14c, 24b and especially pregenual area 32, populations of neurons were identified whose firing rates altered significantly with eye-closure compared with eye-opening. Three types of neuron were identified: Type 1 cells (28.1% of the total population) significantly increased (mean + 329%; P ≪ 0.01) their average firing rate with eye-closure, from 3.1 spikes/s when awake to 10.2 spikes/s when asleep; Type 2 cells (6.0%) significantly decreased (mean -68%; P areas of mPFC, implicated in the anterior default mode network, there is a substantial population of neurons that significantly increase their firing rates during periods of eye-closure. Such neurons may be part of an interconnected network of distributed brain regions that are more active during periods of relaxed wakefulness than during attention-demanding tasks. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  17. Positively valenced stimuli facilitate creative novel metaphoric processes by enhancing medial prefrontal cortical activation.

    Science.gov (United States)

    Subramaniam, Karuna; Beeman, Mark; Faust, Miriam; Mashal, Nira

    2013-01-01

    A metaphor is a figure of speech in which a subject is symbolic of another unrelated object. In the present study, we examined neural patterns associated with both novel unfamiliar and conventional familiar metaphoric processing, and how these patterns are modulated by affective valence. Prior to fMRI scanning, participants received a list of word pairs (novel unfamiliar metaphors as well as conventional familiar metaphors) and were asked to denote the valence (positive, negative, or neutral) of each word pair. During scanning, participants had to decide whether the word pairs formed meaningful or meaningless expressions. Results indicate that participants were faster and more accurate at deciding that positively valenced metaphors were meaningful compared to neutral metaphors. These behavioral findings were accompanied by increased activation in the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and the right inferior parietal lobe (RIPL). Specifically, positively valenced novel unfamiliar metaphors elicited activation in these brain regions in addition to the left superior temporal gyrus when compared to neutral novel metaphors. We also found that the mPFC and PCC mediated the processing of positively valenced metaphors when compared to negatively valenced metaphors. Positively valenced conventional metaphors, however, elicited different neural signatures when contrasted with either neutral or negatively valenced conventional metaphors. Together, our results indicate that positively valenced stimuli facilitate creative metaphoric processes (specifically novel metaphoric processes) by mediating attention and cognitive control processes required for the access, integration, and selection of semantic associations via modulation of the mPFC. The present study is important for the development of neural accounts of emotion-cognition interactions required for creativity, language, and successful social functioning in general.

  18. Catecholaminergic depletion within the prelimbic medial prefrontal cortex enhances latent inhibition.

    Science.gov (United States)

    Nelson, A J D; Thur, K E; Marsden, C A; Cassaday, H J

    2010-09-29

    Latent inhibition (LI) refers to the reduction in conditioning to a stimulus that has received repeated non-reinforced pre-exposure. Investigations into the neural substrates of LI have focused on the nucleus accumbens (NAc) and its inputs from the hippocampal formation and adjacent cortical areas. Previous work has suggested that lesions to the medial prefrontal cortex (mPFC), another major source of input to the NAc, do not disrupt LI. However, a failure to observe disrupted LI does not preclude the possibility that a particular brain region is involved in the expression of LI. Moreover, the mPFC is a heterogeneous structure and there has been no investigation of a possible role of different regions within the mPFC in regulating LI under conditions that prevent LI in controls. Here, we tested whether 6-hydroxydopamine (6-OHDA)-induced lesions of dopamine (DA) terminals within the prelimbic (PL) and infralimbic (IL) mPFC would lead to the emergence of LI under conditions that do produce LI in controls (weak pre-exposure). LI was measured in a thirst motivated conditioned emotional response procedure with 10 pre-exposures to a noise conditioned stimulus (CS) and two conditioning trials. Sham-operated and IL-lesioned animals did not show LI and conditioned to the pre-exposed CS at comparable levels to the non-pre-exposed controls. 6-OHDA lesions to the PL, however, produced potentiation of LI. These results provide the first demonstration that the PL mPFC is a component of the neural circuitry underpinning LI.

  19. Frequency-Dependent Representation of Reinforcement-Related Information in the Human Medial and Lateral Prefrontal Cortex.

    Science.gov (United States)

    Smith, Elliot H; Banks, Garrett P; Mikell, Charles B; Cash, Syndey S; Patel, Shaun R; Eskandar, Emad N; Sheth, Sameer A

    2015-12-01

    The feedback-related negativity (FRN) is a commonly observed potential in scalp electroencephalography (EEG) studies related to the valence of feedback about a subject's performance. This potential classically manifests as a negative deflection in medial frontocentral EEG contacts following negative feedback. Recent work has shown prominence of theta power in the spectral composition of the FRN, placing it within the larger class of "frontal midline theta" cognitive control signals. Although the dorsal anterior cingulate cortex (dACC) is thought to be the cortical generator of the FRN, conclusive data regarding its origin and propagation are lacking. Here we examine intracranial electrophysiology from the human medial and lateral prefrontal cortex (PFC) to better understand the anatomical localization and communication patterns of the FRN. We show that the FRN is evident in both low- and high-frequency local field potentials (LFPs) recorded on electrocorticography. The FRN is larger in medial compared with lateral PFC, and coupling between theta band phase and high-frequency LFP power is also greater in medial PFC. Using Granger causality and conditional mutual information analyses, we provide evidence that feedback-related information propagates from medial to lateral PFC, and that this information transfer oscillates with theta-range periodicity. These results provide evidence for the dACC as the cortical source of the FRN, provide insight into the local computation of frontal midline theta, and have implications for reinforcement learning models of cognitive control.

  20. Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery

    Science.gov (United States)

    Goldwater, Deena S.; Pavlides, Constantine; Hunter, Richard G.; Bloss, Erik B.; Hof, Patrick R.; McEwen, Bruce S.; Morrison, John H.

    2009-01-01

    Chronic stress has been shown in animal models to result in altered dendritic morphology of pyramidal neurons of the medial prefrontal cortex (mPFC). It has been hypothesized that the stress-induced dendritic retractions and spine loss lead to disrupted connectivity that results in stress-induced functional impairment of mPFC. While these alterations were initially viewed as a neurodegenerative event, it has recently been established that stress induced dendritic alterations are reversible if animals are given time to recover from chronic stress. However, whether spine growth accompanies dendritic extension remains to be demonstrated. It is also not known if recovery-phase dendritic extension allows for re-establishment of functional capacity. The goal of this study, therefore, was to characterize the structural and functional effects of chronic stress and recovery on the infralimbic (IL) region of the rat mPFC. We compared neuronal morphology of layer V IL pyramidal neurons from animals subjected to 21 days of chronic restraint stress (CRS) to those that experienced CRS followed by a 21 day recovery period. Layer V pyramidal cell functional capacity was assessed by intra-IL long-term potentiation (LTP) both in the absence and presence of SKF38393, a dopamine receptor partial agonist and a known PFC LTP modulator. We found that stress-induced IL apical dendritic retraction and spine loss co-occur with receptor-mediated impairments to catecholaminergic facilitation of synaptic plasticity. We also found that while post-stress recovery did not reverse distal dendritic retraction, it did result in over-extension of proximal dendritic neuroarchitecture and spine growth as well as a full reversal of CRS-induced impairments to catecholaminergic-mediated synaptic plasticity. Our results support the hypothesis that disease-related PFC dysfunction is a consequence of network disruption secondary to altered structural and functional plasticity and that circuitry

  1. Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats

    OpenAIRE

    2014-01-01

    The neuropeptide oxytocin (OT) has anxiolytic effects in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a targ...

  2. Medial prefrontal cortex involvement in the expression of extinction and ABA renewal of instrumental behavior for a food reinforcer.

    Science.gov (United States)

    Eddy, Meghan C; Todd, Travis P; Bouton, Mark E; Green, John T

    2016-02-01

    Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of

  3. Medial Prefrontal Cortex Involvement in the Expression of Extinction and ABA Renewal of Instrumental Behavior for a Food Reinforcer

    Science.gov (United States)

    Eddy, Meghan C.; Todd, Travis P.; Bouton, Mark E.; Green, John T.

    2015-01-01

    Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of

  4. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    Science.gov (United States)

    Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

  5. Lipopolysaccharide increases degradation of central monoamines: an in vivo microdialysis study in the nucleus accumbens and medial prefrontal cortex of mice.

    Science.gov (United States)

    van Heesch, Floor; Prins, Jolanda; Konsman, Jan Pieter; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Rybka, Joanna; Olivier, Berend; Kraneveld, Aletta D; Korte, S Mechiel

    2014-02-15

    Peripheral administration of lipopolysaccharide (LPS) in rodents induces anhedonia, i.e. the inability to experience pleasure. Recently, we reported that serotonin transporter (SERT) function is required for LPS-induced anhedonia. Less is known about the effect of LPS on the biological activity of dopamine transporters (DAT) and norepinephrine transporters (NET). Therefore, in vivo microdialysis was performed in the nucleus accumbens and medial prefrontal cortex of C57BL6/J mice exposed to saline or LPS (133 µg/kg i.p.). To investigate the possible involvement of different monoamine transporters, the triple reuptake inhibitor DOV 216,303 or saline was i.p. injected 30 min before the saline/LPS injection. The dose of LPS, shown to decrease responding for brain stimulation reward in mice, significantly increased extracellular levels of monoamine metabolites (5-HIAA, DOPAC and HVA) in the nucleus accumbens and medial prefrontal cortex. Remarkably, DOV 216,303 abolished LPS-induced DOPAC and HVA formation in the nucleus accumbens, suggesting that LPS increases DAT activity in this brain area. DOV 216,303 also inhibited LPS-induced DOPAC and HVA formation in the medial prefrontal cortex. Since DAT density is very low in this brain structure, reuptake of DA predominantly takes place via NET, suggesting that LPS increases DAT and NET activity in the medial prefrontal cortex. Furthermore, DOV 216,303 pretreatment prevented LPS-induced 5-HIAA formation only in the medial prefrontal cortex, indicating that LPS increases prefrontal SERT activity. In conclusion, the present findings suggest that peripheral LPS increases DAT activity in the nucleus accumbens and increases NET and SERT activity in the medial prefrontal cortex of mice.

  6. Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus.

    Science.gov (United States)

    Evuarherhe, Obaro; Barker, Gareth R I; Savalli, Giorgia; Warburton, Elizabeth C; Brown, Malcolm W

    2014-08-01

    Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. © 2014 Wiley Periodicals, Inc.

  7. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

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    Irit Akirav

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  8. Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex

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    Tariq Waseem Chohan

    2014-09-01

    Full Text Available Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1 and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET and wild-type (WT mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV and the dentate gyrus (DG of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.

  9. Chronic infusions of GABA into the medial prefrontal cortex induce spatial alternation deficits in aged rats.

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    Meneses, S; Galicia, O; Brailowsky, S

    1993-10-21

    It has been proposed that functions associated with the prefrontal cortex could change as a consequence of aging. Previous experiments in young rats have demonstrated that anatomical lesions or chronic GABA infusions into this area produce deficits in spatial delayed alternation tasks. The present study examines the effect of chronic (7 days) GABA or saline infusion into the prefrontal cortex on the performance of delayed alternation task in old rats (24 months). The results suggested that aged rats needed more sessions to acquire the delayed alternation task. GABA infusions into the prefrontal cortex produced deficits in spatial alternation tasks similar to those previously observed in young rats. Performance rapidly recovered after the infusion period. Histological analysis showed similar lesion size in both groups. The results suggest that aged prefrontal cortex and/or related areas participating in the acquisition of the delayed alternation task are more sensitive to aging processes. Furthermore, the prefrontal cortex is important for the retention of a previously learned spatial delayed alternation task. The structures involved in functional recovery from these deficits appear to be fully functional in aged rats.

  10. Medial prefrontal cortex lesions impair decision-making on a rodent gambling task: reversal by D1 receptor antagonist administration.

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    Paine, Tracie A; Asinof, Samuel K; Diehl, Geoffrey W; Frackman, Anna; Leffler, Joseph

    2013-04-15

    Decision-making is a complex cognitive process that is impaired in a number of psychiatric disorders. In the laboratory, decision-making is frequently assessed using "gambling" tasks that are designed to simulate real-life decisions in terms of uncertainty, reward and punishment. Here, we investigate whether lesions of the medial prefrontal cortex (PFC) cause impairments in decision-making using a rodent gambling task (rGT). In this task, rats have to decide between 1 of 4 possible options: 2 options are considered "advantageous" and lead to greater net rewards (food pellets) than the other 2 "disadvantageous" options. Once rats attained stable levels of performance on the rGT they underwent sham or excitoxic lesions of the medial PFC and were allowed to recover for 1 week. Following recovery, rats were retrained for 5 days and then the effects of a dopamine D1-like receptor antagonist (SCH23390) or a D2-like receptor antagonist (haloperidol) on performance were assessed. Lesioned rats exhibited impaired decision-making: they made fewer advantageous choices and chose the most optimal choice less frequently than did sham-operated rats. Administration of SCH23390 (0.03 mg/kg), but not haloperidol (0.015-0.03 mg/kg) attenuated the lesion-induced decision-making deficit. These results indicate that the medial PFC is important for decision-making and that excessive signaling at D1 receptors may contribute to decision-making impairments.

  11. Medial prefrontal cortex inversely regulates toluene-induced changes in markers of synaptic plasticity of mesolimbic dopamine neurons

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    Beckley, Jacob T.; Evins, Caitlin E.; Fedarovich, Hleb; Gilstrap, Meghin J.; Woodward, John J.

    2013-01-01

    Toluene is a volatile solvent that is intentionally inhaled by children, adolescents and adults for its intoxicating effects. While voluntary use of toluene suggests that it possesses rewarding properties and abuse potential, it is unknown whether toluene alters excitatory synaptic transmission in reward sensitive dopamine neurons like other drugs of abuse. Here, using a combination of retrograde labeling and slice electrophysiology, we show that a brief in vivo exposure of rats to a behaviorally relevant concentration of toluene vapor enhances glutamatergic synaptic strength of dopamine (DA) neurons projecting to nucleus accumbens core and medial shell neurons. This effect persisted for up to 3 days in mesoaccumbens core DA neurons and for at least 21 days in those projecting to the medial shell. In contrast, toluene vapor exposure had no effect on synaptic strength of DA neurons that project to the medial prefrontal cortex (mPFC). Furthermore, infusion of GABAergic modulators into the mPFC prior to vapor exposure to pharmacologically manipulate output, inhibited or potentiated toluene's action on mesoaccumbens DA neurons. Taken together, the results of these studies indicate that toluene induces a target-selective increase in mesolimbic DA neuron synaptic transmission and strongly implicates the mPFC as an important regulator of drug-induced plasticity of mesolimbic dopamine neurons. PMID:23303956

  12. Anticipatory activity in rat medial prefrontal cortex during a working memory task

    Institute of Scientific and Technical Information of China (English)

    Wenwen Bai; Tiaotiao Liu; Hu Yi; Shuangyan Li; Xin Tian

    2012-01-01

    Objective Working memory is a key cognitive function in which the prefrontal cortex plays a crucial role.This study aimed to show the firing patterns of a neuronal population in the prefrontal cortex of the rat in a working memory task and to explore how a neuronal ensemble encodes a working memory event.Methods Sprague-Dawley rats were trained in a Y-maze until they reached an 80% correct rate in a working memory task.Then a 16-channel microelectrode array was implanted in the prefrontal cortex.After recovery,neuronal population activity was recorded during the task,using the Cerebus data-acquisition system.Spatio-temporal trains of action potentials were obtained from the original neuronal population signals.Results During the Y-maze working memory task,some neurons showed significantly increased firing rates and evident neuronal ensemble activity.Moreover,the anticipatory activity was associated with the delayed alternate choice of the upcoming movement.In correct trials,the averaged pre-event firing rate (10.86 ± 1.82 spikes/bin) was higher than the post-event rate (8.17 ± 1.15 spikes/bin) (P <0.05).However,in incorrect trials,the rates did not differ.Conclusion The results indicate that the anticipatory activity of a neuronal ensemble in the prefrontal cortex may play a role in encoding working memory events.

  13. Deconstructing the brain’s moral network: dissociable functionality between the temporoparietal junction and ventro-medial prefrontal cortex

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    Mobbs, Dean; Dalgleish, Tim

    2014-01-01

    Research has illustrated that the brain regions implicated in moral cognition comprise a robust and broadly distributed network. However, understanding how these brain regions interact and give rise to the complex interplay of cognitive processes underpinning human moral cognition is still in its infancy. We used functional magnetic resonance imaging to examine patterns of activation for ‘difficult’ and ‘easy’ moral decisions relative to matched non-moral comparators. This revealed an activation pattern consistent with a relative functional double dissociation between the temporoparietal junction (TPJ) and ventro-medial prefrontal cortex (vmPFC). Difficult moral decisions activated bilateral TPJ and deactivated the vmPFC and OFC. In contrast, easy moral decisions revealed patterns of activation in the vmPFC and deactivation in bilateral TPJ and dorsolateral PFC. Together these results suggest that moral cognition is a dynamic process implemented by a distributed network that involves interacting, yet functionally dissociable networks. PMID:23322890

  14. Deconstructing the brain's moral network: dissociable functionality between the temporoparietal junction and ventro-medial prefrontal cortex.

    Science.gov (United States)

    Feldmanhall, Oriel; Mobbs, Dean; Dalgleish, Tim

    2014-03-01

    Research has illustrated that the brain regions implicated in moral cognition comprise a robust and broadly distributed network. However, understanding how these brain regions interact and give rise to the complex interplay of cognitive processes underpinning human moral cognition is still in its infancy. We used functional magnetic resonance imaging to examine patterns of activation for 'difficult' and 'easy' moral decisions relative to matched non-moral comparators. This revealed an activation pattern consistent with a relative functional double dissociation between the temporoparietal junction (TPJ) and ventro-medial prefrontal cortex (vmPFC). Difficult moral decisions activated bilateral TPJ and deactivated the vmPFC and OFC. In contrast, easy moral decisions revealed patterns of activation in the vmPFC and deactivation in bilateral TPJ and dorsolateral PFC. Together these results suggest that moral cognition is a dynamic process implemented by a distributed network that involves interacting, yet functionally dissociable networks.

  15. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

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    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  16. Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats.

    Science.gov (United States)

    Li, Zhen; Lu, Yun-Fei; Li, Chun-Li; Wang, Yan; Sun, Wei; He, Ting; Chen, Xue-Feng; Wang, Xiao-Liang; Chen, Jun

    2014-07-01

    Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception.

  17. Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus.

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    Maximiliano Rapanelli

    Full Text Available Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC and the hippocampus (HIPP during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and

  18. NR2A- and NR2B-Containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

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    Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

    2013-01-01

    Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…

  19. Regionally Selective Requirement for D[subscript 1]/D[subscript 5] Dopaminergic Neurotransmission in the Medial Prefrontal Cortex in Object-in-Place Associative Recognition Memory

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    Savalli, Giorgia; Bashir, Zafar I.; Warburton, E. Clea

    2015-01-01

    Object-in-place (OiP) memory is critical for remembering the location in which an object was last encountered and depends conjointly on the medial prefrontal cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine D[subscript 1]/D[subscript 5] receptor neurotransmission within these brain regions for OiP memory. Bilateral…

  20. NR2A- and NR2B-Containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

    Science.gov (United States)

    Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

    2013-01-01

    Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…

  1. β-Adrenergic receptor agonist increases voltage-gated Na(+) currents in medial prefrontal cortex pyramidal neurons.

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    Szulczyk, Bartlomiej

    2015-05-19

    The prefrontal cortex does not function properly in neuropsychiatric diseases and during chronic stress. The aim of this study was to test the effects of isoproterenol, a β-adrenergic receptor agonist, on the voltage-dependent fast-inactivating Na(+) currents in medial prefrontal cortex (mPFC) pyramidal neurons obtained from young rats. The recordings were performed in the cell-attached configuration. Isoproterenol (2μM) did not change the peak Na(+) current amplitude but shifted the IV curve of the Na(+) currents toward hyperpolarization. Pretreatment of the cells with the β-adrenergic antagonists propranolol and metoprolol abolished the effect of isoproterenol on the Na(+) currents, suggesting the involvement of β1-adrenergic receptors. The effect of β-adrenergic receptor stimulation on the sodium currents was dependent on kinase A and kinase C; the effect was diminished in the presence of the kinase A antagonist H-89 and the kinase C antagonist chelerythrine and abolished when the antagonists were coapplied. Moreover, isoproterenol depolarized the membrane potential recorded using the perforated-patch method, and this depolarization was abolished by cesium ions. Thus, in mPFC pyramidal neurons, stimulation of β-adrenergic receptors up-regulates the fast-inactivating voltage-gated Na(+) currents evoked by suprathreshold depolarizations.

  2. Action-outcome relationships are represented differently by medial prefrontal and orbitofrontal cortex neurons during action execution

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    Wood, Jesse; Moghaddam, Bita

    2015-01-01

    Internal representations of action-outcome relationships are necessary for flexible adaptation of motivated behavior in dynamic environments. Prefrontal cortex (PFC) is implicated in flexible planning and execution of goal-directed actions, but little is known about how information about action-outcome relationships is represented across functionally distinct regions of PFC. Here, we observe distinct patterns of action-evoked single unit activity in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) during a task in which the relationship between outcomes and actions was independently manipulated. The mPFC encoded changes in the number of actions required to earn a reward, but not fluctuations in outcome magnitude. In contrast, OFC neurons decreased firing rates as outcome magnitude was increased, but were insensitive to changes in action requirement. A subset of OFC neurons also tracked outcome availability. Pre-outcome anticipatory activity in both mPFC and OFC was altered when reward expectation was reduced, but did not differ with outcome magnitude. These data provide novel evidence that PFC regions encode distinct information about the relationship between actions and impending outcomes during action execution. PMID:26467523

  3. Mapping the functional network of medial prefrontal cortex by combining optogenetics and fMRI in awake rats.

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    Liang, Zhifeng; Watson, Glenn D R; Alloway, Kevin D; Lee, Gangchea; Neuberger, Thomas; Zhang, Nanyin

    2015-08-15

    The medial prefrontal cortex (mPFC) plays a critical role in multiple cognitive and limbic functions. Given its vital importance, investigating the function of individual mPFC circuits in animal models has provided critical insight into the neural basis underlying different behaviors and psychiatric conditions. However, our knowledge regarding the mPFC whole-brain network stays largely at the anatomical level, while the functional network of mPFC, which can be dynamic in different conditions or following manipulations, remains elusive especially in awake rodents. Here we combined optogenetic stimulation and functional magnetic resonance imaging (opto-fMRI) to reveal the network of brain regions functionally activated by mPFC outputs in awake rodents. Our data showed significant increases in blood-oxygenation-level dependent (BOLD) signals in prefrontal, striatal and limbic regions when mPFC was optically stimulated. This activation pattern was robust, reproducible, and did not depend on the stimulation period in awake rats. BOLD signals, however, were substantially reduced when animals were anesthetized. In addition, regional brain activation showing increased BOLD signals during mPFC stimulation was corroborated by electrophysiological recordings. These results expand the applicability of the opto-fMRI approach from sensorimotor processing to cognition-related networks in awake rodents. Importantly, it may help elucidate the circuit mechanisms underlying numerous mPFC-related functions and behaviors that need to be assessed in the awake state.

  4. Characterization of electrically evoked field potentials in the medial prefrontal cortex and orbitofrontal cortex of the rat: modulation by monoamines.

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    Wallace, Joanne; Jackson, Rosanna K; Shotton, Tanya L; Munjal, Ishaana; McQuade, Richard; Gartside, Sarah E

    2014-02-01

    Medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) play critical roles in cognition and behavioural control. Glutamatergic, GABAergic, and monoaminergic dysfunction in the prefrontal cortex has been hypothesised to underlie symptoms in neuropsychiatric disorders. Here we characterised electrically-evoked field potentials in the mPFC and OFC. Electrical stimulation evoked field potentials in layer V/VI of the mPFC and layer V of the OFC. The earliest component (approximately 2 ms latency) was insensitive to glutamate receptor blockade and was presumed to be presynaptic. Later components were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX (20 µM)) and were assumed to reflect monosynaptic (latency 4-6 ms) and polysynaptic activity (latency 6-40 ms) mediated by glutamate via AMPA/kainate receptor. In the mPFC, but not the OFC, the monosynaptic component was also partly blocked by 2-amino-5-phosphonopentanoic acid (AP-5 (50-100µM)) indicating the involvement of NMDA receptors. Bicuculline (3-10 µM) enhanced the monosynaptic component suggesting electrically-evoked and/or glutamate induced GABA release inhibits the monosynaptic component via GABAA receptor activation. There were complex effects of bicuculline on polysynaptic components. In the mPFC both the mono- and polysynaptic components were attenuated by 5-HT (10-100 µM) and NA (30 and 60 µM) and the monosynaptic component was attenuated by DA (100 µM). In the OFC the mono- and polysynaptic components were also attenuated by 5-HT (100 µM), NA (10-100 µM) but DA (10-100 µM) had no effect. We propose that these pharmacologically characterised electrically-evoked field potentials in the mPFC and OFC are useful models for the study of prefrontal cortical physiology and pathophysiology.

  5. Different forms of decision-making involve changes in the synaptic strength of the thalamic, hippocampal, and amygdalar afferents to the medial prefrontal cortex

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    Juan Carlos López-Ramos

    2015-01-01

    Full Text Available Decision-making and other cognitive processes are assumed to take place in the prefrontal cortex. In particular, the medial prefrontal cortex is identified in rodents by its dense connectivity with the mediodorsal thalamus, and because of its inputs from other sites, such as hippocampus and amygdala. The aim of this study was to find a putative relationship between the behavior of mice during the performance of decision-making tasks that involve penalties as a consequence of induced actions, and the strength of field postsynaptic potentials evoked in the prefrontal cortex from its thalamic, hippocampal, and amygdalar afferents. Mice were chronically implanted with stimulating electrodes in the mediodorsal thalamus, the hippocampal CA1 area, or the basolateral amygdala, and with recording electrodes in the prelimbic/infralimbic area of the prefrontal cortex. Additional stimulating electrodes aimed at evoking negative reinforcements were implanted on the trigeminal nerve. Field postsynaptic potentials evoked at the medial prefrontal cortex from the three selected projecting areas during the food/shock decision-making task decreased in amplitude with shock intensity and animals’ avoidance of the reward. Field postsynaptic potentials collected during the operant task also decreased in amplitude (but that evoked by amygdalar stimulation when lever presses were associated with a trigeminal shock. Results showed a general decrease in the strength of these potentials when animals inhibited their natural or learned appetitive behaviors, suggesting an inhibition of the prefrontal cortex in these conflicting situations.

  6. Cellular resolution optical access to brain regions in fissures: imaging medial prefrontal cortex and grid cells in entorhinal cortex.

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    Low, Ryan J; Gu, Yi; Tank, David W

    2014-12-30

    In vivo two-photon microscopy provides the foundation for an array of powerful techniques for optically measuring and perturbing neural circuits. However, challenging tissue properties and geometry have prevented high-resolution optical access to regions situated within deep fissures. These regions include the medial prefrontal and medial entorhinal cortex (mPFC and MEC), which are of broad scientific and clinical interest. Here, we present a method for in vivo, subcellular resolution optical access to the mPFC and MEC using microprisms inserted into the fissures. We chronically imaged the mPFC and MEC in mice running on a spherical treadmill, using two-photon laser-scanning microscopy and genetically encoded calcium indicators to measure network activity. In the MEC, we imaged grid cells, a widely studied cell type essential to memory and spatial information processing. These cells exhibited spatially modulated activity during navigation in a virtual reality environment. This method should be extendable to other brain regions situated within deep fissures, and opens up these regions for study at cellular resolution in behaving animals using a rapidly expanding palette of optical tools for perturbing and measuring network structure and function.

  7. Preserved self-awareness following extensive bilateral brain damage to the insula, anterior cingulate, and medial prefrontal cortices.

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    Carissa L Philippi

    Full Text Available It has been proposed that self-awareness (SA, a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC, and the medial prefrontal cortex (mPFC. Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his "autobiographical self", the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices.

  8. Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices

    Science.gov (United States)

    Khalsa, Sahib S.; Damasio, Antonio; Tranel, Daniel; Landini, Gregory; Williford, Kenneth

    2012-01-01

    It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his “autobiographical self”, the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices. PMID:22927899

  9. Neural structures underlying set-shifting: roles of medial prefrontal cortex and anterior cingulate cortex.

    Science.gov (United States)

    Bissonette, Gregory B; Powell, Elizabeth M; Roesch, Matthew R

    2013-08-01

    Impaired attentional set-shifting and inflexible decision-making are problems frequently observed during normal aging and in several psychiatric disorders. To understand the neuropathophysiology of underlying inflexible behavior, animal models of attentional set-shifting have been developed to mimic tasks such as the Wisconsin Card Sorting Task (WCST), which tap into a number of cognitive functions including stimulus-response encoding, working memory, attention, error detection, and conflict resolution. Here, we review many of these tasks in several different species and speculate on how prefrontal cortex and anterior cingulate cortex might contribute to normal performance during set-shifting. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala.

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    Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

    2011-09-01

    Neural correlates involved in the formation of negative impression from face were investigated using event-related functional magnetic resonance imaging and a partial conditioning paradigm. Eighteen normal volunteers underwent imaging while they viewed the faces of two unfamiliar individuals: one individual's face was partially accompanied by negative emotion but the other's was not. After the volunteers learned the relationship between the faces and the emotion, they formed a more negative impression of the person's face when the emotion was presented. Subtraction analysis of the individuals' neutral faces revealed activation in the dorsal anterior cingulate cortex and superior temporal sulcus, but this activity did not correlate with the change of impression from face. On the other hand, the response in the left amygdala negatively correlated with the change of impression from face in the first run. Time modulation analysis revealed that activity in the dorsomedial prefrontal cortex associated with negative emotion was the largest in the initial part of the acquisition. These results suggest that a negative impression from face may be formed by orchestrated activity in the dorsomedial prefrontal cortex, dorsal anterior cingulate cortex and amygdala, and that the activity has a prominent role in the initial acquisition of negative emotion.

  11. Age differences in medial prefrontal activity for subsequent memory of truth value

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    Cassidy, Brittany S.; Hedden, Trey; Yoon, Carolyn; Gutchess, Angela H.

    2014-01-01

    Much research has demonstrated that aging is marked by decreased source memory relative to young adults, yet a smaller body of work has demonstrated that increasing the socioemotional content of source information may be one way to reduce age-related performance differences. Although dorsomedial prefrontal cortex (dmPFC) activity may support source memory among young and older adults, the extent to which one activates dorsal vs. ventral mPFC may reflect one's personal connection with incoming information. Because truth value may be one salient marker that impacts one's connection with information and allocation of attention toward incoming material, we investigated whether the perceived truth value of information differently impacts differences in mPFC activity associated with encoding source information, particularly with age. Twelve young (18–23 years) and 12 older adults (63–80 years) encoded true and false statements. Behavioral results showed similar memory performance between the age groups. With respect to neural activity associated with subsequent memory, young adults, relative to older adults, exhibited greater activity in dmPFC while older adults displayed enhanced ventromedial prefrontal cortex (vmPFC) and insula engagement relative to young. These results may potentially indicate that young adults focus on a general knowledge acquisition goal, while older adults focus on emotionally relevant aspects of the material. The findings demonstrate that age-related differences in recruitment of mPFC associated with encoding source information may in some circumstances underlie age-equivalent behavioral performance. PMID:24570672

  12. Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources.

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    Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

    2014-05-01

    Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts--for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts.

  13. Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study.

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    Bodén, R; Persson, J; Wall, A; Lubberink, M; Ekselius, L; Larsson, E-M; Antoni, G

    2017-03-07

    The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BPND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BPND) of [(11)C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BPND of [(11)C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BPND for [(11)C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.

  14. Is the subcallosal medial prefrontal cortex a common site of atrophy in Alzheimer’s disease and frontotemporal lobar degeneration?

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    Olof eLindberg

    2012-11-01

    Full Text Available Regions affected late in neurodegenerative disease are thought to be anatomically connected to regions affected earlier. The subcallosal medial prefrontal cortex (SMPC has connections with the dorsolateral prefrontal cortex (DLPFC, orbitofrontal cortex (OFC and hippocampus (HC, which are regions that may become atrophic in frontotemporal lobar degeneration (FTLD and Alzheimer’s disease (AD. We hypothesized that the SMPC is a common site of frontal atrophy in the FTLD subtypes and in AD. The volume of the SMPC, DLPFC, OFC, HC and entorhinal cortex were manually delineated for 12 subjects with frontotemporal dementia (FTD, 13 with semantic dementia (SD, 9 with progressive nonfluent aphasia (PNFA, 10 AD cases and 13 controls. Results revealed significant volume loss in the left SMPC in FTD, SD and PNFA, while the right SMPC was also atrophied in SD and FTD. In AD a non significant tendency of volume loss in the left SMPC was found (p=0.08, with no volume loss on the right side. Results indicated that volume loss reflected the degree of brain connectivity. In SD and AD temporal regions displayed most atrophy. Among the frontal regions, the SMPC (which receives the strongest temporal projections demonstrated most volume loss, the OFC (which receives less temporal projections less volume loss, while the DLPFC (which is at multisynaptic distance from the temporal regions demonstrated no volume loss. In PNFA, the left SMPC was atrophic, possibly reflecting progression from the left anterior insula, while FTD patients may have had SMPC atrophy at the initial stages of the disease. Atrophy of the SMPC may thus be affected by either initial temporal or initial frontal atrophy, making it a common site of frontal atrophy in the dementia subtypes investigated.

  15. Anisomycin in the medial prefrontal cortex reduces reconsolidation of cocaine-associated memories in the rat self-administration model.

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    Sorg, Barbara A; Todd, Ryan P; Slaker, Megan; Churchill, Lynn

    2015-05-01

    We tested the hypothesis that infusion of anisomycin into the medial prefrontal cortex (mPFC) disrupts the reconsolidation of a cocaine-associated memory in the rat cocaine self-administration model. Male Sprague-Dawley rats were trained to lever press for cocaine self-administration (0.5 mg/kg/infusion) along with a cue light presentation on an FR1 followed by an FR3 schedule of reinforcement for 2 h/day. Rats were then given extinction sessions or an equivalent forced abstinence period followed by a 5 min memory reactivation session during which time they received an ip cocaine injection (10 mg/kg, ip) and were allowed to press for contingent cue light presentation. Immediately after reactivation, they were administered an intra-mPFC infusion of vehicle or anisomycin. Two additional control groups received extinction and either no memory reactivation and intra-mPFC infusions as above or intra-mPFC infusions 6 h after memory reactivation. A fourth group received forced abstinence and intra-mPFC infusions immediately after memory reactivation. Combined cocaine + cue-induced reinstatement was given 2-3 days (early) and 8-12 days (late) later. Rats given anisomycin in the Extinction + Reactivation demonstrated decreased reinstatement, while anisomycin treatment did not alter behavior in any of the other three groups. These results suggest that extinction training may recruit the mPFC such that it renders the memory susceptible to disruption by anisomycin. These findings have implications for using extinction training prior to or in conjunction with other therapies, including reconsolidation disruption, to enhance prefrontal control over drug-seeking behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Broadband neurophysiological abnormalities in the medial prefrontal region of the default-mode network in adults with ADHD.

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    Wilson, Tony W; Franzen, John D; Heinrichs-Graham, Elizabeth; White, Matthew L; Knott, Nichole L; Wetzel, Martin W

    2013-03-01

    Previous investigations of the default-mode network (DMN) in persons with attention-deficit/hyperactivity disorder (ADHD) have shown reduced functional connectivity between the anterior and posterior aspects. This finding was originally demonstrated in adults with ADHD, then in youth with ADHD, and has been tentatively linked to ultra low frequency oscillations within the DMN. The current study evaluates the specificity of DMN abnormalities to neuronal oscillations in the ultra low frequency range, and examines the regional specificity of these DMN aberrations in medicated and unmedicated adults with, and those without ADHD. An individually matched sample of adults with and without ADHD completed 6-minute sessions of resting-state magnetoencephalography (MEG). Participants with ADHD were known responders to stimulant medications and completed two sessions (predrug/postdrug). MEG data were coregistered to the participant's MRI, corrected for head motion, fitted to a regional-level source model, and subjected to spectral analyses to extract neuronal population activity in regions of the DMN. The unmedicated adults with ADHD exhibited broadband deficits in medial prefrontal cortices (MPFC), but not other DMN regions compared to adults without ADHD. Unmedicated patients also showed abnormal cross-frequency coupling in the gamma range between the MPFC and posterior cingulate areas, and disturbed balance within the DMN as activity in posterior regions was stronger than frontal regions at beta and lower frequencies, which dissipated at higher γ-frequencies. Administration of pharmacotherapy significantly increased prefrontal alpha activity (8-14 Hz) in adults with ADHD, and decreased the cross-frequency gamma coupling. These results indicate that neurophysiological aberrations in the DMN of patients with ADHD are not limited to ultra slow oscillations, and that they may be primarily attributable to abnormal broadband activity in the MPFC.

  17. Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype.

    Science.gov (United States)

    Eisinger, Brian E; Driessen, Terri M; Zhao, Changjiu; Gammie, Stephen C

    2014-01-01

    The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for post-partum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for post-partum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Post-partum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum (LS) and medial preoptic area (MPOA), enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for post-partum psychosis with aspects of schizophrenia

  18. Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype

    Directory of Open Access Journals (Sweden)

    Brian E Eisinger

    2014-04-01

    Full Text Available The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for postpartum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for postpartum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC, a region implicated in both maternal behavior and psychiatric disorders. Postpartum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET, we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets and bipolar disorder (BPD, 3 of 3 sets. In contrast to previous studies of maternal lateral septum and medial preoptic area, enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets. Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7, glutamate metabotropic receptor 3 (Grm3, platelet derived growth factor, beta polypeptide (Pdgfrb, and nuclear receptor subfamily 1, group D, member 1 (Nr1d1. RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1 and proenkephalin (Penk. Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for postpartum psychosis with aspects of schizophrenia and BPD.

  19. Association of medial prefrontal cortex connectivity with consciousness level and its outcome in patients with acquired brain injury.

    Science.gov (United States)

    Liu, Xiaoyan; Li, Jingqi; Gao, Jian; Zhou, Zhen; Meng, Fanxia; Pan, Gang; Luo, Benyan

    2017-08-01

    Medial prefrontal cortex (mPFC) is usually known for participating in virtually all self related processing. However, few have investigated the role of mPFC in modulating conscious awareness. This study aimed to depict the relationship between the mPFC connectivity and the severity and outcome of the disorders of consciousness (DOC) among patients with acquired brain injury. Thirty-four patients with DOC (17 in a minimally conscious state and 17 in an unresponsive wakefulness syndrome/vegetative state) and 11 healthy controls were recruited, underwent clinical assessment and resting-state functional MRI scan, and were further followed up to evaluate recovery outcome using the Glasgow Outcome Scale. The mPFC connectivity was then analyzed, by comparing DOC patients to healthy controls at baseline, and by comparing "recovered consciousness" and "non-recovered consciousness" patients at follow-up, as identified by graph theory. As a result, enhanced mPFC connectivity against weakened posteromedial cortex connectivity was observed in a minimally conscious state, not in an unresponsive wakefulness syndrome/vegetative state. Besides, increased mPFC connectivity was significantly associated with consciousness recovery. In conclusion, the mPFC connectivity could possibly serve as a mark to track the severity and outcome of DOC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Self-distancing improves interpersonal perceptions and behavior by decreasing medial prefrontal cortex activity during the provision of criticism.

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    Leitner, Jordan B; Ayduk, Ozlem; Mendoza-Denton, Rodolfo; Magerman, Adam; Amey, Rachel; Kross, Ethan; Forbes, Chad E

    2016-12-20

    Previous research suggests that people show increased self-referential processing when they provide criticism to others, and that this self-referential processing can have negative effects on interpersonal perceptions and behavior. The current research hypothesized that adopting a self-distanced perspective (i.e. thinking about a situation from a non-first person point of view), as compared with a typical self-immersed perspective (i.e. thinking about a situation from a first-person point of view), would reduce self-referential processing during the provision of criticism, and in turn improve interpersonal perceptions and behavior. We tested this hypothesis in an interracial context since research suggests that self-referential processing plays a role in damaging interracial relations. White participants prepared for mentorship from a self-immersed or self-distanced perspective. They then conveyed negative and positive evaluations to a Black mentee while electroencephalogram (EEG) was recorded. Source analysis revealed that priming a self-distanced (vs self-immersed) perspective predicted decreased activity in regions linked to self-referential processing (medial prefrontal cortex; MPFC) when providing negative evaluations. This decreased MPFC activity during negative evaluations, in turn, predicted verbal feedback that was perceived to be more positive, warm and helpful. Results suggest that self-distancing can improve interpersonal perceptions and behavior by decreasing self-referential processing during the provision of criticism.

  1. Neurobiological foundations of multisensory processing integration in people with autism spectrum disorders: The role of the medial prefrontal cortex

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    Sonia eMartínez-Sanchis

    2014-12-01

    Full Text Available This review aims to relate the sensory processing problems in people with Autism spectrum disorders (ASD, especially Multisensory interaction (MSI, to the role of the medial prefrontal cortex (mPFC by exploring neuroanatomical findings; brain connectivity and Default Network (DN; global or locally directed attention; and temporal multisensory binding. The mPFC is part of the brain’s DN, which is deactivated when attention is focused on a particular task and activated on rest when spontaneous cognition emerges. In those with ASD, it is hypoactive and the higher the social impairment the greater the atypical activity. With an immature DN, cross-modal integration is impaired, resulting in a collection of disconnected fragments instead of a coherent global perception. The deficit in MSI may lie in the temporal synchronization of neural networks. The time interval in which the stimulation of one sensory channel could influence another would be higher, preventing integration in the typical shorter time range. Thus, the underconnectivity between distant brain areas would be involved in top-down information processes (relying on global integration of data from different sources and would enhance low level perception processes such as over focused attention to sensory details.

  2. Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period.

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    Sabihi, Sara; Dong, Shirley M; Durosko, Nicole E; Leuner, Benedetta

    2014-01-01

    The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, but not virgin, females. In addition, OTR blockade in the postpartum mPFC impaired maternal care behaviors and enhanced maternal aggression. Overall, these results suggest that OT in the mPFC modulates maternal care and aggression, as well as anxiety-like behavior, during the postpartum period. Although the relationship among these behaviors is complicated and further investigation is required to refine our understanding of OT actions in the maternal mPFC, these data nonetheless provide new insights into neural circuitry of OT-mediated postpartum behaviors.

  3. Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex.

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    Littlefield, Melissa M; Dietz, Martin J; Fitzgerald, Des; Knudsen, Kasper J; Tonks, James

    2015-01-01

    "Truth" has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning.

  4. Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

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    Chun-Lei Zhang

    Full Text Available Methylphenidate (MPH, commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD. Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC. To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+ increase, but does not require PKA and extracellular Ca(2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

  5. Prenatal alcohol exposure modifies glucocorticoid receptor subcellular distribution in the medial prefrontal cortex and impairs frontal cortex-dependent learning.

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    Andrea M Allan

    Full Text Available Prenatal alcohol exposure (PAE has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD. Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice.

  6. Medial prefrontal and anterior cingulate cortical thickness predicts shared individual differences in self-generated thought and temporal discounting.

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    Bernhardt, Boris C; Smallwood, Jonathan; Tusche, Anita; Ruby, Florence J M; Engen, Haakon G; Steinbeis, Nikolaus; Singer, Tania

    2014-04-15

    When deprived of compelling perceptual input, the mind is often occupied with thoughts unrelated to the immediate environment. Previous behavioral research has shown that this self-generated task-unrelated thought (TUT), especially under non-demanding conditions, relates to cognitive capacities such as creativity, planning, and reduced temporal discounting. Despite the frequency and importance of this type of cognition, little is known about its structural brain basis. Using MRI-based cortical thickness measures in 37 participants, we were able to show that individuals with a higher tendency to engage in TUT under low-demanding conditions (but not under high-demanding conditions) show an increased thickness of medial prefrontal cortex (mPFC) and anterior/midcingulate cortex. Thickness of these regions also related to less temporal discounting (TD) of monetary rewards in an economic task, indicative of more patient decision-making. The findings of a shared structural substrate in mPFC and anterior/midcingulate cortex underlying both TUT and TD suggest an important role of these brain regions in supporting the self-generation of information that is unrelated to the immediate environment and which may be adaptive in nature. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. The temporal structure of resting-state brain activity in the medial prefrontal cortex predicts self-consciousness.

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    Huang, Zirui; Obara, Natsuho; Davis, Henry Hap; Pokorny, Johanna; Northoff, Georg

    2016-02-01

    Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity.

  8. Effects of lamotrigine on PCP-evoked elevations in monoamine levels in the medial prefrontal cortex of freely moving rats.

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    Quarta, Davide; Large, Charles H

    2011-12-01

    Lamotrigine is suggested to have potential as an add-on treatment for patients with schizophrenia. Supporting evidence comes from the efficacy of the drug in models of psychotic-like behaviour induced by N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP). These drugs enhance levels of the monoamines in the cortex, which may contribute to their psychotomimetic effects. The ability of lamotrigine to prevent these neurochemical changes has not been examined. We studied PCP-evoked overflow of noradrenaline, dopamine and serotonin in the medial prefrontal cortex of awake rats using microdialysis. Rats were administered lamotrigine or vehicle, followed by PCP. Locomotor activity was also recorded before and after drug treatment. Lamotrigine did not have an influence on basal levels of the monoamines, but significantly reduced PCP-evoked overflow of dopamine and serotonin; PCP-evoked overflow of noradrenaline was also reduced by lamotrigine, but not to a significant degree. In contrast, PCP-induced hyperactivity was unaffected by lamotrigine. It is concluded that lamotrigine can modify PCP-evoked monoamine overflow in the cortex, consistent with an ability to prevent the psychotomimetic effects of NMDA receptor antagonists in rodents and humans. The dissociation between monoamine overflow and locomotor activity suggests the involvement of different brain circuits; relevance to the treatment of schizophrenia is also discussed.

  9. Hyperconnectivity and slow synapses during early development of medial prefrontal cortex in a mouse model for mental retardation and autism.

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    Testa-Silva, Guilherme; Loebel, Alex; Giugliano, Michele; de Kock, Christiaan P J; Mansvelder, Huibert D; Meredith, Rhiannon M

    2012-06-01

    Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex (mPFC) networks in the Fmr1-KO mouse model for mental retardation and autism. In line with predictions from neurocognitive theory, we found that neighboring pyramidal neurons were hyperconnected during a critical period in early mPFC development. Surprisingly, excitatory synaptic connections between Fmr1-KO pyramidal neurons were significantly slower and failed to recover from short-term depression as quickly as wild type (WT) synapses. By 4-5 weeks of mPFC development, connectivity rates were identical for both KO and WT pyramidal neurons and synapse dynamics changed from depressing to facilitating responses with similar properties in both groups. We propose that the early alteration in connectivity and synaptic recovery are tightly linked: using a network model, we show that slower synapses are essential to counterbalance hyperconnectivity in order to maintain a dynamic range of excitatory activity. However, the slow synaptic time constants induce decreased responsiveness to low-frequency stimulation, which may explain deficits in integration and early information processing in attentional neuronal networks in NDDs.

  10. The infralimbic and prelimbic medial prefrontal cortices have differential functions in the expression of anxiety-like behaviors in mice.

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    Suzuki, Satoshi; Saitoh, Akiyoshi; Ohashi, Masanori; Yamada, Misa; Oka, Jun-Ichiro; Yamada, Mitsuhiko

    2016-05-01

    The medial prefrontal cortex is a heterogeneous cortical structure composed of several nuclei, including the prelimbic (PL) and infralimbic (IL) cortices. We previously demonstrated in mice that PL activation with the sodium channel activator veratrine induces anxiety-like behaviors. However, the role of IL in the regulation of anxiety-like behaviors remained unclear. Therefore, in the present study, we investigated the role of the IL in the regulation of anxiety-like behaviors using pharmacological activation model with veratrine, and compared it with the role of the PL. Extracellular glutamate levels were measured by in vivo microdialysis-HPLC with an electrochemical detector, and behaviors were assessed using the open field test. In this study, extracellular glutamate levels rose significantly after perfusion of veratrine in the IL and PL. Interestingly, the PL activation produced anxiety-like behaviors, whereas the activation of the IL produced no anxiety-like behavior in mice. Although the IL is adjacent to the PL, these two regions of the brain have differential functions in the expression of anxiety-like behaviors.

  11. Serotonin 2a Receptor and Serotonin 1a Receptor Interact Within the Medial Prefrontal Cortex During Recognition Memory in Mice

    Science.gov (United States)

    Morici, Juan F.; Ciccia, Lucia; Malleret, Gaël; Gingrich, Jay A.; Bekinschtein, Pedro; Weisstaub, Noelia V.

    2015-01-01

    Episodic memory, can be defined as the memory for unique events. The serotonergic system one of the main neuromodulatory systems in the brain appears to play a role in it. The serotonin 2a receptor (5-HT2aR) one of the principal post-synaptic receptors for 5-HT in the brain, is involved in neuropsychiatric and neurological disorders associated with memory deficits. Recognition memory can be defined as the ability to recognize if a particular event or item was previously encountered and is thus considered, under certain conditions, a form of episodic memory. As human data suggest that a constitutively decrease of 5-HT2A signaling might affect episodic memory performance we decided to compare the performance of mice with disrupted 5-HT2aR signaling (htr2a−/−) with wild type (htr2a+/+) littermates in different recognition memory and working memory tasks that differed in the level of proactive interference. We found that ablation of 5-HT2aR signaling throughout development produces a deficit in tasks that cannot be solved by single item strategy suggesting that 5-HT2aR signaling is involved in interference resolution. We also found that in the absence of 5-HT2aR signaling serotonin has a deleterious effect on recognition memory retrieval through the activation of 5-HT1aR in the medial prefrontal cortex. PMID:26779016

  12. Imipramine-induced c-Fos expression in the medial prefrontal cortex is decreased in the ACTH-treated rats.

    Science.gov (United States)

    Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Gomita, Yutaka; Araki, Hiroaki; Cui, Ranji

    2013-11-01

    Previous studies have shown that the antidepressive-like effect of tricyclic antidepressants is blocked by repeated treatments with adrenocorticotropic hormone (ACTH). However, little is known about the neuroanatomy underlying the mechanism of the imipramine treatment-resistant depression model. In the present study, first experimental evidence showed no significant difference of the serum imipramine concentrations between the saline and ACTH-treated rats. In further study, imipramine produced significant increases in the c-Fos expression in the medial prefrontal cortex (mPFC), the dentate gyrus of the hippocampus (DGH), and the central nucleus of the amygdala (CeA), in rats repeatedly treated with saline. The imipramine-increased c-Fos immunoreactivity was suppressed in the mPFC of rats repeatedly treated with ACTH. However, there was no significant difference in c-Fos expression in the DGH and CeA between ACTH- and saline-treated rats. These results suggest that the mPFC is maybe involved in effects of the imipramine in the ACTH-treated rats.

  13. Serotonin 2a Receptor and serotonin 1a receptor interact within the medial prefrontal cortex during recognition memory in mice

    Directory of Open Access Journals (Sweden)

    Juan Facundo Morici

    2015-12-01

    Full Text Available Episodic memory, can be defined as the memory for unique events. The serotonergic system one of the main neuromodulatory systems in the brain appears to play a role in it. The serotonin 2a receptor (5-HT2aR one of the principal post-synaptic receptors for 5-HT in the brain, is involved in neuropsychiatric and neurological disorders associated with memory deficits. Recognition memory can be defined as the ability to recognize if a particular event or item was previously encountered and is thus considered, under certain conditions, a form of episodic memory. As human data suggest that a constitutively decrease of 5-HT2A signaling might affect episodic memory performance we decided to compare the performance of mice with disrupted 5-HT2aR signaling (htr2a -/- with wild type (htr2a+/+ littermates in different recognition memory and working memory tasks that differed in the level of proactive interference. We found that ablation of 5-HT2aR signaling throughout development produces a deficit in tasks that cannot be solved by single item strategy suggesting that 5-HT2aR signaling is involved in interference resolution. We also found that in the absence of 5-HT2aR signaling serotonin has a deleterious effect on recognition memory retrieval through the activation of 5-HT1aR in the medial prefrontal cortex.

  14. Gender differences in cognitive Theory of Mind revealed by transcranial direct current stimulation on medial prefrontal cortex

    Science.gov (United States)

    Adenzato, Mauro; Brambilla, Michela; Manenti, Rosa; De Lucia, Lucia; Trojano, Luigi; Garofalo, Sara; Enrici, Ivan; Cotelli, Maria

    2017-01-01

    Gender differences in social cognition are a long discussed issue, in particular those concerning Theory of Mind (ToM), i.e., the ability to explain and predict other people’s mental states. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal tDCS over the medial prefrontal cortex (mPFC) selectively enhances cognitive ToM performance in females. In the first experiment we administered to sixteen females and sixteen males a cognitive ToM task during anodal or placebo tDCS over the mPFC. In the second experiment further sixteen females completed the task receiving anodal or placebo tDCS over the vertex. The results showed that anodal tDCS over the mPFC enhances ToM in females but not in males, an effect indicated by enhanced ToM in females that received anodal tDCS over the mPFC compared with females that received tDCS over the vertex. These findings are relevant for three reasons. First, we found evidence of gender-related differences in cognitive ToM, extending previous findings concerning affective ToM. Second, these differences emerge with anodal stimulation of the mPFC, confirming the crucial role of this area in cognitive ToM. Third, we show that taking into account gender-related differences is mandatory for the investigation of ToM. PMID:28117378

  15. Self-esteem modulates dorsal medial prefrontal cortical response to self-positivity bias in implicit self-relevant processing.

    Science.gov (United States)

    Yang, Juan; Dedovic, Katarina; Guan, Lili; Chen, Yu; Qi, Mingming

    2014-11-01

    Processing self-related material recruits similar neural networks regardless of whether the self-relevance is made explicit or not. However, when considering the neural mechanisms that distinctly underlie cognitive and affective components of self-reflection, it is still unclear whether the same mechanisms are involved when self-reflection is explicit or implicit, and how these mechanisms may be modulated by individual personality traits, such as self-esteem. In the present functional MRI study, 25 participants were exposed to positive and negative words that varied with respect to the degree of self-relevance for each participant; however, the participants were asked to make a judgment about the color of the words. Regions-of-interest analysis showed that medial prefrontal cortex (mPFC) and posterior cingulate cortex were associated with gauging the self-relevance of information. However, no main effect of valence or an interaction effect between self-relevance and valence was observed. Further, positive correlations were observed between levels of self-esteem and response within dorsal mPFC (dmPFC) both in the contrast positive-high in self-relevance trials vs positive-low in self-relevance trials and in the contrast negative-low in self-relevance trials vs positive-low in self-relevance trials. These results suggested that the activation of dmPFC may be particularly associated with the processes of self-positivity bias.

  16. Glutamate concentration in the medial prefrontal cortex predicts resting-state cortical-subcortical functional connectivity in humans.

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    Niall W Duncan

    Full Text Available Communication between cortical and subcortical regions is integral to a wide range of psychological processes and has been implicated in a number of psychiatric conditions. Studies in animals have provided insight into the biochemical and connectivity processes underlying such communication. However, to date no experiments that link these factors in humans in vivo have been carried out. To investigate the role of glutamate in individual differences in communication between the cortex--specifically the medial prefrontal cortex (mPFC--and subcortical regions in humans, a combination of resting-state fMRI, DTI and MRS was performed. The subcortical target regions were the nucleus accumbens (NAc, dorsomedial thalamus (DMT, and periaqueductal grey (PAG. It was found that functional connectivity between the mPFC and each of the NAc and DMT was positively correlated with mPFC glutamate concentrations, whilst functional connectivity between the mPFC and PAG was negatively correlated with glutamate concentration. The correlations involving mPFC glutamate and FC between the mPFC and each of the DMT and PAG were mirrored by correlations with structural connectivity, providing evidence that the glutamatergic relationship may, in part, be due to direct connectivity. These results are in agreement with existing results from animal studies and may have relevance for MDD and schizophrenia.

  17. Theta synchronization between medial prefrontal cortex and cerebellum is associated with adaptive performance of associative learning behavior.

    Science.gov (United States)

    Chen, Hao; Wang, Yi-jie; Yang, Li; Sui, Jian-feng; Hu, Zhi-an; Hu, Bo

    2016-02-16

    Associative learning is thought to require coordinated activities among distributed brain regions. For example, to direct behavior appropriately, the medial prefrontal cortex (mPFC) must encode and maintain sensory information and then interact with the cerebellum during trace eyeblink conditioning (TEBC), a commonly-used associative learning model. However, the mechanisms by which these two distant areas interact remain elusive. By simultaneously recording local field potential (LFP) signals from the mPFC and the cerebellum in guinea pigs undergoing TEBC, we found that theta-frequency (5.0-12.0 Hz) oscillations in the mPFC and the cerebellum became strongly synchronized following presentation of auditory conditioned stimulus. Intriguingly, the conditioned eyeblink response (CR) with adaptive timing occurred preferentially in the trials where mPFC-cerebellum theta coherence was stronger. Moreover, both the mPFC-cerebellum theta coherence and the adaptive CR performance were impaired after the disruption of endogenous orexins in the cerebellum. Finally, association of the mPFC -cerebellum theta coherence with adaptive CR performance was time-limited occurring in the early stage of associative learning. These findings suggest that the mPFC and the cerebellum may act together to contribute to the adaptive performance of associative learning behavior by means of theta synchronization.

  18. Sertraline and curcumin prevent stress-induced morphological changes of dendrites and neurons in the medial prefrontal cortex of rats.

    Science.gov (United States)

    Noorafshan, A; Abdollahifar, M-A; Karbalay-Doust, S; Asadi-Golshan, R; Rashidian-Rashidabadi, A

    2015-01-01

    Stress induces structural and behavioral impairments. The changes in dendrites and neurons are accompanied by impairments in the tasks mediated by the medial prefrontal cortex (mPFC). The present study was conducted to evaluate the structural changes of the dendrites and neurons of the mPFC after stress using stereological methods. In addition, the effects of a natural and a synthetic substance, i.e., curcumin and sertraline, were evaluated. The rats were divided into 7 groups: stress + distilled water, stress + olive oil, curcumin (100 mg/kg/day), sertraline (10 mg/kg/day), stress + curcumin, stress + sertraline, and control groups. The animals were submitted to chronic variable stress for 56 days. The results showed an average 15% reduction in the length of the dendrites per neuron in the mPFC after stress (p sertraline can prevent the loss of spines and reduction of dendrite length, volume and surface area of the neurons. Sertraline and curcumin can prevent structural changes of the neurons and dendrites induced by stress in the mPFC of rats.

  19. Dorsal medial prefrontal cortex (MPFC) circuitry in rodent models of cocaine use: implications for drug addiction therapies.

    Science.gov (United States)

    Jasinska, Agnes J; Chen, Billy T; Bonci, Antonello; Stein, Elliot A

    2015-03-01

    Although the importance of the medial prefrontal cortex (MPFC) in cocaine addiction is well established, its precise contribution to cocaine seeking, taking and relapse remains incompletely understood. In particular, across two different models of cocaine self-administration, pharmacological or optogenetic activation of the dorsal MPFC has been reported to sometimes promote and sometimes inhibit cocaine seeking. We highlight important methodological differences between the two experimental paradigms and propose a framework to potentially reconcile the apparent discrepancy. We also draw parallels between these pre-clinical models of cocaine self-administration and human neuro-imaging studies in cocaine users, and argue that both lines of evidence point to dynamic interactions between cue-reactivity processes and control processes within the dorsal MPFC circuitry. From a translational perspective, these findings underscore the importance of interventions and therapeutics targeting not just a brain region, but a specific computational process within that brain region, and may have implications for the design and implementation of more effective treatments for human cocaine addiction. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  20. Oscillatory activity in the medial prefrontal cortex and nucleus accumbens correlates with impulsivity and reward outcome.

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    Nicholas A Donnelly

    Full Text Available Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC and nucleus accumbens (NAcb and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT, which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50-60 Hz LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7-9 Hz LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour.

  1. STRESS-INDUCED CHANGES IN EXTRACELLULAR DOPAMINE AND SEROTONIN IN THE MEDIAL PREFRONTAL CORTEX AND DORSAL HIPPOCAMPUS OF PRENATALLY MALNOURISHED RATS

    OpenAIRE

    Mokler, David J.; Torres, Olga I.; GALLER, JANINA R.; Morgane, Peter J.

    2007-01-01

    Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The me...

  2. Opposite effective connectivity in the posterior cingulate and medial prefrontal cortex between first-episode schizophrenic patients with suicide risk and healthy controls.

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    Huiran Zhang

    Full Text Available OBJECTIVE: The schizophrenic patients with high suicide risk are characterized by depression, better cognitive function, and prominent positive symptoms. However, the neurobiological basis of suicide attempts in schizophrenia is not clear. The suicide in schizophrenia is implicated in the defects in emotional process and decision-making, which are associated with prefrontal-cingulate circuit. In order to explore the possible neurobiological basis of suicide in schizophrenia, we investigated the correlation of prefrontal-cingulate circuit with suicide risk in schizophrenia via dynamic casual modelling. METHOD: Participants were 33 first-episode schizophrenic patients comprising of a high suicide risk group (N = 14 and a low suicide risk group (N = 19. A comparison group of healthy controls (N = 15 were matched for age, gender and education. N-back tasking functional magnetic resonance imaging data was collected. RESULTS: Compared with healthy controls group, the two patients groups showed decreased task-related suppression during 2-back task state versus baseline state in the left posterior cingulate and medial prefrontal cortex; the hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex existed in both schizophrenic patients groups, but hypo-connectivity in the opposite direction only existed in the schizophrenic patients group with high suicide risk. CONCLUSIONS: The hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex may suggest that the abnormal effective connectivity was associated with risk for schizophrenia. The hypo-connectivity in the opposite direction may represent a possible correlate of increased vulnerability to suicide attempt.

  3. Effects of age and acute ethanol on glutamatergic neurotransmission in the medial prefrontal cortex of freely moving rats using enzyme-based microelectrode amperometry.

    Science.gov (United States)

    Mishra, Devesh; Harrison, Nicholas R; Gonzales, Carolina B; Schilström, Björn; Konradsson-Geuken, Åsa

    2015-01-01

    Ethanol abuse during adolescence may significantly alter development of the prefrontal cortex which continues to undergo structural remodeling into adulthood. Glutamatergic neurotransmission plays an important role during these brain maturation processes and is modulated by ethanol. In this study, we investigated glutamate dynamics in the medial prefrontal cortex of freely moving rats, using enzyme-based microelectrode amperometry. We analyzed the effects of an intraperitoneal ethanol injection (1 g/kg) on cortical glutamate levels in adolescent and adult rats. Notably, basal glutamate levels decreased with age and these levels were found to be significantly different between postnatal day (PND) 28-38 vs PND 44-55 (pprefrontal cortex and suggest that acute ethanol injections have both inhibitory and excitatory effects in adolescent rats. These effects of ethanol on the prefrontal cortex may disturb its maturation and possibly limiting individuals´ control over addictive behaviors.

  4. The Dorsal Medial Prefrontal Cortex Is Recruited by High Construal of Non-social Stimuli

    Science.gov (United States)

    Baetens, Kris L. M. R.; Ma, Ning; Van Overwalle, Frank

    2017-01-01

    The dorsomedial prefrontal cortex (dmPFC) is part of the mentalizing network, a set of brain regions consistently engaged in inferring mental states. However, its precise function in this network remains unclear. It has recently been proposed that the dmPFC is involved in high-level abstract (i.e., categorical) identification or construction of both social and non-social stimuli, referred to as “high construal.” This was based on the observation of greater activation in the dmPFC shared by a high construal social condition (trait inference based on visually presented behavior) and a high construal non-social condition (categorization of visually presented objects) vs. matched low construal conditions (visual description of the same pictures). However, dmPFC activation has been related to task contexts requiring responses based on self-guided generation of mental content or decisions as compared to responses more directly determined by the experimental context (e.g., free vs. rule-governed choice). The previously reported dmPFC activity may reflect differences in task constraint (i.e., the extent to which the task context guided the process) confounded with the construal manipulation. Therefore, in the present study, we manipulated construal level and constraint independently, while participants underwent functional magnetic resonance imaging (fMRI). As before, participants visually described (low level construal) or categorized (high level construal) pictures of objects. Orthogonal to this, the description or categorization task had to be performed on either one object (low constraint) or on two objects simultaneously (high constraint), limiting the number of possible responses. Statistical analysis revealed common greater activation in both high construal conditions (high and low constraint) than in their low construal counterparts, replicating the influence of construal level on dmPFC activation (greater involvement in high than low construal), but no

  5. The medial prefrontal cortex and memory in humans: anatomical segmentation in mri and consequences of at risk prematurity

    OpenAIRE

    Córcoles Parada, Marta

    2016-01-01

    Una precisa caracterización anatómica del estatus del sistema nervioso central es crítica para entender su función y, en poblaciones clínicas, para valorar las causas de los posibles déficits cognitivos. Este trabajo supone un esfuerzo en esa dirección. Por un lado, pretende determinar el estado neuropsicológico de una población de niños prematuros de riesgo. El segundo objetivo consiste en la creación de una herramienta que permita identificar anatómicamente las subáreas de la corteza prefro...

  6. Retroactive interference of object-in-context long-term memory: role of dorsal hippocampus and medial prefrontal cortex.

    Science.gov (United States)

    Martínez, María Cecilia; Villar, María Eugenia; Ballarini, Fabricio; Viola, Haydée

    2014-12-01

    Retroactive interference (RI) is a type of amnesia in which a new learning experience can impair the expression of a previous one. It has been studied in several types of memories for over a century. Here, we aimed to study in the long-term memory (LTM) formation of an object-in-context task, defined as the recognition of a familiar object in a context different to that in which it was previously encountered. We trained rats with two sample trials, each taking place in a different context in association with different objects. Test sessions were performed 24 h later, to evaluate LTM for both object-context pairs using separate groups of trained rats. Furthermore, given the involvement of hippocampus (Hp) and medial prefrontal cortex (mPFC) in several recognition memories, we also analyzed the participation of these structures in the LTM formation of this task by the local infusion of muscimol. Our results show that object-in-context LTM formation is sensitive to RI by a different either familiar or novel object-context pair trial, experienced 1 h later. This interference occurs in a restricted temporal window and works on the LTM consolidation phase, leaving intact short-term memory expression. The second sample trial did not affect the object recognition part of the memory. Besides, muscimol treatment before the second sample trial blocks its object-in-context LTM and restores the first sample trial memory. We hypothesized that LTM-RI amnesia is probably caused by resources or cellular machinery competition in these brain regions when they are engaged in memory formation of the traces. In sum, when two different object-in-context memory traces are being processed, the second trace interferes with the consolidation of the first one requiring mPFC and CA1 dorsal Hp activation. © 2014 Wiley Periodicals, Inc.

  7. β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit.

    Science.gov (United States)

    Giustino, Thomas F; Seemann, Jocelyn R; Acca, Gillian M; Goode, Travis D; Fitzgerald, Paul J; Maren, Stephen

    2017-05-02

    Early psychological interventions, such as exposure therapy, rely on extinction learning to reduce the development of stress- and trauma-related disorders. However, recent research suggests that extinction often fails to reduce fear when administered soon after trauma. This immediate extinction deficit (IED) may be due to stress-induced dysregulation of neural circuits involved in extinction learning. We have shown that systemic β-adrenoceptor blockade with propranolol rescues the IED, but impairs delayed extinction. Here we sought to determine the neural locus of these effects. Rats underwent auditory fear conditioning and then received either immediate (30 min) or delayed (24 h) extinction training. We used bilateral intracranial infusions of propranolol into either the infralimbic division of the medial prefrontal cortex (mPFC) or the basolateral amygdala (BLA) to examine the effects of β-adrenoceptor blockade on immediate and delayed extinction learning. Interestingly, intra-BLA, but not intra-mPFC, propranolol rescued the IED; animals receiving intra-BLA propranolol prior to immediate extinction showed less spontaneous recovery of fear during extinction retrieval. Importantly, this was not due to impaired consolidation of the conditioning memory. In contrast, neither intra-BLA nor intra-mPFC propranolol affected delayed extinction learning. Overall, these data contribute to a growing literature suggesting dissociable roles for key nodes in the fear extinction circuit depending on the timing of extinction relative to conditioning. These data also suggest that heightened noradrenergic activity in the BLA underlies stress-induced extinction deficits. Propranolol may be a useful adjunct to behavioral therapeutic interventions in recently traumatized individuals who are at risk for developing trauma-related disorders.Neuropsychopharmacology advance online publication, 31 May 2017; doi:10.1038/npp.2017.89.

  8. Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task

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    Xilu eJiao

    2015-09-01

    Full Text Available Altered medial prefrontal cortex (mPFC and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding. The present study was designed to investigate the activity of mPFC and amygdala neurons during acquisition and extinction of lever-press avoidance in rats. In particular, neural activity was examined in the mPFC, intercalated cell clusters (ITCs, lateral (LA, basal (BA and central (CeA amygdala, at various time points during acquisition and extinction, using induction of the immediate early gene product, c-Fos. Neural activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as compared to the acquisition phase. In contrast, the CeA was the only region that was more activated during acquisition than during extinction. Our results indicate that elevated activity in the mPFC, BA, LA and ITCs, and reduced CeA activity is associated with extinction of active avoidance. Moreover, inhibitory neurons are activated differently in the mPFC and BA during early and late phase of acquisition and extinction, suggesting their dynamic involvement in the development of avoidance response. Together, these data start to identify the key brain regions important in active avoidance behavior, areas that could be associated with avoidance perseveration in anxiety disorders.

  9. Transient inactivation of the medial prefrontal cortex affects both anxiety and decision-making in male Wistar rats

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    Leonie ede Visser

    2011-09-01

    Full Text Available In both humans and rats high levels of anxiety impair decision-making in the Iowa Gambling Task (IGT in male subjects. Expression of the immediate early gene c-fos as marker of neural activity in rat studies indicated a role of the medial prefrontal cortex (prelimbic and infralimbic region; mPFC in mediating the relationship between anxiety and decision-making. To delineate this relationship further and assess the underlying neurobiology in more detail, we inactivated in the present study the mPFC in male rats using a mixture of the GABA-receptor agonists muscimol and baclofen. Rats were exposed to the elevated plus maze (EPM to measure effects on anxiety and to the rodent version of the IGT (r-IGT. Inactivation led to increased levels of anxiety on the EPM, while not affecting general activity. The effect in the r-IGT (trials 61-120 was dependent on levels of performance prior to inactivation (trial 41-60: inactivation of the mPFC hampered task-performance in rats, which already showed a preference for the advantageous option, but not in rats which were still choosing in a random manner. These data suggest that the mPFC becomes more strongly involved as rats have learned task-contingencies, i.e. choose for the best long-term option. Furthermore they suggest, along with the data of our earlier study, that both anxiety and decision-making in rats are mediated through a neural circuitry including at least the mPFC. The data are discussed in relation to recent data of rodent studies on the neural circuitry underlying decision-making.

  10. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity.

  11. Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats.

    Science.gov (United States)

    Sabihi, Sara; Durosko, Nicole E; Dong, Shirley M; Leuner, Benedetta

    2014-07-01

    The neuropeptide oxytocin (OT) is anxiolytic in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a target where OT acts to diminish anxiety. To investigate this possibility, female rats were administered OT bilaterally into the prelimbic (PL) region of the mPFC and anxiety-like behavior assessed. In addition, to determine if the effects of OT on anxiety-like behavior are sex dependent and to evaluate the specificity of OT, male and female anxiety-like behavior was tested following delivery of either OT or the closely related neuropeptide arginine vasopressin (AVP) into the PL mPFC. Finally, the importance of endogenous OT in the regulation of anxiety-like behavior was examined in male and female rats that received PL infusions of an OT receptor antagonist (OTR-A). Overall, even though males and females showed some differences in their baseline levels of anxiety-like behavior, OT in the PL region of the mPFC decreased anxiety regardless of sex. In contrast, neither AVP nor an OTR-A affected anxiety-like behavior in males or females. Together, these findings suggest that although endogenous OT in the PL region of the mPFC does not influence anxiety, the PL mPFC is a site where exogenous OT may act to attenuate anxiety-related behavior independent of sex.

  12. Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a DCC-dependent manner.

    Science.gov (United States)

    Reynolds, Lauren M; Makowski, Carolina S; Yogendran, Sandra V; Kiessling, Silke; Cermakian, Nicolas; Flores, Cecilia

    2015-03-13

    Initiation of drug use during adolescence is a strong predictor of both the incidence and severity of addiction throughout the lifetime. Intriguingly, adolescence is a period of dynamic refinement in the organization of neuronal connectivity, in particular medial prefrontal cortex (mPFC) dopamine circuitry. The guidance cue receptor, DCC (deleted in colorectal cancer), is highly expressed by dopamine neurons and orchestrates their innervation to the mPFC during adolescence. Furthermore, we have shown that amphetamine in adolescence regulates DCC expression in dopamine neurons. Drugs in adolescence may therefore induce their enduring behavioral effects via DCC-mediated disruption in mPFC dopamine development. In this study, we investigated the impact of repeated exposure to amphetamine during adolescence on both the development of mPFC dopamine connectivity and on salience attribution to drug context in adulthood. We compare these effects to those induced by adult exposure to an identical amphetamine regimen. Finally, we determine whether DCC signaling within dopamine neurons is necessary for these events. Exposure to amphetamine in adolescence, but not in adulthood, leads to an increase in the span of dopamine innervation to the mPFC, but a reduction of presynaptic sites present on these axons. Amphetamine treatment in adolescence, but not in adulthood, also produces an increase in salience attribution to a previously drug-paired context in adulthood. Remarkably, DCC signaling within dopamine neurons is required for both of these effects. Drugs of abuse in adolescence may therefore induce their detrimental behavioral consequences by disrupting mesocortical dopamine development through alterations in the DCC signaling cascade.

  13. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2015-03-01

    Full Text Available Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC. Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

  14. Dorsal hippocampus and medial prefrontal cortex each contribute to the retrieval of a recent spatial memory in rats.

    Science.gov (United States)

    Cholvin, Thibault; Loureiro, Michaël; Cassel, Raphaelle; Cosquer, Brigitte; Herbeaux, Karin; de Vasconcelos, Anne Pereira; Cassel, Jean-Christophe

    2016-01-01

    Systems-level consolidation models propose that recent memories are initially hippocampus-dependent. When remote, they are partially or completely dependent upon the medial prefrontal cortex (mPFC). An implication of the mPFC in recent memory, however, is still debated. Different amounts of muscimol (MSCI 0, 30, 50, 80 and 250 ng in 1 µL PBS) were used to assess the impact of inactivation of the dorsal hippocampus (dHip) or the mPFC (targeting the prelimbic cortex) on a 24-h delayed retrieval of a platform location that rats had learned drug-free in a water maze. The two smallest amounts of MSCI (30 and 50 ng) did not affect recall, whatever the region. 80 ng MSCI infused into the dHip disrupted spatial memory retrieval, as did the larger amount. Infusion of MSCI into the mPFC did not alter performance in the 0-80 ng range. At 250 ng, it induced an as dramatic memory impairment as after efficient dHip inactivation. Stereological quantifications showed that 80 ng MSCI in the dHip and 250 ng MSCI in the mPFC induced a more than 80% reduction of c-Fos expression, suggesting that, beyond the amounts infused, it is the magnitude of the neuronal activity decrease which is determinant as to the functional outcome of the inactivation. Because, based on the literature, even 250 ng MSCI is a small amount, our results point to a contribution of the mPFC to the recall of a recently acquired spatial memory and thereby extend our knowledge about the functions of this major actor of cognition.

  15. Positively-valenced stimuli facilitate creative novel metaphoric processes by enhancing medial prefrontal cortical (mPFC activation

    Directory of Open Access Journals (Sweden)

    Karuna eSubramaniam

    2013-04-01

    Full Text Available A metaphor is a figure of speech in which a subject is symbolic of another unrelated object. In the present study, we examined neural patterns associated with both novel unfamiliar and conventional familiar metaphoric processing, and how these patterns are modulated by affective valence. Prior to fMRI scanning, participants received a list of word pairs (novel unfamiliar metaphors as well as conventional familiar metaphors and were asked to denote the valence (positive, negative, or neutral of each word pair. During scanning, participants had to decide whether the word pairs formed meaningful or meaningless expressions. Results indicate that participants were faster and more accurate at deciding that positively-valenced metaphors were meaningful compared to neutral metaphors. These behavioral findings were accompanied by increased activation in the medial prefrontal cortex (mPFC, posterior cingulate cortex (PCC, and the right inferior parietal lobe (IPL. Specifically, positively-valenced novel unfamiliar metaphors elicited activation in these brain regions in addition to the left superior temporal gyrus when compared to neutral novel metaphors. We also found that the mPFC and PCC mediated the processing of positively-valenced metaphors when compared to negatively-valenced metaphors. Positively-valenced conventional metaphors, however, elicited different neural signatures when contrasted with either neutral or negatively-valenced conventional metaphors. Together, our results indicate that positively-valenced stimuli facilitate creative metaphoric processes (specifically novel metaphoric processes by mediating attention and cognitive control processes required for the access, integration and selection of semantic associations via modulation of the mPFC. The present study is important for the development of neural accounts of emotion-cognition interactions required for creativity, language and successful social functioning in general.

  16. Defeat-induced activation of the ventral medial prefrontal cortex is necessary for resistance to conditioned defeat.

    Science.gov (United States)

    Morrison, Kathleen E; Bader, Lauren R; McLaughlin, Colleen N; Cooper, Matthew A

    2013-04-15

    The ventral medial prefrontal cortex (vmPFC) controls vulnerability to the negative effects of chronic or uncontrollable stress. Dominance status alters responses to social defeat in the conditioned defeat model, which is a model characterized by loss of territorial aggression and increased submissive and defensive behavior following an acute social defeat. We have previously shown that dominant individuals show a reduced conditioned defeat response and increased defeat-induced neural activation in the vmPFC compared to subordinates. Here, we tested the hypothesis that defeat-induced activation of the vmPFC is necessary to confer resistance to conditioned defeat in dominants. We paired weight-matched male Syrian hamsters (Mesocricetus auratus) in daily 5-min aggressive encounters for 2 weeks and identified dominants and subordinates. Twenty-four hours after the final pairing, animals were bilaterally injected with 200 nl of the GABAA receptor agonist muscimol (1.1 nmol) or 200 nl of saline vehicle 5 min prior to social defeat. Defeat consisted of 3, 5-min encounters with resident aggressor hamsters at 10-min intervals. Twenty-four hours following social defeat, animals received conditioned defeat testing which involved a 5-min social interaction test with a non-aggressive intruder. Muscimol injection prior to social defeat prevented the reduced conditioned defeat response observed in vehicle-treated dominants. Further, there was no effect of muscimol injection on the conditioned defeat response in subordinates or controls. These data support the conclusion that activation of the vmPFC during social defeat is necessary for the protective effects of dominant social status on the acquisition of conditioned defeat.

  17. The medial prefrontal cortex is crucial for the maintenance of persistent licking and the expression of incentive contrast

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    Marc Alexander Parent

    2015-03-01

    Full Text Available We examined the role of the medial prefrontal cortex (mPFC in reward processing and the control of consummatory behavior. Rats were trained in an operant licking procedure in which they received alternating access to solutions with relatively high and low levels of sucrose (20% and 4%, w/v. Each level of sucrose was available for fixed intervals of 30 seconds over 30 minute test sessions. Over several days of training, rats came to lick persistently when the high level of sucrose was available and suppressed licking when the low level of sucrose was available. Pharmacological inactivations of the mPFC, specifically the rostral part of the prelimbic area, greatly reduced intake of the higher value fluid and only slightly increased intake of the lower value fluid. In addition, the inactivations altered within-session patterns and microstructural measures of licking. Rats licked equally for the high and low levels of sucrose at the beginning of the test sessions and relearned to reduce intake of the low value fluid over the test sessions. Durations of licking bouts (clusters of licks with inter-lick intervals <0.5 sec were reduced for the high value fluid and there were many more brief licking bouts (<1 sec when the low value fluid was available. These effects were verified using an alternative approach (optogenetic silencing using archaerhodopsin and were distinct from inactivation of the ventral striatum, which simply increased overall intake. Our findings suggest that the mPFC is crucial for the maintenance of persistent licking and the expression of learned feeding strategies.

  18. Performance monitoring and the medial prefrontal cortex: A review of individual differences and context effects as a window on self-regulation

    Directory of Open Access Journals (Sweden)

    Stefon evan Noordt

    2012-07-01

    Full Text Available The medial prefrontal cortex (MPFC is central to self-regulation and has been implicated in generating a cluster of event-related potential components, collectively referred to as medial frontal negativities (MFNs. These MFNs are elicited while individuals monitor behavioural and environmental consequences, and include the error-related negativity, Nogo N2, and the feedback-related negativity. A growing cognitive and affective neuroscience literature indicates that the activation of the anterior cingulate cortex and surrounding medial prefrontal regions during performance monitoring is not only influenced by task context, but that these patterns of activity also vary as a function of individual differences (e.g., personality, temperament, clinical and non-clinical symptomatology, socio-political orientation, and genetic polymorphisms, as well as interactions between individual differences and task context. In this review we survey the neuroscience literature on the relations between performance monitoring, personality, task context, and brain functioning with a focus on the MPFC. We relate these issues to the role of affect in the paradigms used to elicit performance-monitoring neural responses and highlight some of the theoretical and clinical implications of this research. We conclude with a discussion of the complexity of these issues and how some of the basic assumptions required for their interpretation may be clarified with future research.

  19. Habitual 'sleep credit' is associated with greater grey matter volume of the medial prefrontal cortex, higher emotional intelligence and better mental health.

    Science.gov (United States)

    Weber, Mareen; Webb, Christian A; Deldonno, Sophie R; Kipman, Maia; Schwab, Zachary J; Weiner, Melissa R; Killgore, William D S

    2013-10-01

    In modern society, people often fail to obtain the amount of sleep that experts recommend for good health and performance. Insufficient sleep can lead to degraded cognitive performance and alterations in emotional functioning. However, most people also acknowledge that on a regular basis they obtain more sleep than they subjectively perceive they need at a minimum to stave off performance decrements, a construct we describe as subjective 'sleep credit'. Few people would contest the notion that getting more sleep is better, but data on both behavioural and neuroanatomical correlates of 'sleep credit' are surprisingly limited. We conducted a voxel-based morphometric study to assess cerebral grey matter correlates of habitually sleeping more than one's subjective requirements. We further tested whether these structural correlates are associated with perceived emotional intelligence and indices of psychopathology while controlling for age, gender, and total intracranial volume. In a sample of 55 healthy adults aged 18-45 years (28 males, 27 females), whole-brain multiple regression showed that habitual subjective 'sleep credit' was correlated positively with grey matter volume within regions of the left medial prefrontal cortex and right orbitofrontal gyrus. Volumes were extracted and regressed against self-report emotion and psychopathology indices. Only grey matter volume of the medial prefrontal cortex cluster correlated with greater emotional intelligence and lower scores on several indices of psychopathology. Findings converge with previous evidence of the role of the medial prefrontal cortex in the relationship between sleep and emotional functioning, and suggest that behaviour and brain structure vary with habitual 'sleep credit'.

  20. Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats

    OpenAIRE

    2012-01-01

    Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express green fluorescent protein (GFP) in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained...

  1. Diazepam-Induced Increases of Synaptic Efficacy in the Hippocampal-Medial Prefrontal Cortex Pathway Are Associated With Its Anxiolytic-like Effect in Rats

    OpenAIRE

    2010-01-01

    The medial prefrontal cortex (mPFC) has recently been shown to be an important brain region for emotional function as well as cognitive ability. In previous experiments, we studied the population spike amplitude (PSA) in the mPFC induced by stimulation of the CA1/subicular region as an index of synaptic efficacy in the hippocampal-mPFC pathway. In the present study, we investigated the relationship between the anxiolytic effect of diazepam and the changes of synaptic efficacy in this pathway....

  2. Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder.

    Science.gov (United States)

    Meier, Timothy B; Drevets, Wayne C; Wurfel, Brent E; Ford, Bart N; Morris, Harvey M; Victor, Teresa A; Bodurka, Jerzy; Teague, T Kent; Dantzer, Robert; Savitz, Jonathan

    2016-03-01

    Reductions in gray matter volume of the medial prefrontal cortex (mPFC), especially the rostral and subgenual anterior cingulate cortex (rACC, sgACC) are a widely reported finding in major depressive disorder (MDD). Inflammatory mediators, which are elevated in a subgroup of patients with MDD, activate the kynurenine metabolic pathway and increase production of neuroactive metabolites such as kynurenic acid (KynA), 3-hydroxykynurenine (3HK) and quinolinic acid (QA) which influence neuroplasticity. It is not known whether the alterations in brain structure and function observed in major depressive disorders are due to the direct effect of inflammatory mediators or the effects of neurotoxic kynurenine metabolites. Here, using partial posterior predictive distribution mediation analysis, we tested whether the serum concentrations of kynurenine pathway metabolites mediated reductions in cortical thickness in mPFC regions in MDD. Further, we tested whether any association between C-reactive protein (CRP) and cortical thickness would be mediated by kynurenine pathway metabolites. Seventy-three unmedicated subjects who met DSM-IV-TR criteria for MDD and 91 healthy controls (HC) completed MRI scanning using a pulse sequence optimized for tissue contrast resolution. Automated cortical parcellation was performed using the PALS-B12 Brodmann area atlas as implemented in FreeSurfer in order to compare the cortical thickness and cortical area of six PFC regions: Brodmann areas (BA) 9, 10, 11, 24, 25, and 32. Serum concentrations of kynurenine pathway metabolites were determined by high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) detection, while high-sensitivity CRP concentration was measured immunoturbidimetrically. Compared with HCs, the MDD group showed a reduction in cortical thickness of the right BA24 (pdepressive episodes displayed thinner cortex in BA32 (p<0.05). Consistent with our previous findings in an overlapping sample, the KynA/3

  3. The medial prefrontal cortex-lateral entorhinal cortex circuit is essential for episodic-like memory and associative object-recognition.

    Science.gov (United States)

    Chao, Owen Y; Huston, Joseph P; Li, Jay-Shake; Wang, An-Li; de Souza Silva, Maria A

    2016-05-01

    The prefrontal cortex directly projects to the lateral entorhinal cortex (LEC), an important substrate for engaging item-associated information and relaying the information to the hippocampus. Here we ask to what extent the communication between the prefrontal cortex and LEC is critically involved in the processing of episodic-like memory. We applied a disconnection procedure to test whether the interaction between the medial prefrontal cortex (mPFC) and LEC is essential for the expression of recognition memory. It was found that male rats that received unilateral NMDA lesions of the mPFC and LEC in the same hemisphere, exhibited intact episodic-like (what-where-when) and object-recognition memories. When these lesions were placed in the opposite hemispheres (disconnection), episodic-like and associative memories for object identity, location and context were impaired. However, the disconnection did not impair the components of episodic memory, namely memory for novel object (what), object place (where) and temporal order (when), per se. Thus, the present findings suggest that the mPFC and LEC are a critical part of a neural circuit that underlies episodic-like and associative object-recognition memory.

  4. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    Energy Technology Data Exchange (ETDEWEB)

    Asensio, S.; Goldstein, R.; Asensio, S.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F..; Volkow, N.D.; Goldstein, R.Z.

    2010-05-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [{sup 11}C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

  5. Cognitive and affective theory of mind share the same local patterns of activity in posterior temporal but not medial prefrontal cortex

    Science.gov (United States)

    Hofstetter, Christoph; Vuilleumier, Patrik

    2014-01-01

    Understanding emotions in others engages specific brain regions in temporal and medial prefrontal cortices. These activations are often attributed to more general cognitive ‘mentalizing’ functions, associated with theory of mind and also necessary to represent people’s non-emotional mental states, such as beliefs or intentions. Here, we directly investigated whether understanding emotional feelings recruit similar or specific brain systems, relative to other non-emotional mental states. We used functional magnetic resonance imaging with multivoxel pattern analysis in 46 volunteers to compare activation patterns in theory-of-mind tasks for emotions, relative to beliefs or somatic states accompanied with pain. We found a striking dissociation between the temporoparietal cortex, that exhibited a remarkable voxel-by-voxel pattern overlap between emotions and beliefs (but not pain), and the dorsomedial prefrontal cortex, that exhibited distinct (and yet nearby) patterns of activity during the judgment of beliefs and emotions in others. Pain judgment was instead associated with activity in the supramarginal gyrus, middle cingulate cortex and middle insular cortex. Our data reveal for the first time a functional dissociation within brain networks sub-serving theory of mind for different mental contents, with a common recruitment for cognitive and affective states in temporal regions, and distinct recruitment in prefrontal areas. PMID:23770622

  6. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    Science.gov (United States)

    Asensio, Samuel; Romero, Maria J.; Romero, Francisco J.; Wong, Christopher; Alia-Klein, Nelly; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Volkow, Nora D.; Goldstein, Rita Z.

    2009-01-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to non-drug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [11C]raclopride and positron emission tomography and response to monetary reward was measured (an average of 3 years later) with functional magnetic resonance imaging in seven cocaine addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a non-drug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine addicted individuals. PMID:20034014

  7. Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism

    Directory of Open Access Journals (Sweden)

    Tania Rinaldi

    2008-10-01

    Full Text Available The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions in the brain, and stands in contrast to the hypo-functionality that is normally proposed in this region to explain some of the autistic symptoms. We propose that a number of deficits in autism such as sociability, attention, multi-tasking and repetitive behaviours, should be re-interpreted in the light of a hyper-functional prefrontal cortex.

  8. Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic Acid animal model of autism

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

    The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit...

  9. Blockade of IP[subscript 3]-Mediated SK Channel Signaling in the Rat Medial Prefrontal Cortex Improves Spatial Working Memory

    Science.gov (United States)

    Brennan, Avis R.; Dolinsky, Beth; Vu, Mai-Anh T.; Stanley, Marion; Yeckel, Mark F.; Arnsten, Amy F. T.

    2008-01-01

    Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP[subscript 3]-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP[subscript 3] receptor (IP[subscript…

  10. Early social isolation disrupts latent inhibition and increases dopamine D2 receptor expression in the medial prefrontal cortex and nucleus accumbens of adult rats.

    Science.gov (United States)

    Han, Xiao; Li, Nanxin; Xue, Xiaofang; Shao, Feng; Wang, Weiwen

    2012-04-04

    Adolescence is a critical period for neurodevelopment. In the present study, we investigated the effects of peri-adolescent social isolation on latent inhibition (LI) and dopamine D2 receptor expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) of young adult rats. Male Sprague-Dawley rats were randomly divided into adolescent isolation (ISO; isolated housing, 21-34 days of age) and social housing (SOC) groups. LI was tested at postnatal day 56. After behavioral testing, the number of dopamine D2 receptor-expressing cells was determined using immunohistochemistry. Adolescent social isolation impaired LI and increased the number of cells expressing the D2 receptor in the mPFC and NAc. The results suggest that adolescent social isolation produces profound effects on cognitive and dopaminergic function in adult rats, and could be used as an animal model of various neurodevelopmental disorders.

  11. Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

    Science.gov (United States)

    Mendoza, J; Sanio, C; Chaudhri, N

    2015-02-01

    The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03 nmol muscimol; 0.3 nmol baclofen; 0.3 μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted.

  12. Hippocampal activity is associated with self-descriptiveness effect in memory, whereas self-reference effect in memory depends on medial prefrontal activity.

    Science.gov (United States)

    Zhu, Lei; Guo, Xiuyan; Li, Jianqi; Zheng, Li; Wang, Qianfeng; Yang, Zhiliang

    2012-07-01

    The self has long been regarded as a unique cognitive structure by virtue of its superior mnemonic abilities. Two separate effects result from this self memory facilitation: self-reference effect and self-descriptiveness effect in memory. Self-reference effect denotes that information processed with reference to the self is better remembered than information processed with reference to others, whereas self-descriptiveness effect indicates that items judged to be self-relevant is remembered better than items judged not to be relevant to self during self-reference task. Although there is a compelling connection between self-reference effect in memory and self mentalization processes indexed by the medial prefrontal activity, the underlying mechanisms of the self-descriptiveness effect in memory have remained underspecified. In the present fMRI study, we used a subsequent memory paradigm to examine the neural correlates of self-descriptiveness and self-reference effect in memory. Participants encoded personality traits while performing self-reference and other-reference task (judged the descriptiveness of the traits to themselves or a famous person "Bruce Lee"), and then were given a test of recognition memory outside the scanner. It is revealed that the hippocampal activity corresponded with self-descriptiveness effect in memory, but the activity of the medial prefrontal cortex and perirhinal cortex related to self-reference effect in memory. These findings suggested that the memory boost for self-relevant items relies on the enhanced relational binding mechanisms employed during self-relevant items.

  13. Pilot Study of Response Inhibition and Error Processing in the Posterior Medial Prefrontal Cortex in Healthy Youth

    Science.gov (United States)

    Fitzgerald, Kate Dimond; Zbrozek, Christopher D.; Welsh, Robert C.; Britton, Jennifer C.; Liberzon, Israel; Taylor, Stephan F.

    2008-01-01

    Background: Recent neuroimaging work suggests that inhibitory and error processing in healthy adults share overlapping, but functionally distinct neural circuitries within the posterior medial frontal cortex (pMFC); however, it remains unknown whether the pMFC is differentially engaged by response inhibition compared to error commission in the…

  14. Medial prefrontal cortex dissociation between self and others in a referential task: an fMRI study based on word traits.

    Science.gov (United States)

    Yaoi, Ken; Osaka, Mariko; Osaka, Naoyuki

    2013-12-01

    A number of recent neuroimaging studies using self referential tasks have investigated whether self referential processing depends on a unique neural basis that operates specifically in the medial prefrontal cortex. However, these studies have provided contradictory results despite the use of similar methodologies. We hypothesized that these discrepancies are partially related to the task-difficulty that presents dissociations reaction times in the self- and other-referential tasks. We therefore measured brain activity during self and other referential tasks to determine if such activity can be dissociated according to the reaction times (fast versus slow) for the trait words. Activation differed across self and other only in the slow word condition. The self referential condition with slow reaction time produced greater activation in the ventromedial prefrontal cortex, whereas the other referential condition with slow reaction time produced activation of the middle temporal gyrus. Results suggested that the task-difficulty might affect whether or not brain activities within MPFC would be dissociated between self- and other-referential processing.

  15. Orexin/Hypocretin-1 Receptor Antagonism Selectively Reduces Cue-Induced Feeding in Sated Rats and Recruits Medial Prefrontal Cortex and Thalamus.

    Science.gov (United States)

    Cole, Sindy; Mayer, Heather S; Petrovich, Gorica D

    2015-11-05

    The orexin/hypocretin system is important for reward-seeking behaviors, however less is known about its function in non-homeostatic feeding. Environmental influences, particularly cues for food can stimulate feeding in the absence of hunger and lead to maladaptive overeating behavior. The key components of the neural network that mediates this cue-induced overeating in sated rats include lateral hypothalamus, amygdala, and medial prefrontal cortex (mPFC), yet the neuropharmacological mechanisms within this network remain unknown. The current study investigated a causal role for orexin in cue-driven feeding, and examined the neural substrates through which orexin mediates this effect. Systemic administration of the orexin-1 receptor (OX1R) antagonist SB-334867 had no effect on baseline eating, but significantly reduced cue-driven consumption in sated rats. Complementary neural analysis revealed that decreased cue-induced feeding under SB-334867 increased Fos expression in mPFC and paraventricular thalamus. These results demonstrate that OX1R signaling critically regulates cue-induced feeding, and suggest orexin is acting through prefrontal cortical and thalamic sites to drive eating in the absence of hunger. These findings inform our understanding of how food-associated cues override signals from the body to promote overeating, and indicate OX1R antagonism as a potential pharmacologic target for treatment of disordered eating in humans.

  16. Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform nuclei of the prefrontal cortex in a chronic restraint stress mouse model of depression.

    Science.gov (United States)

    Leem, Yea-Hyun; Yoon, Sang-Sun; Kim, Yu-Han; Jo, Sangmee Ahn

    2014-09-19

    Depression is one of the most prevalent mental illnesses, and causes a constant feeling of sadness and lose of interest, which often leads to suicide. Evidence suggests that depression is associated with aberrant MEK/ERK signaling. However, studies on MEK/ERK signaling in depression have only been done in a few brain regions, such as the hippocampus and mesolimbic reward pathways. Recent studies also implicate the involvement of the prefrontal cortex in depression. Thus, we examined the changes in MEK/ERK signaling in subregions of the prefrontal cortex of C57BL/6 mice by immunohistochemistry using phospho-MEK1/2 (Ser 217/221) and ERK1/2 (Thr202/Tyr204) antibodies. Mice were subjected to 21 consecutive days of restraint stress (for 2h daily), and depression-like behavior was evaluated using a sociability test and tail suspension test. The antidepressant, imipramine (20mg/kg) was injected intraperitoneally 30min before restraint stress exposure. Chronic/repeated restraint stress produced depressive-like behavior, such as increased social avoidance in the social interaction test, and enhanced immobility time in the tail suspension test. This depressive behavior was ameliorated by imipramine. The behavioral changes well corresponded to a decrease in MEK/ERK immunoreactivity in the medial orbital (MO) cortex and dorsal endopiriform nuclei (DEn), which was averted by imipramine, but not in cingulate, prelimbic, infralimbic, and motor cortex. These results suggest that MEK/ERK signaling is disrupted in the DEn and MO subregions of the prefrontal cortex in the depressive phenotype, and that blocking a decrease in activated MEK/ERK is inherent to the antidepressant imipramine response.

  17. Organización celular del área 10 de la corteza orbitofrontal del ser humano

    Directory of Open Access Journals (Sweden)

    Hernán J. Pimienta J.

    2005-03-01

    Full Text Available La región orbital del área 10 de la corteza cerebral del humano se relaciona con la disociación de la atención, la introspección, la monitorización individuo-ambiente y la memoria prospectiva.  Los estudios imaginológicos funcionales han identificado asimetrías en la actividad prefrontal.  Los correlatos celulares de estas asimetrías son desconocidos.

  18. Dihidrochalconas en corteza de iryanthera laevis

    Directory of Open Access Journals (Sweden)

    Juan C. Martínez V.

    2010-07-01

    Full Text Available Del extracto bencénico de la corteza de Iryanthera laevis (Myristicaceae, se aislaron e identificaron cuatro dihidrochalconas que corresponden a: 2', 4'-dihidroxl-4,6'-dimetoxidihidrochalcona,2',4'-dihidroxi-3.4-metilenodioxi-6'-metoxidihidrochalcona, 2',4'-dihidroxi-3,4,6'-trimetoxidihidrochalcona y 3'-(1",4"-di-phidroxifenil-2",3"-dimetilbutil-2',4'-dihidroxi-4,6'-dimetoxidihidrochalcona. Las estructuras fueron establecidas por métodos espectroscópicos.

  19. NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus.

    Science.gov (United States)

    de Freitas, Renato Leonardo; Salgado-Rohner, Carlos José; Biagioni, Audrey Francisco; Medeiros, Priscila; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Coimbra, Norberto Cysne

    2014-06-01

    The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors.

  20. Desde la corteza auditiva a la cóclea: Progresos en el sistema eferente auditivo

    OpenAIRE

    Terreros H,Gonzalo; Wipe U,Bárbara; León I,Alex; Délano R,Paul H

    2013-01-01

    El sistema eferente auditivo está constituido por el sistema olivococlear y por vías descendentes que provienen de la corteza auditiva y se dirigen a la cóclea. El sistema olivococlear se divide en una porción medial y una lateral, con neuronas que inervan a las células ciliadas externas y a fibras del nervio auditivo respectivamente. El principal neurotransmisor de las sinapsis olivococleares es acetilcolina, y tanto las células ciliadas externas como las fibras del nervio auditivo poseen re...

  1. Characterization of excitatory and inhibitory neuron activation in the mouse medial prefrontal cortex following palatable food ingestion and food driven exploratory behavior

    Directory of Open Access Journals (Sweden)

    Ronald P Gaykema

    2014-07-01

    Full Text Available The medial prefrontal cortex (mPFC is implicated in aspects of executive function, that include the modulation of attentional and memory processes involved in goal selection. Food-seeking behavior has been shown to involve activation of the mPFC, both during the execution of strategies designed to obtain food and during the consumption of food itself. As these behaviors likely require differential engagement of the prefrontal cortex, we hypothesized that the pattern of neuronal activation would also be behavior dependent. In this study we describe, for the first time, the expression of Fos in different layers and cell types of the infralimbic/dorsal peduncular (IL/DP and prelimbic/anterior cingulate (PL/AC subdivisions of mouse mPFC following both the consumption of palatable food and following exploratory activity of the animal directed at obtaining food reward. While both manipulations led to increases of Fos expression in principal excitatory neurons relative to control, food-directed exploratory activity produced a significantly greater increase in Fos expression than observed in the food intake condition. Consequently, we hypothesized that mPFC interneuron activation would also be differentially engaged by these manipulations. Interestingly, Fos expression patterns differed substantially between treatments and interneuron subtype, illustrating how the differential engagement of subsets of mPFC interneurons depends on the behavioral state. In our experiments, both vasoactive intestinal peptide- and parvalbumin-expressing neurons showed enhanced Fos expression only during the food-dependent exploratory task and not during food intake. Conversely, elevations in arcuate and paraventricular hypothalamic fos expression were only observed following food intake and not following food driven exploration. Our data suggest that activation of select mPFC interneurons may be required to support high cognitive demand states while being dispensable during

  2. The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

    Science.gov (United States)

    Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

    2014-09-01

    Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function.

  3. Repeated exposure to amphetamine during adolescence alters inhibitory tone in the medial prefrontal cortex following drug re-exposure in adulthood

    Science.gov (United States)

    Cox, Charles L.; Gulley, Joshua M.

    2016-01-01

    Behavioral sensitization following repeated amphetamine (AMPH) exposure is associated with changes in GABA function in the medial prefrontal cortex (mPFC). In rats exposed to AMPH during adolescence compared to adulthood, there are unique patterns of sensitization that may reflect age-dependent differences in drug effects on prefrontal GABAergic function. In the current study, we used a sensitizing regimen of repeated AMPH exposure in adolescent and adult rats to determine if a post-withdrawal AMPH challenge would alter inhibitory transmission in the mPFC in a manner that depends on age of exposure. Male Sprague-Dawley rats were treated with saline or 3 mg/kg AMPH (i.p.) during adolescence [postnatal day (P) 27 to P45] or adulthood (P85 to P103) and were sacrificed either at similar ages in adulthood (~P133; Experiment 1) or after similar withdrawal times (3-4 weeks; Experiment 2). Spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in vitro from deep layer pyramidal cells in the mPFC using the whole-cell configuration. We found no effect of AMPH pre-exposure on baseline sIPSC frequency. Subsequent application of AMPH (25 μM) produced a stable increase in sIPSC frequency in controls, suggesting that AMPH increases inhibitory tone in the mPFC. However, AMPH failed to increase sIPSCs in adolescent- or adult-exposed rats. In Experiment 2, where withdrawal period was kept similar for both exposure groups, AMPH induced a suppression of sIPSC activity in adolescent-exposed rats. These results suggest that sensitizing treatment with AMPH during adolescence or adulthood dampens inhibitory influences on mPFC pyramidal cells, but potentially through different mechanisms. PMID:27085589

  4. Role of reuniens nucleus projections to the medial prefrontal cortex and to the hippocampal pyramidal CA1 area in associative learning.

    Directory of Open Access Journals (Sweden)

    Lyndell Eleore

    Full Text Available We studied the interactions between short- and long-term plastic changes taking place during the acquisition of a classical eyeblink conditioning and following high-frequency stimulation (HFS of the reuniens nucleus in behaving mice. Synaptic changes in strength were studied at the reuniens-medial prefrontal cortex (mPFC and the reuniens-CA1 synapses. Input/output curves and a paired-pulse study enabled determining the functional capabilities of the two synapses and the optimal intensities to be applied at the reuniens nucleus during classical eyeblink conditioning and for HFS applied to the reuniens nucleus. Animals were conditioned using a trace paradigm, with a tone as conditioned stimulus (CS and an electric shock to the trigeminal nerve as unconditioned stimulus (US. A single pulse was presented to the reuniens nucleus to evoke field EPSPs (fEPSPs in mPFC and CA1 areas during the CS-US interval. No significant changes in synaptic strength were observed at the reuniens-mPFC and reuniens-CA1 synapses during the acquisition of eyelid conditioned responses (CRs. Two successive HFS sessions carried out during the first two conditioning days decreased the percentage of CRs, without evoking any long-term potentiation (LTP at the recording sites. HFS of the reuniens nucleus also prevented the proper acquisition of an object discrimination task. A subsequent study revealed that HFS of the reuniens nucleus evoked a significant decrease of paired-pulse facilitation. In conclusion, reuniens nucleus projections to prefrontal and hippocampal circuits seem to participate in the acquisition of associative learning through a mechanism that does not required the development of LTP.

  5. Novelty, but not operant aversive learning, enhances Fos and Egr-1 expression in the medial prefrontal cortex and hippocampal areas of rats.

    Science.gov (United States)

    Yochiy, Angélica; Britto, Luiz R G; Hunziker, Maria H L

    2012-12-01

    Immediate early genes (IEG) are presumed to be activated in response to stress, novelty, and learning. Evidence supports the involvement of prefrontal and hippocampal areas in stress and learning, but also in the detection of novel events. This study examined whether a previous experience with shocks changes the pattern of Fos and Egr-1 expression in the medial prefrontal cortex (mPFC), the hippocampal cornus ammonis 1 (CA1), and dentate gyrus (DG) of adult male Wistar rats that learned to escape in an operant aversive test. Subjects previously exposed to inescapable footshocks that learned to escape from shocks were assigned to the treated group (EXP). Subjects from Group Novelty (NOV) rested undisturbed during treatment and also learned to escape in the test. The nonshock group (NSH) rested undisturbed in both sessions. Standard immunohistochemistry procedures were used to detect the proteins in brain sections. The results show that a previous experience with shocks changed the pattern of IEG expression, then demonstrating c-fos and egr-1 induction as experience-dependent events. Compared with NSH and EXP an enhanced Fos expression was detected in the mPFC and CA1 subfield of Group NOV, which also exhibited increased Egr-1 expression in the mPFC and DG in comparison to NSH. No differences were found in the DG for Fos, or in the CA1 for Egr-1. Novelty, and not the operant aversive escape learning, seems to have generated IEG induction. The results suggest novel stimuli as a possible confounding factor in studies on Fos and/or Egr-1 expression in aversive conditions.

  6. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure

    DEFF Research Database (Denmark)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo

    2017-01-01

    -field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact...... of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5 mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time......-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results...

  7. Evidence for Tonic Control by the GABAA Receptor of Extracellular D-Serine Concentrations in the Medial Prefrontal Cortex of Rodents

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    Asami Umino

    2017-08-01

    Full Text Available Endogenous D-serine is a putative dominant co-agonist for the N-methyl-D-aspartate glutamate receptor (NMDAR in the mammalian forebrain. Although the NMDAR regulates the higher order brain functions by interacting with various neurotransmitter systems, the possible interactions between D-serine and an extra-glutamatergic system largely remain elusive. For the first time, we show in the rat and mouse using an in vivo microdialysis technique that the extracellular D-serine concentrations are under tonic increasing control by a major inhibitory transmitter, GABA, via the GABAA (GABAAR in the medial prefrontal cortex (mPFC. Thus, an intra-mPFC infusion of a selective GABAAR antagonist, bicuculline (BIC, caused a concentration-dependent and reversible decrease in the extracellular levels of D-serine in the rat mPFC without affecting those of another intrinsic NMDAR coagonist, glycine and an NMDAR agonist, L-glutamate. The decreasing effects of BIC were eliminated by co-infusion of a selective GABAA agonist, muscimol (MUS and were mimicked by a GABAA antagonist, gabazine (GBZ. In contrast, selective blockade of the GABAB or homomeric ρGABAA (formerly GABAC receptor by saclofen or (1,2,5,6-tetrahydropyridin-4-yl-methylphosphinic acid (TPMPA, respectively, failed to downregulate the prefrontal extracellular D-serine levels. Moreover, the local BIC application attenuated the ability of NMDA given to the mPFC to increase the cortical extracellular concentrations of taurine, indicating the hypofunction of the NMDAR. Finally, in the mouse mPFC, the reduction of the extracellular D-serine levels by a local injection of BIC into the prefrontal portion was replicated, and was precluded by inhibition of the neuronal or glial activity by co-local injection with tetrodotoxin (TTX or fluorocitrate (Fluo, respectively. These findings suggest that the GABAAR-mediated regulation of the D-serine signaling may exert fine-tuning of the NMDAR function and require both

  8. Ventral medial prefrontal cortex and person evaluation: forming impressions of others varying in financial and moral status.

    Science.gov (United States)

    Cloutier, Jasmin; Gyurovski, Ivo

    2014-10-15

    The current study investigated ventromedial prefrontal cortex (VMPFC) activity during impression formation of individuals varying on distinct dimensions of social status. In a block-design functional magnetic resonance imaging (fMRI) experiment, participants were presented with photographs of faces paired with a colored background indicating their lower, same, or higher financial status, or lower, same, or higher moral status. Participants were asked to form an impression of the targets, but were not instructed to explicitly evaluate them based on social status. Building on previous findings (Cloutier, Ambady, Meagher, & Gabrieli, 2012), a region of interest analysis revealed the interaction of status dimension and level in VMPFC, finding not only preferential response to targets with higher compared to lower moral status as previously demonstrated, but also greater response to targets with lower compared to higher financial status. The implications of these results are discussed with an emphasis towards better understanding the impact of social status on social cognition and uncovering the neural substrates of person evaluation.

  9. The role of the posterior temporal and medial prefrontal cortices in mediating learning from romantic interest and rejection.

    Science.gov (United States)

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

    2014-09-01

    Romantic interest or rejection can be powerful incentives not merely for their emotional impact, but for their potential to transform, in a single interaction, what we think we know about another person--or ourselves. Little is known, though, about how the brain computes expectations for, and learns from, real-world romantic signals. In a novel "speed-dating" paradigm, we had participants meet potential romantic partners in a series of 5-min "dates," and decide whether they would be interested in seeing each partner again. Afterward, participants were scanned with functional magnetic resonance imaging while they were told, for the first time, whether that partner was interested in them or rejected them. Expressions of interest and rejection activated regions previously associated with "mentalizing," including the posterior superior temporal sulcus (pSTS) and rostromedial prefrontal cortex (RMPFC); while pSTS responded to differences from the participant's own decision, RMPFC responded to prediction errors from a reinforcement-learning model of personal desirability. Responses in affective regions were also highly sensitive to participants' expectations. Far from being inscrutable, then, responses to romantic expressions seem to involve a quantitative learning process, rooted in distinct sources of expectations, and encoded in neural networks that process both affective value and social beliefs.

  10. Interactions of the dorsal hippocampus, medial prefrontal cortex and nucleus accumbens in formation of fear memory: difference in inhibitory avoidance learning and contextual fear conditioning.

    Science.gov (United States)

    Yang, Fang-Chi; Liang, K C

    2014-07-01

    Learning active or reactive responses to fear involves different brain circuitry. This study examined how the nuclus accumbens (NAc), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) may interact in memory processing for these two kinds of responses. Male Wistar rats with cannulae implanted in these areas were trained on a contextual fear conditioning or inhibitory avoidance task that respectively engaged a reactive or active response to fear in the test. Immediately after training, a memory modulating factor released by stress, norepinephrine (NE), was infused into one region and 4% lidocaine into another to examine if an upstream activation effect could be blocked by the downstream suppression. Retention tested 1 day later showed that in both tasks posttraining infusion of NE at different doses into either the DH or mPFC enhanced retention but the enhancement was blocked by concurrent infusion of lidocaine into the other region, suggesting reliance of the effect on functional integrity of both regions. Further, posttraining intra-NAc lidocaine infusion attenuated memory enhancement of NE infused to the DH or mPFC in the inhibitory avoidance task but did not do so in contextual fear conditioning. These results suggest that NE regulation of memory formation for the reactive and active responses to fear may rely on distinct interactions among the DH, mPFC and NAc. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Increased Hippocampus-Medial Prefrontal Cortex Resting-State Functional Connectivity and Memory Function after Tai Chi Chuan Practice in Elder Adults.

    Science.gov (United States)

    Tao, Jing; Liu, Jiao; Egorova, Natalia; Chen, Xiangli; Sun, Sharon; Xue, Xiehua; Huang, Jia; Zheng, Guohua; Wang, Qin; Chen, Lidian; Kong, Jian

    2016-01-01

    Previous studies provide evidence that aging is associated with the decline of memory function and alterations in the hippocampal (HPC) function, including functional connectivity to the medial prefrontal cortex (mPFC). In this study, we investigated if longitudinal (12-week) Tai Chi Chuan and Baduanjin practice can improve memory function and modulate HPC resting-state functional connectivity (rs-FC). Memory function measurements and resting-state functional magnetic resonance imaging (rs-fMRI) were applied at the beginning and the end of the experiment. The results showed that (1) the memory quotient (MQ) measured by the Wechsler Memory Scale-Chinese Revision significantly increased after Tai Chi Chuan and Baduanjin practice as compared with the control group, and no significant difference was observed in MQ between the Tai Chi Chuan and Baduanjin groups; (2) rs-FC between the bilateral hippocampus and mPFC significantly increased in the Tai Chi Chuan group compared to the control group (also in the Baduanjin group compared to the control group, albeit at a lower threshold), and no significant difference between the Tai Chi Chuan and Baduanjin groups was observed; (3) rs-FC increases between the bilateral hippocampus and mPFC were significantly associated with corresponding memory function improvement across all subjects. Similar results were observed using the left or right hippocampus as seeds. Our results suggest that both Tai Chi Chuan and Baduanjin may be effective exercises to prevent memory decline during aging.

  12. Increased hippocampus–medial prefrontal cortex resting state functional connectivity and memory function after Tai Chi Chuan practice in elder adults

    Directory of Open Access Journals (Sweden)

    Jing eTao

    2016-02-01

    Full Text Available Previous studies provide evidence that aging is associated with the decline of memory function and alterations in the hippocampal function, including functional connectivity to the medial prefrontal cortex (mPFC. In this study, we investigated if longitudinal (12-week Tai Chi Chuan and Baduanjin practice can improve memory function and modulate hippocampal resting-state functional connectivity (rs-FC. Memory function measurements and resting state functional Magnetic Resonance Imaging (rs-fMRI were applied at the beginning and the end of the experiment. The results showed that 1 the memory quotient (MQ measured by the Wechsler Memory Scale (WMS-CR significantly increased after Tai Chi Chuan and Baduanjin practice as compared with the control group, and no significant difference was observed in MQ between the Tai Chi Chuan and Baduanjin groups; 2)rs-FC between the bilateral hippocampus and mPFC significantly increased in the Tai Chi Chuan group compared to the control group (also in the Baduanjin group compared to the control group, albeit at a lower threshold, and no significant difference between the Tai Chi Chuan and Baduanjin groups was observed; 3 rs-FC increases between the bilateral hippocampus and mPFC were significantly associated with corresponding memory function improvement across all subjects. Similar results were observed using the left or right hippocampus as seeds. Our results suggest that both Tai Chi Chuan and Baduanjin may be effective exercises to prevent memory decline during aging.

  13. Decreased response of interneurons in the medial prefrontal cortex to 5-HT₁A receptor activation in the rat 6-hydroxydopamine Parkinson model.

    Science.gov (United States)

    Zhang, Qiaojun; Wang, Shuang; Zhang, Lina; Zhang, Huan; Qiao, Hongfei; Niu, Xiaolin; Liu, Jian

    2014-08-01

    This study examined the response of interneurons in the medial prefrontal cortex (mPFC) to 5-HT1A receptor agonist 8-OH-DPAT and change in expression of 5-HT1A receptor on glutamate decarboxylase 67 (GAD67)-positive neurons in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc). Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT dose-dependently inhibited the firing rate of the interneurons at all doses tested in sham-operated rats. In 6-OHDA-lesioned rats, 8-OH-DPAT, at the same doses, also inhibited the firing rate of the interneurons, whereas the inhibition was significant only at a high cumulative dose. Furthermore, injection of 8-OH-DPAT into the mPFC inhibited the interneurons in sham-operated rats, while having no effect on firing rate of the interneurons in 6-OHDA-lesioned rats. In contrast to sham-operated rats, SNc lesion reduced the expression of 5-HT1A receptor on GAD67-positive neurons in the prelimbic cortex, a sub-region of the mPFC. Our results indicate that degeneration of the nigrostriatal pathway leads to decreased response of mPFC interneurons to 5-HT1A receptor activation, which attributes to the down-regulation of 5-HT1A receptor expression in these interneurons.

  14. Streptozotocin diabetic mice display depressive-like behavior and alterations in the structure, neurotransmission and plasticity of medial prefrontal cortex interneurons.

    Science.gov (United States)

    Castillo-Gómez, Esther; Coviello, Simona; Perez-Rando, Marta; Curto, Yasmina; Carceller, Héctor; Salvador, Alicia; Nacher, Juan

    2015-07-01

    Diabetes mellitus patients are at increased risk of developing depression, although the neurobiological bases of this comorbidity are not yet fully understood. These patients show CNS alterations, similar to those found in major depression, including changes in the structure and neurotransmission of excitatory neurons. However, although depressive patients and animal models also display alterations in inhibitory networks, little is known about the effects of diabetes on interneurons. Our main objective was to study the impact of diabetes on interneurons of the medial prefrontal cortex (mPFC), one of the regions most affected by major depression. For this purpose we have induced diabetes with high-dose streptozotozin in transgenic mice displaying fluorescent interneurons. These animals showed a depressive-like behavior (increased immobility time in tail suspension test) in parallel with reductions in interneuronal dendritic arborization and in the expression of GAD67, the enzyme that synthetizes the inhibitory neurotransmitter GABA. However, the levels of PSA-NCAM, a plasticity-related molecule exclusively expressed by interneurons in the mPFC, were unaltered in the different regions and layers of this cortical area. Interestingly, diabetic mice also showed increased levels of synaptophysin, a synaptic vesicle protein. These results indicate that the structure and neurotransmission of interneurons is altered in the mPFC of diabetic mice and suggest that these changes may play a key role in the depressive symptoms associated to diabetes.

  15. Effects of oxytocin on methamphetamine-induced conditioned place preference and the possible role of glutamatergic neurotransmission in the medial prefrontal cortex of mice in reinstatement.

    Science.gov (United States)

    Qi, Jia; Yang, Jing-Yu; Wang, Fang; Zhao, Ya-Nan; Song, Ming; Wu, Chun-Fu

    2009-04-01

    Accumulating evidence has shown the neuroactive properties of oxytocin (OT), a neurohypophyseal neuropeptide, and its ability to reduce the abuse potential of drugs. The present study investigated the effects of OT on the conditioned place preference (CPP) induced by methamphetamine (MAP, 2.0 mg/kg, i.p.) in mice and the possible role of glutamatergic neurotransmission in the reinstatement of CPP. The results showed that OT (0.1, 0.5, 2.5 microg, i.c.v.) significantly inhibited the acquisition and facilitated the extinction of MAP-induced CPP and abolished the reinstatement of CPP induced by restraint stress. This effect of OT could be attenuated by atosiban (Ato, 2.0 microg, i.c.v.), a selective OT-receptor antagonist. OT failed to block the expression and the reinstatement of CPP induced by MAP challenge. Extracellular glutamate (Glu) levels in the medial prefrontal cortex (mPFC) were determined using microdialysis coupled to a high-performance liquid chromatography (HPLC) with a fluorescence detection system. The results indicated that OT markedly inhibited extracellular Glu levels induced by restraint stress in CPP mice, but not those induced by MAP priming. Ato also attenuated the effects of OT on the changes in Glu levels. Therefore, these findings suggest that OT inhibits drug reward-related behaviors induced by MAP via the OT receptor, and OT blocks the reinstatement of CPP, at least partially, by interfering with the glutamatergic system in the mPFC.

  16. Reduction of glutamate release probability and the number of releasable vesicles are required for suppression of glutamatergic transmission by β1-adrenoceptors in the medial prefrontal cortex.

    Science.gov (United States)

    Luo, Fei; Guo, Nan-Nan; Li, Si-Hai; Tang, Hua; Liu, Ying; Zhang, Yu

    2014-08-01

    The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation and behavioral inhibition. Microinjection of β1-adrenoceptor (β1-AR) agonist into the PFC has been shown to impair PFC cognitive function. However, the underlying cellular and molecular mechanisms have not been determined yet. In the present study, we tested the hypothesis that β1-AR mediated modulation of excitatory synaptic transmission contributes to PFC dysfunction. We found that 1) the β1-AR agonist Dobutamine (Dobu) suppressed the amplitude evoked excitatory postsynaptic currents (eEPSCs). 2) Dobu induced a significant suppression of the frequency and amplitude of miniature EPSCs (mEPSCs). 3) Dobu-suppressed glutamate release was mediated via decreasing release probability and the number of releasable vesicles. 4) Dobu suppressed inward currents evoked by puff application of glutamate or NMDA via postsynaptic PKA-dependent pathway. The present study indicates that β1-AR activation suppresses excitatory synaptic transmission in medial PFC (mPFC) via both pre- and post-synaptic PKA-dependent mechanisms. Our results may provide a cellular and molecular mechanism that helps explain β1-AR-induced PFC dysfunction.

  17. Chronic gestational stress leads to depressive-like behavior and compromises medial prefrontal cortex structure and function during the postpartum period.

    Directory of Open Access Journals (Sweden)

    Benedetta Leuner

    Full Text Available Postpartum depression, which affects approximately 15% of new mothers, is associated with impaired mother-infant interactions and deficits in cognitive function. Exposure to stress during pregnancy is a major risk factor for postpartum depression. However, little is known about the neural consequences of gestational stress. The medial prefrontal cortex (mPFC is a brain region that has been linked to stress, cognition, maternal care, and mood disorders including postpartum depression. Here we examined the effects of chronic gestational stress on mPFC function and whether these effects might be linked to structural modifications in the mPFC. We found that in postpartum rats, chronic gestational stress resulted in maternal care deficits, increased depressive-like behavior, and impaired performance on an attentional set shifting task that relies on the mPFC. Furthermore, exposure to chronic stress during pregnancy reduced dendritic spine density on mPFC pyramidal neurons and altered spine morphology. Taken together, these findings suggest that pregnancy stress may contribute to postpartum mental illness and its associated symptoms by compromising structural plasticity in the mPFC.

  18. The default modes of reading: Modulation of posterior cingulate and medial prefrontal cortex connectivity associated with subjective and objective differences in reading experience

    Directory of Open Access Journals (Sweden)

    Jonathan eSmallwood

    2013-11-01

    Full Text Available Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN, has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN — the posterior cingulate (PCC and medial prefrontal cortex (aMPFC — was predictive of individual differences in reading effectiveness (better comprehension, superior and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension and benefits to reading (such as an on-task focus because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not.

  19. Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory.

    Science.gov (United States)

    Slaker, Megan; Churchill, Lynn; Todd, Ryan P; Blacktop, Jordan M; Zuloaga, Damian G; Raber, Jacob; Darling, Rebecca A; Brown, Travis E; Sorg, Barbara A

    2015-03-11

    Pyramidal neurons in the medial prefrontal cortex (mPFC) critically contribute to cocaine-seeking behavior in humans and rodents. Activity of these neurons is significantly modulated by GABAergic, parvalbumin-containing, fast-spiking interneurons, the majority of which are enveloped by specialized structures of extracellular matrix called perineuronal nets (PNNs), which are integral to the maintenance of many types of plasticity. Using a conditioned place preference (CPP) procedure, we found that removal of PNNs primarily from the prelimbic region of the mPFC of adult, male, Sprague Dawley rats impaired the acquisition and reconsolidation of a cocaine-induced CPP memory. This impairment was accompanied by a decrease in the number of c-Fos-positive cells surrounded by PNNs. Following removal of PNNs, the frequency of inhibitory currents in mPFC pyramidal neurons was decreased; but following cocaine-induced CPP, both frequency and amplitude of inhibitory currents were decreased. Our findings suggest that cocaine-induced plasticity is impaired by removal of prelimbic mPFC PNNs and that PNNs may be a therapeutic target for disruption of cocaine CPP memories.

  20. Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: additional evidence.

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    Lisboa, Sabrina F; Borges, Anna A; Nejo, Priscila; Fassini, Aline; Guimarães, Francisco S; Resstel, Leonardo B

    2015-06-03

    Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate ECB effects is associated with increase in AEA levels in several encephalic areas, including the prefrontal cortex (PFC). Activation of CB1 receptors by CB1 agonists injected directly into these areas is usually anxiolytic. However, depending on the encephalic region being investigated and on the stressful experiences, opposite effects were observed, as reported in the ventral HIP. In addition, contradictory results have been reported after CB1 activation in the dorsal HIP (dHIP). Therefore, in the present paper we have attempted to verify if directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion of the medial PFC (MPFC) and dHIP would produce different effects in two conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel conflict test (VCT). We observed that drugs which interfere with ECB reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors, suggesting that CB1 signaling in these brain regions modulates defensive responses to both innate and learned threatening stimuli. This data further strengthens previous results indicating modulation of hippocampal and MPFC activity via CB1 by ECBs, which could be therapeutically targeted to treat anxiety disorders.

  1. Diazepam-induced increases of synaptic efficacy in the hippocampal-medial prefrontal cortex pathway are associated with its anxiolytic-like effect in rats.

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    Shikanai, Hiroki; Izumi, Takeshi; Matsumoto, Machiko; Togashi, Hiroko; Yamaguchi, Taku; Yoshida, Takayuki; Yoshioka, Mitsuhiro

    2010-01-01

    The medial prefrontal cortex (mPFC) has recently been shown to be an important brain region for emotional function as well as cognitive ability. In previous experiments, we studied the population spike amplitude (PSA) in the mPFC induced by stimulation of the CA1/subicular region as an index of synaptic efficacy in the hippocampal-mPFC pathway. In the present study, we investigated the relationship between the anxiolytic effect of diazepam and the changes of synaptic efficacy in this pathway. In contextual fear conditioning tests, diazepam (0.1 mg/kg) was not effective for fear-related freezing behavior. At a dose of 0.5 mg/kg, diazepam decreased freezing behavior 20 min after administration, with no discernible effect 30 min after administration. In electrophysiological experiments, 0.1 mg/kg diazepam had no effect on the PSA in the mPFC. In contrast, 0.5 mg/kg diazepam increased the PSA in the mPFC within 30 min of administration; however, this PSA increase was attenuated over the 30-min period. Based on these results, we propose that the diazepam-induced PSA increase in the mPFC is associated with its anxiolytic-like effect.

  2. Curcumin and sertraline prevent the reduction of the number of neurons and glial cells and the volume of rats' medial prefrontal cortex induced by stress.

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    Noorafshan, Ali; Abdollahifar, Mohammad-Amin; Asadi-Golshan, Reza; Rashidian-Rashidabadi, Ali; Karbalay-Doust, Saied

    2014-01-01

    Chronic stress induces morphological changes in the neurons of several brain regions, including medial prefrontal cortex (mPFC). This region is involved in variety of behavioral tasks, including learning and memory. Our previous work showed that stress impaired function. The present work extends the earlier work to study mPFC in stressed and non-stressed rats with or without sertraline or curcumin treatments using stereological methods. Sertraline is a selective serotonin reuptake inhibitor and curcumin is the main ingredient of turmeric with neuroprotective effects. In this study, 42 male rats were randomly assigned to seven groups: stress + distilled water, stress + olive oil, stress + curcumin (100 mg/kg/day), stress + sertraline (10 mg/kg/day), curcumin, sertraline, and control groups. After 56 days, the right mPFC was removed. The volume of mPFC and its subdivisions and the total number of neurons and glia were estimated. The results showed ~8%, ~8%, and 24% decrease in the volume of the mPFC and its prelimbic and infralimbic subdivisions, respectively. However, the anterior cingulated cortex remained unchanged. Also, the total number of the neurons and glial cells was significantly reduced (11% and 5%, respectively) in stress (+distilled water or olive oil) group in comparison to the non-stressed rats (Psertraline and stress + curcumin groups in comparison to the non-treated stressed rats (Psertraline could prevent the stress-induced changes in mPFC.

  3. Transcranial Direct Current Stimulation over the Medial Prefrontal Cortex and Left Primary Motor Cortex (mPFC-lPMC) Affects Subjective Beauty but Not Ugliness.

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    Nakamura, Koyo; Kawabata, Hideaki

    2015-01-01

    Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions.

  4. Enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the medial prefrontal cortex is triggered by the expression of Fos protein in guinea pigs.

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    Zheng, Ya-Juan; Dong, Yu-Chen; Zhu, Chao; Zhao, Mei-Sheng

    2016-03-01

    Eyelid conditioning, including delay eyelid conditioning and trace eyelid conditioning, has been used extensively to study neural structures and mechanisms of learning and memory as a form of associative learning. In the present study, microcurrent electrical stimulation was used to stimulate the medial prefrontal cortex (mPFC) to induce delay eyelid conditioning in guinea pigs. The acquisition rate and relative latency of the conditioned eyelid response (CR) and the startle eyelid response (SR) were analyzed. The mPFC sites in the guinea pigs were examined under a light microscope following Nissl staining. In addition, the expression of Fos protein in neurons was detected using immunohistochemistry and western blot analysis. The results indicated that the acquisition rates of CR and SR were increased significantly (Pguinea pigs (Pguinea pigs was triggered by the expression of Fos protein. The observations of the present study further expand the understanding of conditioned reflexes and may aid future investigations into the formation of eyelid conditioning and the mechanisms underlying the circuit in various conditions.

  5. Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing

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    Tuomo eStarck

    2013-11-01

    Full Text Available In resting state fMRI studies of autism spectrum disorders (ASDs decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. Default mode network (DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered.

  6. Using vitamin E to prevent the impairment in behavioral test, cell loss and dendrite changes in medial prefrontal cortex induced by tartrazine in rats.

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    Rafati, Ali; Nourzei, Nasrin; Karbalay-Doust, Saied; Noorafshan, Ali

    2017-03-01

    Tartrazine is a food color that may adversely affect the nervous system. Vitamin E is a neuro-protective agent. This study aimed to evaluate the effects of tartrazine and vitamin E on the performance of rats in memory and learning tests as well as the structure of medial Prefrontal Cortex (mPFC). The rats were first divided into seven groups which received the followings for a period of seven weeks: distilled water, corn oil, vitamin E (100mg/kg/day), a low dose (50mg/kg/day) and a high dose (50mg/kg/day) of tartrazine with and without vitamin E. Behavioral tests were conducted and the brain was extracted for stereological methods The high dose of tartrazine decreased the exploration time of novel objects (PE plus tartrazine prevented the above-mentioned changes. An acceptable daily dose of tartrazine could induce impairment in spatial memory and dendrite structure. Moreover, a high dose of tartrazine may defect the visual memory, mPFC structure, the spatial memory and also cause dendrite changes. Vitamin E could prevent the behavioral and structural changes.

  7. Dissociation of attention in learning and action: Effects of lesions of the amygdala central nucleus, medial prefrontal cortex, and posterior parietal cortex

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    Maddux, Jean-Marie; Kerfoot, Erin C.; Chatterjee, Souvik; Holland, Peter C.

    2010-01-01

    Many associative learning theories assert that the predictive accuracy of events affects the allocation of attention to them. More reliable predictors of future events are usually more likely to control action based on past learning, but less reliable predictors are often more likely to capture attention when new information is acquired. Previous studies showed that a circuit that includes the amygdala central nucleus (CEA) and the cholinergic substantia innominata/nucleus basalis magnocellularis (SI/nBM) is important for both sustained attention guiding action in a five-choice serial reaction time (5CSRT) task, and for enhanced new learning about less predictive cues in a serial conditioning task. In this study, we found that lesions of the cholinergic afferents of the medial prefrontal cortex interfered with 5CSRT performance but not with surprise-induced enhancement of learning, whereas lesions of cholinergic afferents of posterior parietal cortex impaired the latter effects but did not affect 5CSRT performance. CEA lesions impaired performance in both tasks. These results are consistent with the view that CEA affects these distinct aspects of attention by influencing the activity of separate, specialized cortical regions, via its modulation of SI/nBM. PMID:17324051

  8. Functional interaction of medial mediodorsal thalamic nucleus but not nucleus accumbens with amygdala and orbital prefrontal cortex is essential for adaptive response selection after reinforcer devaluation.

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    Izquierdo, Alicia; Murray, Elisabeth A

    2010-01-13

    In nonhuman primates, reward-based decision making may be assessed through choices of objects overlying two different foods, one of which has been devalued by selective satiation. The most adaptive object choices yield the food of higher value. A large body of data identifies the amygdala and orbital prefrontal cortex (PFo) as neural mediators of adaptive responses to reinforcer devaluation. More recent work in nonhuman primates reveals the critical role of the medial, magnocellular portion of the mediodorsal nucleus of the thalamus (MDm) as well. Because both the nucleus accumbens (NA) and the MDm are anatomically related to the amygdala and PFo, and because both regions are implicated in reward processing, we tested whether either region necessarily interacts with the amygdala and PFo to mediate reinforcer devaluation effects. We used a crossed-disconnection design in which monkeys received amygdala and PFo lesions in one hemisphere combined with either NA or MDm lesions in the contralateral hemisphere. Monkeys that sustained NA disconnection, like controls, showed robust shifts in object choices in response to reinforcer devaluation. In contrast, monkeys that sustained MDm disconnection failed to adjust their object choices. Thus, MDm, but not NA, works together with the amygdala and PFo to support reward-based decision making.

  9. Amygdala functional connectivity with medial prefrontal cortex at rest predicts the positivity effect in older adults' memory.

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    Sakaki, Michiko; Nga, Lin; Mather, Mara

    2013-08-01

    As people get older, they tend to remember more positive than negative information. This age-by-valence interaction has been called "positivity effect." The current study addressed the hypotheses that baseline functional connectivity at rest is predictive of older adults' brain activity when learning emotional information and their positivity effect in memory. Using fMRI, we examined the relationship among resting-state functional connectivity, subsequent brain activity when learning emotional faces, and individual differences in the positivity effect (the relative tendency to remember faces expressing positive vs. negative emotions). Consistent with our hypothesis, older adults with a stronger positivity effect had increased functional coupling between amygdala and medial PFC (MPFC) during rest. In contrast, younger adults did not show the association between resting connectivity and memory positivity. A similar age-by-memory positivity interaction was also found when learning emotional faces. That is, memory positivity in older adults was associated with (a) enhanced MPFC activity when learning emotional faces and (b) increased negative functional coupling between amygdala and MPFC when learning negative faces. In contrast, memory positivity in younger adults was related to neither enhanced MPFC activity to emotional faces, nor MPFC-amygdala connectivity to negative faces. Furthermore, stronger MPFC-amygdala connectivity during rest was predictive of subsequent greater MPFC activity when learning emotional faces. Thus, emotion-memory interaction in older adults depends not only on the task-related brain activity but also on the baseline functional connectivity.

  10. Recognition of Mother's voice evokes metabolic activation in the medial prefrontal cortex and lateral thalamus of Octodon degus pups.

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    Braun, K; Poeggel, G

    2001-01-01

    In a variety of animal species, including primates, vocal communication is an essential part to establish and maintain social interactions, including the emotional bond between the newborn, its parents and siblings. The aim of this study in pups of the trumpet-tailed rat, Octodon degus, was to identify cortical and subcortical brain regions, which are involved in the perception of vocalizations uttered by the mother. In this species, which is characterized by an elaborated vocal repertoire, the (14C)-2-fluoro-deoxyglucose autoradiography was applied to measure region-specific metabolic activation in response to the presentation of a learned emotionally relevant acoustic stimulus, the maternal calls. Already at the age of eight days the precentral medial cortex, anterior cingulate cortex and the lateral thalamus could be identified by their enhanced metabolic activation in response to the presentation of the emotionally relevant maternal nursing calls, whereas other brain areas, such as the hippocampus and amygdala did not show stimulus-induced activation. Since in humans changes of activity patterns in relation to the emotional content of spoken language have been observed in similar brain regions, e.g. in the anterior cingulate cortex, Octodon degus may provide a suitable animal model to study the cellular and synaptic mechanisms underlying perception, production and processing of conspecific vocalizations.

  11. Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB/cJ mice.

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    Pham, T H; Mendez-David, I; Defaix, C; Guiard, B P; Tritschler, L; David, D J; Gardier, A M

    2017-01-01

    Unlike classic serotonergic antidepressant drugs, ketamine, an NMDA receptor antagonist, exhibits a rapid and persistent antidepressant (AD) activity, at sub-anaesthetic doses in treatment-resistant depressed patients and in preclinical studies in rodents. The mechanisms mediating this activity are unclear. Here, we assessed the role of the brain serotonergic system in the AD-like activity of an acute sub-anaesthetic ketamine dose. We compared ketamine and fluoxetine responses in several behavioral tests currently used to predict anxiolytic/antidepressant-like potential in rodents. We also measured their effects on extracellular serotonin levels [5-HT]ext in the medial prefrontal cortex (mPFCx) and brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus involved in emotional behavior, and on 5-HT cell firing in the DRN in highly anxious BALB/cJ mice. Ketamine (10 mg/kg i.p.) had no anxiolytic-like effect, but displayed a long lasting AD-like activity, i.e., 24 h post-administration, compared to fluoxetine (18 mg/kg i.p.). Ketamine (144%) and fluoxetine (171%) increased mPFCx [5-HT]ext compared to vehicle. Ketamine-induced AD-like effect was abolished by a tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA) pointing out the role of the 5-HT system in its behavioral activity. Interestingly, increase in cortical [5-HT]ext following intra-mPFCx ketamine bilateral injection (0.25 μg/side) was correlated with its AD-like activity as measured on swimming duration in the FST in the same mice. Furthermore, pre-treatment with a selective AMPA receptor antagonist (intra-DRN NBQX) blunted the effects of intra-mPFCx ketamine on both the swimming duration in the FST and mPFCx [5-HT]ext suggesting that the AD-like activity of ketamine required activation of DRN AMPA receptors and recruited the prefrontal cortex/brainstem DRN neural circuit in BALB/c mice. These results confirm a key role of cortical 5-HT release in ketamine's AD-like activity following the

  12. Activation of pyramidal neurons in mouse medial prefrontal cortex enhances food seeking behavior while reducing impulsivity in the absence of an effect on food intake

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    Daniel McAllister Warthen

    2016-03-01

    Full Text Available The medial prefrontal cortex (mPFC is involved in a wide range of executive cognitive functions, including reward evaluation, decision-making, memory extinction, mood, and task switching. Manipulation of the mPFC has been shown to alter food intake and food reward valuation, but whether exclusive stimulation of mPFC pyramidal neurons, which form the principle output of the mPFC, is sufficient to mediate food rewarded instrumental behavior is unknown. We sought to determine the behavioral consequences of manipulating mPFC output by exciting pyramidal neurons in mouse mPFC during performance of a panel of behavioral assays, focusing on food reward. We found that increasing mPFC pyramidal cell output using Designer Receptors Exclusively Activated by Designer Drugs (DREADD enhanced performance in instrumental food reward assays that assess food seeking behavior, while sparing effects in affect and food intake. Specifically, activation of mPFC pyramidal neurons enhanced operant responding for food reward, reinstatement of palatable food seeking, and suppression of impulsive responding for food reward. Conversely, activation of mPFC pyramidal neurons had no effect on unconditioned food intake, social interaction, or behavior in an open field. Furthermore, we found that behavioral outcome is influenced by the degree of mPFC activation, with a low drive sufficient to enhance operant responding and a higher drive required to alter impulsivity. Additionally, we provide data demonstrating that DREADD stimulation involves a nitric oxide synthase dependent pathway, similar to endogenous muscarinic M3 receptor stimulation, a finding that provides novel mechanistic insight into an increasingly widespread method of remote neuronal control.

  13. Delay discounting without decision-making: Medial prefrontal cortex and amygdala activations reflect immediacy processing and correlate with impulsivity and anxious-depressive traits

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    Vera eLudwig

    2015-10-01

    Full Text Available Humans value rewards less when these are delivered in the future as opposed to immediately, a phenomenon referred to as delay discounting. While delay discounting has been studied during the anticipation of rewards and in the context of intertemporal decision-making, little is known about its neural correlates in the outcome phase (during reward delivery and their relation to personality. Personality traits that have been associated with increased delay discounting include impulsivity and, potentially, anxious-depressive traits. Here we performed functional magnetic resonance imaging (fMRI in 72 healthy participants while they carried out a monetary incentive delay task with a delay manipulation. In sixty percent of the experimental trials, participants won rewards that differed in magnitude (0.05€, 0.50€ or 1€ and delay until delivery (immediately, 10 days, or 100 days. A factor analysis on questionnaires yielded two factors reflecting Impulsivity and Anxiety/Depression, which we used to examine potential relationships between personality and delay discounting. When winning a reward, medial prefrontal cortex (mPFC activation was higher for immediate compared to delayed rewards. Moreover, amygdala activation correlated with reward magnitude for immediate but not for delayed rewards. Amygdala activation to winning immediate rewards was higher in more impulsive participants, while mPFC activation to winning immediate rewards was higher in more anxious-depressed participants. Our results uncover neural correlates of delay discounting during reward delivery, and suggest that impulsivity and subclinical anxious-depressive traits are related to stronger neural responses for winning immediate relative to delayed rewards.

  14. Induction and requirement of gene expression in the anterior cingulate cortex and medial prefrontal cortex for the consolidation of inhibitory avoidance memory

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    Zhang Yue

    2011-01-01

    Full Text Available Abstract Background Memory consolidation is a process to stabilize short-term memory, generating long-term memory. A critical biochemical feature of memory consolidation is a requirement for gene expression. Previous studies have shown that fear memories are consolidated through the activation of gene expression in the amygdala and hippocampus, indicating essential roles of these brain regions in memory formation. However, it is still poorly understood whether gene expression in brain regions other than the amygdala/hippocampus is required for the consolidation of fear memory; however, several brain regions are known to play modulatory roles in fear memory formation. Results To further understand the mechanisms underlying the formation of fear memory, we first identified brain regions where gene expression is activated after learning inhibitory avoidance (IA by analyzing the expression of the immediately early genes c-fos and Arc as markers. Similarly with previous findings, the induction of c-fos and Arc expression was observed in the amygdala and hippocampus. Interestingly, we also observed the induction of c-fos and Arc expression in the medial prefrontal cortex (mPFC: prelimbic (PL and infralimbic (IL regions and Arc expression in the anterior cingulate cortex (ACC. We next examined the roles of these brain regions in the consolidation of IA memory. Consistent with previous findings, inhibiting protein synthesis in the hippocampus blocked the consolidation of IA memory. More importantly, inhibition in the mPFC or ACC also blocked the formation of IA memory. Conclusion Our observations indicated that the formation of IA memory requires gene expression in the ACC and mPFC as well as in the amygdala and hippocampus, suggesting essential roles of the ACC and mPFC in IA memory formation.

  15. Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats.

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    Cifani, Carlo; Koya, Eisuke; Navarre, Brittany M; Calu, Donna J; Baumann, Michael H; Marchant, Nathan J; Liu, Qing-Rong; Khuc, Thi; Pickel, James; Lupica, Carl R; Shaham, Yavin; Hope, Bruce T

    2012-06-20

    Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.

  16. The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

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    Lisa Y. Maeng

    2013-12-01

    Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

  17. Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

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    Novick, Andrew M; Forster, Gina L; Hassell, James E; Davies, Daniel R; Scholl, Jamie L; Renner, Kenneth J; Watt, Michael J

    2015-10-01

    Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat. We propose the functional consequence of this increased DAT expression is enhanced DA clearance and subsequently decreased infralimbic mPFC DA availability. To test this, in vivo chronoamperometry was used to measure changes in accumulation of the DA signal following DAT blockade, with increased DAT-mediated clearance being reflected by lower DA signal accumulation. Previously defeated rats and controls were pre-treated with the norepinephrine transporter (NET) inhibitor desipramine (20 mg/kg, ip.) to isolate infralimbic mPFC DA clearance to DAT, then administered the selective DAT inhibitor GBR-12909 (20 or 40 mg/kg, sc.). Sole NET inhibition with desipramine produced no differences in DA signal accumulation between defeated rats and controls. However, rats exposed to adolescent social defeat demonstrated decreased DA signal accumulation compared to controls in response to both doses of GBR-12909, indicating greater DAT-mediated clearance of infralimbic mPFC DA. These results suggest that protracted increases in infralimbic mPFC DAT function represent a mechanism by which adolescent social defeat stress produces deficits in adult mPFC DA activity and corresponding behavioral and cognitive dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Dynamic interaction between medial prefrontal cortex and nucleus accumbens as a function of both motivational state and reinforcer magnitude: A c-Fos immunocytochemistry study

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    Moscarello, Justin M.; Ben-Shahar, Osnat; Ettenberg, Aaron

    2007-01-01

    This study examined the effects of simultaneous variations in motivational state (food deprivation) and reinforcer magnitude (food presentation) on c-Fos immunoreactivity in the pre-and infralimbic medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) core and shell, and dorsal striatum. In the first experiment, c-Fos was reliably increased in pre- and infralimbic mPFC of animals 12- and 36-h compared to 0-h deprived. In the second experiment, a small meal (2.5g) selectively increased c-Fos immunoreactivity in both mPFC subdivisions of 36-h deprived animals, as well as in both NAcc subdivisions of 12-h deprived animals. Correlational analyses revealed a changing relationship between mPFC subregions and the NAcc compartments to which they project. In subjects 12-h deprived and allowed a small meal, c-Fos counts in prelimbic mPFC and NAcc core were positively correlated, as were those in infralimbic mPFC and NAcc shell (r = . 83 and .76, respectively). The opposite was true of animals 36-h deprived, with prelimbic mPFC/NAcc core and infralimbic mPFC/NAcc shell negatively correlated (r = -.85 and -.82, respectively). The third experiment examined the effects of unrestricted feeding (presentation of 20g food) after 0, 12, or 36-h deprivation. No differences between mean c-Fos counts were found, though prelimbic mPFC/NAcc core, and mPFC/NAcc shell were positively correlated in animals 36-h deprived (r = .76 and .89, respectively). These data suggest that the activity within the mPFC and NAcc, as well as the interaction between the two, change as a complex combinatorial function of motivational state and reinforcer magnitude. Section: Cognitive and Behavioral Neuroscience PMID:17706947

  19. Sevoflurane anesthesia induces neither contextual fear memory impairment nor alterations in local population connectivity of medial prefrontal cortex local field potentials networks in aged rats.

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    Xu, Xinyu; Zhang, Qian; Tian, Xin; Wang, Guolin

    2016-08-01

    Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. This study aimed to determine the effects of sevoflurane on contextual fear memory of aged rats and to characterize local population connectivity of local field potentials (LFPs) in medial prefrontal cortex (mPFC) of aged rats during contextual fear memory. Eighteen-month-old male SD rats were implanted with one multichannel electrode array in mPFC. The aged rats were divided into control group, sevoflurane group (1 MAC sevoflurane for 2 h) and surgical group with 1.0 MAC sevoflurane for 2 h. We then assessed the effect of the anesthesia on contextual fear memory, and alterations in the local population connectivity of mPFC LFP networks by partial directed coherence (PDC). Surgery impaired contextual fear memory and reduced local population connectivity of mPFC LFP networks in aged rats at day 1 after the surgery and anesthesia. 1 MAC Sevoflurane anesthesia induced neither contextual fear memory impairment nor alterations in local population connectivity of mPFC LFP networks in aged rats when tested 1, 7, 15 and 30 days after exposure (P > 0.05). PDC values of theta band mPFC LFPs became strongly increased during contextual fear memory at 1, 7, 15, and 30 days after anesthesia. Our results suggest that 1 MAC sevoflurane anesthesia does not induce contextual fear memory impairment in aged rats and suggest that the increased local population connectivity in theta bands LFPs of mPFC plays a role in contextual fear memory.

  20. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity.

    Science.gov (United States)

    Anastasio, Noelle C; Stutz, Sonja J; Fink, Latham H L; Swinford-Jackson, Sarah E; Sears, Robert M; DiLeone, Ralph J; Rice, Kenner C; Moeller, F Gerard; Cunningham, Kathryn A

    2015-07-15

    A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally relevant mechanism underlying motor impulsivity.

  1. Differential role of the dorsal hippocampus, ventro-intermediate hippocampus, and medial prefrontal cortex in updating the value of a spatial goal.

    Science.gov (United States)

    De Saint Blanquat, Paul; Hok, Vincent; Save, Etienne; Poucet, Bruno; Chaillan, Franck A

    2013-05-01

    Encoding of a goal with a specific value while performing a place navigation task involves the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC), and depends on the coordination between mPFC and the ventro-intermediate hippocampus (vHPC).The present work investigates the contribution of mPFC, dHPC, and vHPC when the rat has to update the value of a goal. Rats were trained to navigate to an uncued goal in order to release a food pellet in a continuous place navigation task. When they had reached criterion performance level in the task, they were subjected to a single "flash session" in which they were exposed to an aversive strobe light during goal visits instead of receiving a food reward. Just before the flash session, the GABA(A) agonist muscimol was injected to temporarily inactivate mPFC, dHPC, or vHPC. The ability to recall the changed value of the goal was tested on the next day. We first demonstrate the aversive effect of the strobe light by showing that rats learn to avoid the goal much more rapidly in the flash session than during a simple extinction session in which goal visits are not rewarded. Furthermore, while dHPC inactivation had no effect on learning and recalling the new goal value, vHPC muscimol injections considerably delayed goal value updating during the flash session, which resulted in a slight deficit during recall. In contrast, mPFC muscimol injections induced faster goal value updating but the rats were markedly impaired on recalling the new goal value on the next day. These results suggest that, contrary to mPFC and dHPC, vHPC is required for updating the value of a goal. In contrast, mPFC is necessary for long-term retention of this updating.

  2. Glycogen synthase kinase-3β inhibition in the medial prefrontal cortex mediates paradoxical amphetamine action in a mouse model of ADHD

    Directory of Open Access Journals (Sweden)

    Yi-Chun eYen

    2015-03-01

    Full Text Available Psychostimulants show therapeutic efficacy in the treatment of attention-deficit hyperactivity disorder (ADHD. It is generally assumed that they ameliorate ADHD symptoms via interfering with monoaminergic signaling. We combined behavioral pharmacology, neurochemistry and molecular analyses to identify mechanisms underlying the paradoxical calming effect of amphetamine in low trait anxiety behavior (LAB mice, a novel multigenetic animal model of ADHD. Amphetamine (1 mg/kg and methylphenidate (10 mg/kg elicited similar dopamine and norepinephrine release in the medial prefrontal cortex (mPFC and in the striatum of LAB mice. In contrast, amphetamine decreased, while methylphenidate increased locomotor activity. This argues against changes in dopamine and/or norepinephrine release as mediators of amphetamine paradoxical effects. Instead, the calming activity of amphetamine corresponded to the inhibition of glycogen synthase kinase3β (GSK3β activity, specifically in the mPFC. Accordingly, not only systemic administration of the GSK3β inhibitor TDZD-8 (20 mg/kg, but also local microinjections of TDZD-8 and amphetamine into the mPFC, but not into the striatum, decreased locomotor activity in LAB mice. Amphetamine effects seem to depend on NMDA receptor signaling, since pre- or co-treatment with MK-801 (0.3 mg/kg abolished the effects of amphetamine (1 mg/kg on the locomotion and on the phosphorylation of GSK3β at the level of the mPFC. Taken together, the paradoxical calming effect of amphetamine in hyperactive LAB mice concurs with a decreased GSK3β activity in the mPFC. This effect appears to be independent of dopamine or norepinephrine release, but contingent on NMDA receptor signaling.

  3. Impaired personal trait knowledge, but spared other-person trait knowledge, in an individual with bilateral damage to the medial prefrontal cortex.

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    Marquine, María J; Grilli, Matthew D; Rapcsak, Steven Z; Kaszniak, Alfred W; Ryan, Lee; Walther, Katrin; Glisky, Elizabeth L

    2016-08-01

    Functional neuroimaging has revealed that in healthy adults retrieval of personal trait knowledge is associated with increased activation in the medial prefrontal cortex (mPFC). Separately, neuropsychology has shown that the self-referential nature of memory can be disrupted in individuals with mPFC lesions. However, it remains unclear whether damage to the mPFC impairs retrieval of personal trait knowledge. Therefore, in this neuropsychological case study we investigated the integrity of personal trait knowledge in J.S., an individual who sustained bilateral damage to the mPFC as a result of an anterior communicating artery aneurysm. We measured both accuracy and consistency of J.S.'s personal trait knowledge as well as his trait knowledge of another, frequently seen person, and compared his performance to a group of healthy adults. Findings revealed that J.S. had severely impaired accuracy and consistency of his personal trait knowledge relative to control participants. In contrast, J.S.'s accuracy and consistency of other-person trait knowledge was intact in comparison to control participants. Moreover, J.S. showed a normal positivity bias in his trait ratings. These results, albeit based on a single case, implicate the mPFC as critical for retrieval of personal trait knowledge. Findings also cast doubt on the likelihood that the mPFC, in particular the ventral mPFC, is necessary for storage and retrieval of trait knowledge of other people. Therefore, this case study adds to a growing body of evidence that mPFC damage can disrupt the link between self and memory.

  4. Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake.

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    Warthen, Daniel M; Lambeth, Philip S; Ottolini, Matteo; Shi, Yingtang; Barker, Bryan Scot; Gaykema, Ronald P; Newmyer, Brandon A; Joy-Gaba, Jonathan; Ohmura, Yu; Perez-Reyes, Edward; Güler, Ali D; Patel, Manoj K; Scott, Michael M

    2016-01-01

    The medial prefrontal cortex (mPFC) is involved in a wide range of executive cognitive functions, including reward evaluation, decision-making, memory extinction, mood, and task switching. Manipulation of the mPFC has been shown to alter food intake and food reward valuation, but whether exclusive stimulation of mPFC pyramidal neurons (PN), which form the principle output of the mPFC, is sufficient to mediate food rewarded instrumental behavior is unknown. We sought to determine the behavioral consequences of manipulating mPFC output by exciting PN in mouse mPFC during performance of a panel of behavioral assays, focusing on food reward. We found that increasing mPFC pyramidal cell output using designer receptors exclusively activated by designer drugs (DREADD) enhanced performance in instrumental food reward assays that assess food seeking behavior, while sparing effects on affect and food intake. Specifically, activation of mPFC PN enhanced operant responding for food reward, reinstatement of palatable food seeking, and suppression of impulsive responding for food reward. Conversely, activation of mPFC PN had no effect on unconditioned food intake, social interaction, or behavior in an open field. Furthermore, we found that behavioral outcome is influenced by the degree of mPFC activation, with a low drive sufficient to enhance operant responding and a higher drive required to alter impulsivity. Additionally, we provide data demonstrating that DREADD stimulation involves a nitric oxide (NO) synthase dependent pathway, similar to endogenous muscarinic M3 receptor stimulation, a finding that provides novel mechanistic insight into an increasingly widespread method of remote neuronal control.

  5. The default modes of reading: modulation of posterior cingulate and medial prefrontal cortex connectivity associated with comprehension and task focus while reading.

    Science.gov (United States)

    Smallwood, Jonathan; Gorgolewski, Krzysztof J; Golchert, Johannes; Ruby, Florence J M; Engen, Haakon; Baird, Benjamin; Vinski, Melaina T; Schooler, Jonathan W; Margulies, Daniel S

    2013-01-01

    Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN), has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN-the posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC)-was predictive of individual differences in reading comprehension and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. Better comprehension was associated with greater functional connectivity with a region of the right insula. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension) and benefits to reading (such as an on-task focus) because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not.

  6. The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.

    Science.gov (United States)

    Maeng, Lisa Y; Shors, Tracey J

    2013-01-01

    Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD), indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA) is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL) and infralimbic (IL) subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. About 24 h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similarly to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful life

  7. Noradrenergic signaling in the medial prefrontal cortex and amygdala differentially regulates vicarious trial-and-error in a spatial decision-making task.

    Science.gov (United States)

    Amemiya, Seiichiro; Kubota, Natsuko; Umeyama, Nao; Nishijima, Takeshi; Kita, Ichiro

    2016-01-15

    In uncertain choice situations, we deliberately search and evaluate possible options before taking an action. Once we form a preference regarding the current situation, we take an action more automatically and with less deliberation. In rats, the deliberation process can be seen in vicarious trial-and-error behavior (VTE), which is a head-orienting behavior toward options at a choice point. Recent neurophysiological findings suggest that VTE reflects the rat's thinking about future options as deliberation, expectation, and planning when rats feel conflict. VTE occurs depending on the demand: an increase occurs during initial learning, and a decrease occurs with progression in learning. However, the brain circuit underlying the regulation of VTE has not been thoroughly examined. In situations in which VTE often appears, the medial prefrontal cortex (mPFC) and the amygdala (AMY) are crucial for learning and decision making. Our previous study reported that noradrenaline regulates VTE. Here, to investigate whether the mPFC and AMY are involved in regulation of VTE, we examined the effects of local injection of clonidine, an alpha2 adrenergic autoreceptor agonist, into either region in rats during VTE and choice behavior during a T-maze choice task. Injection of clonidine into either region impaired selection of the advantageous choice in the task. Furthermore, clonidine injection into the mPFC suppressed occurrence of VTE in the early phase of the task, whereas injection into the AMY inhibited the decrease in VTE in the later phase and thus maintained a high level of VTE throughout the task. These results suggest that the mPFC and AMY play a role in the increase and decrease in VTE, respectively, and that noradrenergic mechanisms mediate the dynamic regulation of VTE over experiences.

  8. The long-lasting antidepressant effects of rapastinel (GLYX-13) are associated with a metaplasticity process in the medial prefrontal cortex and hippocampus.

    Science.gov (United States)

    Burgdorf, J; Zhang, X-L; Weiss, C; Gross, A; Boikess, S R; Kroes, R A; Khan, M A; Burch, R M; Rex, C S; Disterhoft, J F; Stanton, P K; Moskal, J R

    2015-11-12

    Rapastinel (GLYX-13) is an N-methyl-d-aspartate receptor (NMDAR) modulator that has characteristics of a glycine site partial agonist. Rapastinel is a robust cognitive enhancer and facilitates hippocampal long-term potentiation (LTP) of synaptic transmission in slices. In human clinical trials, rapastinel has been shown to produce marked antidepressant properties that last for at least one week following a single dose. The long-lasting antidepressant effect of a single dose of rapastinel (3mg/kg IV) was assessed in rats using the Porsolt, open field and ultrasonic vocalization assays. Cognitive enhancement was examined using the Morris water maze, positive emotional learning, and contextual fear extinction tests. LTP was assessed in hippocampal slices. Dendritic spine morphology was measured in the dentate gyrus and the medial prefrontal cortex. Significant antidepressant-like or cognitive enhancing effects were observed that lasted for at least one week in each model. Rapastinel facilitated LTP 1day-2weeks but not 4weeks post-dosing. Biweekly dosing with rapastinel sustained this effect for at least 8weeks. A single dose of rapastinel increased the proportion of whole-cell NMDAR current contributed by NR2B-containing NMDARs in the hippocampus 1week post-dosing, that returned to baseline by 4weeks post-dosing. The NMDAR antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked the antidepressant-like effect of rapastinel 1week post dosing. A single injection of rapastinel also increased mature spine density in both brain regions 24h post-dosing. These data demonstrate that rapastinel produces its long-lasting antidepressant effects via triggering NMDAR-dependent processes that lead to increased sensitivity to LTP that persist for up to two weeks. These data also suggest that these processes led to the alterations in dendritic spine morphologies associated with the maintenance of long-term changes in synaptic plasticity associated with learning

  9. Early stage attenuation of phase amplitude coupling in the hippocampus and medial prefrontal cortex in a transgenic rat model of AD.

    Science.gov (United States)

    Bazzigaluppi, Paolo; Beckett, Tina L; Koletar, Margaret M; Lai, Aaron Y; Joo, Illsung L; Brown, Mary E; Carlen, Peter L; McLaurin, JoAnne; Stefanovic, Bojana

    2017-08-04

    Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of GABAergic signalling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABAA ) receptors subunits α1, α5 and δ, and glutamic acid decarboxylases (GAD65 and GAD67). Concomitant to amyloid deposition and tau hyperphosphorylation, low-gamma band power was strongly attenuated in the HPC and mPFC of TgF344-AD rats in comparison to those in non-transgenic littermates. In addition, the phase-amplitude coupling of the neuronal networks in both areas was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude in TgF344-AD animals. Finally, the gamma coherence between HPC and mPFC was attenuated as well. These results demonstrate significant neuronal network dysfunction at an early stage of AD-like pathology. This network dysfunction precedes the onset of cognitive deficits and is likely driven by Aβ and tau pathologies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Differential dorsal and ventral medial prefrontal representations of the implicit self modulated by individualism and collectivism: An fMRI study.

    Science.gov (United States)

    Harada, Tokiko; Li, Zhang; Chiao, Joan Y

    2010-01-01

    Individualism and collectivism, or self-construal style, refer to cultural values that influence how people think about themselves and their relation to the social and physical environment. Recent neuroimaging evidence suggests that cultural values of individualism and collectivism dynamically modulate neural response within cortical midline structures, such as the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), during explicit self-evaluation. However, it remains unknown whether cultural priming modulates neural response during self-evaluation due to explicit task demands. Here we investigated how cultural priming of self-construal style affects neural activity within cortical midline structures during implicit self-evaluation in bicultural individuals. Results indicate that ventral MPFC showed relatively less deactivation during implicit evaluation of both self- and father-relevant information as compared to control condition (e.g., information of an unfamiliar person), irrespective of cultural priming. By contrast, dorsal MPFC showed relatively less deactivation during implicit evaluation of father-relevant information, but not self-relevant information, as compared to control condition, only when they were primed with individualism. Furthermore, dorsal MPFC showed relatively less deactivation during implicit evaluation of father-relevant information as compared to self-relevant condition only when they were primed with individualism. Hence, our results indicate that cultural priming modulates neural response within dorsal, but not ventral, portions of MPFC in a stimulus-driven rather than task-driven manner. More broadly, these findings suggest that cultural values dynamically shape neural representations during the evaluation, rather than the detection, of self-relevant information.

  11. Protracted abstinence from chronic ethanol exposure alters the structure of neurons and expression of oligodendrocytes and myelin in the medial prefrontal cortex.

    Science.gov (United States)

    Navarro, A I; Mandyam, C D

    2015-05-01

    In rodents, chronic intermittent ethanol vapor exposure (CIE) produces alcohol dependence, alters the structure and activity of pyramidal neurons and decreases the number of oligodendroglial progenitors in the medial prefrontal cortex (mPFC). In this study, adult Wistar rats were exposed to seven weeks of CIE and were withdrawn from CIE for 21 days (protracted abstinence; PA). Tissue enriched in the mPFC was processed for Western blot analysis and Golgi-Cox staining to investigate the long-lasting effects of CIE on the structure of mPFC neurons and the levels of myelin-associated proteins. PA increased dendritic arborization within apical dendrites of pyramidal neurons. These changes occurred concurrently with hypophosphorylation of the N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) at Tyr-1472. PA increased myelin basic protein (MBP) levels which occurred concurrently with hypophosphorylation of the premyelinating oligodendrocyte bHLH transcription factor Olig2 in the mPFC. Given that PA is associated with increased sensitivity to stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and stress alters oligodendrocyte expression as a function of glucocorticoid receptor (GR) activation, the levels of total GR and phosphorylated GR were also evaluated. PA produced hypophosphorylation of the GR at Ser-232 without affecting expression of total protein. These findings demonstrate persistent and compensatory effects of ethanol in the mPFC long after cessation of CIE, including enhanced myelin production and impaired GR function. Collectively, these results suggest a novel relationship between oligodendrocytes and GR in the mPFC, in which stress may alter frontal cortex function in alcohol dependent subjects by promoting hypermyelination, thereby altering the cellular composition and white matter structure in the mPFC.

  12. Chronic stress alters the dendritic morphology of callosal neurons and the acute glutamate stress response in the rat medial prefrontal cortex.

    Science.gov (United States)

    Luczynski, Pauline; Moquin, Luc; Gratton, Alain

    2015-01-01

    We have previously reported that interhemispheric regulation of medial prefrontal cortex (PFC)-mediated stress responses is subserved by glutamate (GLU)- containing callosal neurons. Evidence of chronic stress-induced dendritic and spine atrophy among PFC pyramidal neurons led us to examine how chronic restraint stress (CRS) might alter the apical dendritic morphology of callosal neurons and the acute GLU stress responses in the left versus right PFC. Morphometric analyses of retrogradely labeled, dye-filled PFC callosal neurons revealed hemisphere-specific CRS-induced dendritic retraction; whereas significant dendritic atrophy occurred primarily within the distal arbor of left PFC neurons, it was observed within both the proximal and distal arbor of right PFC neurons. Overall, CRS also significantly reduced spine densities in both hemispheres with the greatest loss occurring among left PFC neurons, mostly at the distal extent of the arbor. While much of the overall decrease in dendritic spine density was accounted by the loss of thin spines, the density of mushroom-shaped spines, despite being fewer in number, was halved. Using microdialysis we found that, compared to controls, basal PFC GLU levels were significantly reduced in both hemispheres of CRS animals and that their GLU response to 30 min of tail-pinch stress was significantly prolonged in the left, but not the right PFC. Together, these findings show that a history of chronic stress alters the dendritic morphology and spine density of PFC callosal neurons and suggest a mechanism by which this might disrupt the interhemispheric regulation of PFC-mediated responses to subsequent stressors.

  13. Fluoxetine prevents development of an early stress-related molecular signature in the rat infralimbic medial prefrontal cortex. Implications for depression?

    Directory of Open Access Journals (Sweden)

    Barreto Rafael A

    2012-10-01

    Full Text Available Abstract Background Psychological stress, particularly in chronic form, can lead to mood and cognitive dysfunction and is a major risk factor in the development of depressive states. How stress affects the brain to cause psychopathologies is incompletely understood. We sought to characterise potential depression related mechanisms by analysing gene expression and molecular pathways in the infralimbic medial prefrontal cortex (ILmPFC, following a repeated psychological stress paradigm. The ILmPFC is thought to be involved in the processing of emotionally contextual information and in orchestrating the related autonomic responses, and it is one of the brain regions implicated in both stress responses and depression. Results Genome-wide microarray analysis of gene expression showed sub-chronic restraint stress resulted predominantly in a reduction in transcripts 24 hours after the last stress episode, with 239 genes significantly decreased, while just 24 genes had increased transcript abundance. Molecular pathway analysis using DAVID identified 8 pathways that were significantly enriched in the differentially expressed gene list, with genes belonging to the brain-derived neurotrophic factor – neurotrophin receptor tyrosine kinase 2 (BDNF-Ntrk2 pathway most enriched. Of the three intracellular signalling pathways that are downstream of Ntrk2, real-time quantitative PCR confirmed that only the PI3K-AKT-GSK3B and MAPK/ERK pathways were affected by sub-chronic stress, with the PLCγ pathway unaffected. Interestingly, chronic antidepressant treatment with the selective serotonin reuptake inhibitor, fluoxetine, prevented the stress-induced Ntrk2 and PI3K pathway changes, but it had no effect on the MAPK/ERK pathway. Conclusions These findings indicate that abnormal BDNF-Ntrk2 signalling may manifest at a relatively early time point, and is consistent with a molecular signature of depression developing well before depression-like behaviours occur

  14. Dopamine, Noradrenaline and Differences in Sexual Behavior between Roman High and Low Avoidance Male Rats: A Microdialysis Study in the Medial Prefrontal Cortex

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    Sanna, Fabrizio; Bratzu, Jessica; Piludu, Maria A.; Corda, Maria G.; Melis, Maria R.; Giorgi, Osvaldo; Argiolas, Antonio

    2017-01-01

    Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline (NA) also, increase in the dialysate from the medial prefrontal cortex (mPFC) of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite 3,4-dihydroxyphenylacetic acid, DOPAC) and NA were found in both sexually naïve and experienced animals, but they were higher: (i) in RHA than in RLA rats; and (ii) in sexually experienced RHA and RLA rats than in their naïve counterparts. Finally, the differences in dopamine and NA in the mPFC occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naïve and experienced conditions. These results suggest that a higher dopaminergic tone also occurs in the mPFC, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the mesolimbic dopaminergic system. PMID:28638325

  15. Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors.

    Science.gov (United States)

    Devroye, Céline; Haddjeri, Nasser; Cathala, Adeline; Rovera, Renaud; Drago, Filippo; Piazza, Pier Vincenzo; Artigas, Francesc; Spampinato, Umberto

    2017-06-01

    Recent studies have shown that serotonin2B receptor (5-HT2BR) antagonists exert opposite facilitatory and inhibitory effects on dopamine (DA) release in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc), respectively, thereby leading to the proposal that these compounds could provide an interesting pharmacological tool for treating schizophrenia. Although the mechanisms underlying these effects remain unknown, several data in the literature suggest that 5-HT1ARs located into the mPFC could participate in this interaction. The present study, using in vivo microdialysis and electrophysiological recordings in rats, assessed this hypothesis by means of two selective 5-HT1AR (WAY 100635) and 5-HT2BR (RS 127445) antagonists. WAY 100635, administered either subcutaneously (0.16 mg/kg, s.c) or locally into the mPFC (0.1 μM), blocked the changes of mPFC and NAc DA release induced by the intraperitoneal administration of RS 127445 (0.16 mg/kg, i.p.). The administration of RS 127445 (0.16 mg/kg, i.p.) increased both dorsal raphe nucleus (DRN) 5-HT neuron firing rate and 5-HT outflow in the mPFC. Likewise, mPFC 5-HT outflow was increased following the intra-DRN injection of RS 127445 (0.032 μg/0.2 μl). Finally, intra-DRN injection of RS 127445 increased and decreased DA outflow in the mPFC and the NAc, respectively, these effects being reversed by the intra-mPFC perfusion of WAY 100635. These results demonstrate the existence of a functional interplay between mPFC 5-HT1ARs and DRN 5-HT2BRs in the control of the DA mesocorticolimbic system, and highlight the clinical interest of this interaction, as both receptors represent an important pharmacological target for the treatment of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Polysialic acid is required for dopamine D2 receptor-mediated plasticity involving inhibitory circuits of the rat medial prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Esther Castillo-Gómez

    Full Text Available Decreased expression of dopamine D2 receptors (D2R, dysfunction of inhibitory neurotransmission and impairments in the structure and connectivity of neurons in the medial prefrontal cortex (mPFC are involved in the pathogenesis of schizophrenia and major depression, but the relationship between these changes remains unclear. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM, a plasticity-related molecule, may serve as a link. This molecule is expressed in cortical interneurons and dopamine, via D2R, modulates its expression in parallel to that of proteins related to synapses and inhibitory neurotransmission, suggesting that D2R-targeted antipsychotics/antidepressants may act by affecting the plasticity of mPFC inhibitory circuits. To understand the role of PSA-NCAM in this plasticity, rats were chronically treated with a D2R agonist (PPHT after cortical PSA depletion. PPHT-induced increases in GAD67 and synaptophysin (SYN neuropil expression were blocked when PSA was previously removed, indicating a role for PSA-NCAM in this plasticity. The number of PSA-NCAM expressing interneuron somata also increased after PPHT treatment, but the percentages of these cells belonging to different interneuronal subpopulations did not change. Cortical pyramidal neurons did not express PSA-NCAM, but puncta co-expressing this molecule and parvalbumin could be found surrounding their somata. PPHT treatment increased the number of PSA-NCAM and parvalbumin expressing perisomatic puncta, but decreased the percentage of parvalbumin puncta that co-expressed SYN. PSA depletion did not block these effects on the perisomatic region, but increased further the number of parvalbumin expressing puncta and increased the percentage of puncta co-expressing SYN and parvalbumin, suggesting that the polysialylation of NCAM may regulate perisomatic inhibition of mPFC principal neurons. Summarizing, the present results indicate that dopamine acting on D2R

  17. Differential Local Connectivity and Neuroinflammation Profiles in the Medial Prefrontal Cortex and Hippocampus in the Valproic Acid Rat Model of Autism.

    Science.gov (United States)

    Codagnone, Martín Gabriel; Podestá, María Fernanda; Uccelli, Nonthué Alejandra; Reinés, Analía

    2015-01-01

    Autism spectrum disorders (ASD) are a group of developmental disabilities characterized by impaired social interaction, communication deficit and repetitive and stereotyped behaviors. Neuroinflammation and synaptic alterations in several brain areas have been suggested to contribute to the physiopathology of ASD. Although the limbic system plays an important role in the functions found impaired in ASD, reports on these areas are scarce and results controversial. In the present study we searched in the medial prefrontal cortex (mPFC) and hippocampus of rats exposed to the valproic acid (VPA) model of ASD for early structural and molecular changes, coincident in time with the behavioral alterations. After confirming delayed growth and maturation in VPA rats, we were able to detect decreased exploratory activity and social interaction at an early time point (postnatal day 35). In mPFC, although typical cortical column organization was preserved in VPA animals, we found that interneuronal space was wider than in controls. Hippocampal CA3 (cornu ammonis 3) pyramidal layer and the granular layer of the dentate gyrus both showed a disorganized spatial arrangement in VPA animals. Neuronal alterations were accompanied with increased tomato lectin and glial fibrillary acidic protein (GFAP) immunostainings both in the mPFC and hippocampus. In the latter region, the increased GFAP immunoreactivity was CA3 specific. At the synaptic level, while mPFC from VPA animals showed increased synaptophysin (SYN) immunostaining, a SYN deficit was found in all hippocampal subfields. Additionally, both the mPFC and the hippocampus of VPA rats showed increased neuronal cell adhesion molecule (NCAM) immunostaining together with decreased levels of its polysialylated form (PSA-NCAM). Interestingly, these changes were more robust in the CA3 hippocampal subfield. Our results indicate that exploratory and social deficits correlate with region-dependent neuronal disorganization and reactive

  18. Absent activation in medial prefrontal cortex and temporoparietal junction but not superior temporal sulcus during the perception of biological motion in schizophrenia: a functional MRI study

    Directory of Open Access Journals (Sweden)

    Hashimoto N

    2014-11-01

    Full Text Available Naoki Hashimoto,1,2 Atsuhito Toyomaki,1 Masahiro Hirai,3 Tamaki Miyamoto,1 Hisashi Narita,1 Ryo Okubo,1 Ichiro Kusumi1 1Department of Psychiatry, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Child and Adolescent Psychiatry, Department of Psychiatry, University of California, San Francisco, CA, USA; 3Center for Development of Advanced Medical Technology, Jichi Medical University, Yakushiji, Shimotsuke, Tochigi, Japan Background: Patients with schizophrenia show disturbances in both visual perception and social cognition. Perception of biological motion (BM is a higher-level visual process, and is known to be associated with social cognition. BM induces activation in the “social brain network”, including the superior temporal sulcus (STS. Although deficits in the detection of BM and atypical activation in the STS have been reported in patients with schizophrenia, it remains unclear whether other nodes of the “social brain network” are also atypical in patients with schizophrenia.Purpose: We aimed to explore whether brain regions other than STS were involved during BM perception in patients with schizophrenia, using functional magnetic resonance imaging (fMRI.Methods and patients: Seventeen patients with schizophrenia, and 17 age- and sex- matched healthy controls, underwent fMRI scanning during a one-back visual task, containing three experimental conditions: (1 BM, (2 scrambled motion (SM, and (3 static condition. We used one-sample t-tests to examine neural responses selective to BM versus SM within each group, and two-sample t-tests to directly compare neural patterns to BM versus SM in schizophrenics versus controls.Results: We found significant activation in the STS region when BM was contrasted with SM in both groups, with no significant difference between groups. On the contrary, significant activation in the medial prefrontal cortex (MPFC and bilateral temporoparietal junction (TPJ was found only in the

  19. N-acetyl-S-(N,N-diethylcarbamoyl) cysteine in rat nucleus accumbens, medial prefrontal cortex, and in rat and human plasma after disulfiram administration.

    Science.gov (United States)

    Winefield, Robert D; Heemskerk, Anthonius A M; Kaul, Swetha; Williams, Todd D; Caspers, Michael J; Prisinzano, Thomas E; McCance-Katz, Elinore F; Lunte, Craig E; Faiman, Morris D

    2015-03-25

    Disulfiram (DSF), a treatment for alcohol use disorders, has shown some clinical effectiveness in treating addiction to cocaine, nicotine, and pathological gambling. The mechanism of action of DSF for treating these addictions is unclear but it is unlikely to involve the inhibition of liver aldehyde dehydrogenase (ALDH2). DSF is a pro-drug and forms a number of metabolites, one of which is N-acetyl-S-(N,N-diethylcarbamoyl) cysteine (DETC-NAC). Here we describe a LCMS/MS method on a QQQ type instrument to quantify DETC-NAC in plasma and intracellular fluid from mammalian brain. An internal standard, the N,N-di-isopropylcarbamoyl homolog (MIM: 291>128) is easily separable from DETC-NAC (MIM: 263>100) on C18 RP media with a methanol gradient. The method's linear range is 0.5-500 nM from plasma and dialysate salt solution with all precisions better than 10% RSD. DETC-NAC and internal standards were recovered at better than 95% from all matrices, perchloric acid precipitation (plasma) or formic acid addition (salt) and is stable in plasma or salt at low pH for up to 24 h. Stability is observed through three freeze-thaw cycles per day for 7 days. No HPLC peak area matrix effect was greater than 10%. A human plasma sample from a prior analysis for S-(N,N-diethylcarbamoyl) glutathione (CARB) was found to have DETC NAC as well. In other human plasma samples from 62.5 mg/d and 250 mg/d dosing, CARB concentration peaks at 0.3 and 4 nM at 3 h followed by DETC-NAC peaks of 11 and 70 nM 2 h later. Employing microdialysis sampling, DETC-NAC levels in the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and plasma of rats treated with DSF reached 1.1, 2.5 and 80 nM at 6h. The correlation between the appearance and long duration of DETC-NAC concentration in rat brain and the persistence of DSF-induced changes in neurotransmitters observed by Faiman et al. (Neuropharmacology, 2013, 75C, 95-105) is discussed.

  20. [Is the prefrontal cortex the center of the universe?].

    Science.gov (United States)

    Garcia-Molina, A; Ensenat, A

    2015-10-16

    Introduccion. Actualmente, cuando reflexionamos sobre cual es la estructura mas relevante del encefalo humano invariablemente pensamos en las regiones anteriores de la corteza cerebral, concretamente en la corteza prefrontal. Si bien este ha sido el dogma predominante a lo largo de mas de 150 años, investigadores de reconocido prestigio han cuestionado abiertamente tal supuesto. Desarrollo. A caballo entre los siglos XIX y XX, diversos investigadores consideraron que las regiones corticales posteriores son la sede neuroanatomica de las mas altas facultades intelectuales. Entre todos ellos destaco, por la elaboracion de sus propuestas e impacto en la comunidad cientifica, el neuroanatomista aleman Paul Emil Flechsig (1847-1929). Wilder Graves Penfield (1891-1976) fue otro detractor del dogma que considera la corteza prefrontal el sustrato anatomico de los procesos mentales mas complejos y sublimes del ser humano. A mediados del siglo XX, Penfield mantuvo la hipotesis de la existencia de lo que denomino el sistema de integracion centrencefalico, responsable del nivel mas elevado de integracion del sistema nervioso central. Conclusiones. Las concepciones corticocentricas otorgan el preciado cetro de 'estructura mas importante del encefalo' a la corteza prefrontal. Sin embargo, no han faltado propuestas alternativas que, con mayor o menor exito, han intentado arrebatarselo en favor de otras estructuras encefalicas.

  1. Unilateral lesion of the nigrostriatal pathway decreases the response of fast-spiking interneurons in the medial prefrontal cortex to 5-HT1A receptor agonist and expression of the receptor in parvalbumin-positive neurons in the rat.

    Science.gov (United States)

    Gui, Z H; Zhang, Q J; Liu, J; Zhang, L; Ali, U; Hou, C; Fan, L L; Sun, Y N; Wu, Z H; Hui, Y P

    2011-10-01

    5-Hydroxytryptamine(1A) (5-HT(1A)) receptors are expressed in the prefrontal cortical interneurons. Among these interneurons, calcium-binding protein parvalbumin (PV)-positive fast spiking (FS) interneurons play an important role in regulatory function of the prefrontal cortex. In the present study, the response of medial prefrontal cortex (mPFC) FS interneurons to the selective 5-HT(1A) receptor agonist 8-OH-DPAT and change in expression of 5-HT(1A) receptor on PV-positive neurons were examined in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) by using extracellular recording and double-labeling immunofluorescence histochemistry. Systemic administration of 8-OH-DPAT (1-243 μg/kg, i.v.) dose-dependently inhibited the mean firing rate of the FS interneurons in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition in the lesioned rats (243 μg/kg) was significantly higher than that of sham-operated rats (27 μg/kg). Furthermore, the local application of 8-OH-DPAT (0.01 μg) in the mPFC inhibited the FS interneurons in sham-operated rats, while having no effect on firing rate of the FS interneurons in the lesioned rats. In contrast to sham-operated rats, the lesion of the SNc in rats did not cause the change of PV-positive neurons in the prelimbic prefrontal cortex, a subregion of the mPFC, whereas the lesion of the SNc markedly reduced in percentage of PV-positive neurons expressing 5-HT(1A) receptors. Our results indicate that degeneration of the nigrostriatal pathway results in the decreased response of FS interneurons in the mPFC to 5-HT(1A) receptor stimulation, which attributes to down-regulation of 5-HT(1A) receptor expression in these interneurons.

  2. Altered Regulation of Protein Kinase A Activity in the Medial Prefrontal Cortex of Normal and Brain-Injured Animals Actively Engaged in a Working Memory Task

    OpenAIRE

    Kobori, Nobuhide; Moore, Anthony N.; Pramod K Dash

    2015-01-01

    Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) signaling is required for short- and long-term memory. In contrast, enhanced PKA activity has been shown to impair working memory, a prefrontal cortex (PFC)-dependent, transient form of memory critical for cognition and goal-directed behaviors. Working memory can be impaired after traumatic brain injury (TBI) in the absence of overt damage to the PFC. The cellular and molecular mechanisms that contribute to this deficit ar...

  3. GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding.

    Science.gov (United States)

    Baldo, Brian A; Spencer, Robert C; Sadeghian, Ken; Mena, Jesus D

    2016-03-01

    A microanalysis of hunger-driven and palatability-driven feeding was carried out after muscimol-mediated inactivation of two frontal regions in rats, the agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex (vmPFC). Food and water intake, feeding microstructure, and general motor activity were measured under two motivational conditions: food-deprived rats given standard chow or ad libitum-fed rats given a palatable chocolate shake. Muscimol infusions into the AIC diminished intake, total feeding duration, and average feeding bout duration for the palatable-food condition only but failed to alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC muscimol infusions did not alter the overall intake of chow or chocolate shake. However, these infusions markedly increased mean feeding bout duration for both food types and produced a modest but significant reduction of exploratory-like behavior. The lengthening of feeding-bout duration and reduction in rearing were mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate receptors. Neither water consumption nor the microstructure of water drinking was affected by inactivation of either site. These results indicate a regional heterogeneity in frontal control of feeding behavior. Neural processing in AIC supports palatability-driven feeding but is not necessary for intake of a standard food under a food-restriction condition, whereas ventromedial prefrontal cortex, and AMPA signaling therein, modulates the duration of individual feeding bouts regardless of motivational context. Results are discussed in the context of regionally heterogeneous frontal modulation of two distinct components of feeding behavior: reward valuation based upon taste perception (AIC) vs switching between ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires (vmPFC).

  4. Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood.

    Science.gov (United States)

    Burleson, Cody A; Pedersen, Robert W; Seddighi, Sahba; DeBusk, Lauren E; Burghardt, Gordon M; Cooper, Matthew A

    2016-08-01

    Social play is a fundamental aspect of behavioral development in many species. Social play deprivation in rats alters dendritic morphology in the ventromedial prefrontal cortex (vmPFC) and we have shown that this brain region regulates responses to social defeat stress in Syrian hamsters. In this study, we tested whether play deprivation during the juvenile period disrupts dendritic morphology in the prefrontal cortex and potentiates the effects of social defeat stress. At weaning, male hamsters were either group-housed with peers or pair-housed with their mother, with whom they do not play. In adulthood, animals received acute social defeat stress or no-defeat control treatment. The hamsters were then tested for a conditioned defeat response in a social interaction test with a novel intruder, and were also tested for social avoidance of a familiar opponent. Brains were collected for Golgi-Cox staining and analysis of dendritic morphology in the infralimbic (IL), prelimbic (PL), and orbitofrontal cortex (OFC). Play-deprived animals showed an increased conditioned defeat response and elevated avoidance of a familiar opponent compared with play-exposed animals. Furthermore, play-deprived animals showed increased total length and branch points in apical dendrites of pyramidal neurons in the IL and PL cortices, but not in the OFC. These findings suggest that social play deprivation in juvenile hamsters disrupts neuronal development in the vmPFC and increases vulnerability to the effects of social stress in adulthood. Overall, these results suggest that social play is necessary for the natural dendritic pruning process during adolescence and promotes coping with stress in adulthood. (PsycINFO Database Record

  5. Change in expression of mineralocorticoid receptors in medial prefrontal cortex of rats with posttraumatic stress disorder%创伤后应激障碍大鼠前额内侧皮质MR表达的变化

    Institute of Scientific and Technical Information of China (English)

    张景华; 李慢; 石玉秀; 韩芳

    2011-01-01

    Objective To observe the expression of mineralocorticoid receptors (MR) in the medial prefrontal cortex (mPFC) of rats with posttraumatic stress disorder (PTSD) . Methods The single prolonged stress (SPS) method was used to set up the rat PTSD models. A total of 90 male Wistar rats were randomly divided into 1d, 7d, 14d, 28d of SPS groups and normal control group. Immunohistochemistry,Western blotting, RTPCR, image analysis and statistical analysis were used to detect the activity of MR.Results The activity of MR in mPFC neurons increased at ld after exposure to SPS compared with that of the control group, then gradually decreased, reached the minimum at 14d, and restored t0 28d, but still lower than that of the control group (P<0. 05). Conclusion The expression of MR may be related to the pathogenesis of HPA.%目的 观察创伤后应激障碍(PTSD)样大鼠前额内侧皮质(medial prefrontal cortex, mPFC)神经元核受体-盐皮质激素受体(Mineralocorticoid receptors,MR)表达的变化.方法 采用国际认定的单一连续应激(single prolonged stress, SPS)方法建立PTSD大鼠模型,取成年健康雄性Wistar大鼠90只,随机分为PTSD模型1d、7d、14d、28d和正常对照组.采用免疫组化、免疫印迹和RT-PCR方法分别进行各组mPFC神经元MR表达变化的观察及检测,进行图像分析和统计学处理.结果 PTSD大鼠mPFC神经元MR的表达在SPS-1d时高于对照组,随后下降,SPS-14d最低,SPS-28d恢复性上调,但仍然低于对照组(P<0.05).结论 PTSD模型大鼠经SPS处理后,mPFC中出现MR表达的变化,该变化可能参与PTSD的下丘脑-垂体-肾上腺(hypothalamic pituitary adren axis,HPA)轴的变化机制.

  6. [Effect of synchronous perfusion of NaN3 in changes in content of cholinergic neurotransmitter in medial prefrontal cortex and hippocampal extra-cellular fluid].

    Science.gov (United States)

    Zhang, Mei-Yu; Sun, Dan-Dan; Liu, Yang; Cui, Yue; Zhao, Xiao-Liang; Zhang, Ying; Wang, Zhi-Guo; Wang, Dan-Qiao

    2014-02-01

    To observe the effect of synchronous perfusion of specific respiratory chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in hippocampal extra-cellular fluid, and establish the AD rat model induced by mitochondrial acute injury. The synchronous dual-probe dual-channel brain microdialysis sampling technology was applied to synchronously perfuse modified Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and continuously collect dialysates from different encephalic areas. Dynamic contents of ACh and Ch were determined by high performance liquid chromatography-post-column immobilized enzyme reactor-electrochemical process. ACh and Ch contents in mPFC extracellular fluid of normal rats were higher than that in hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus. The synchronous perfusion of NaN3in rat mPFC and hippocampus can injure functions of the cholinergic nerve projection area, and cause the acute AD model with ACh and Ch metabolic disorders. This model can be used in pathogenetic and pharmacological studies.

  7. Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial.

    Science.gov (United States)

    Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

    2015-04-01

    The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.

  8. The Abused Inhalant Toluene Differentially Modulates Excitatory and Inhibitory Synaptic Transmission in Deep-Layer Neurons of the Medial Prefrontal Cortex

    Science.gov (United States)

    Beckley, Jacob T; Woodward, John J

    2011-01-01

    Volatile organic solvents such as toluene are voluntarily inhaled for their intoxicating effects. Solvent use is especially prevalent among adolescents, and is associated with deficits in a wide range of cognitive tasks including attention, behavioral control, and risk assessment. Despite these findings, little is known about the effects of toluene on brain areas mediating these behaviors. In this study, whole-cell patch-clamp recordings were used to determine the effect toluene on neurons within the medial PFC, a region critically involved in cognitive function. Toluene had no effect on measures of intrinsic excitability, but enhanced stimulus-evoked γ-amino butyric acid A-mediated inhibitory postsynaptic currents (IPSCs). In the presence of tetrodotoxin (TTX) to block action potentials, toluene increased the frequency and amplitude of miniature IPSCs. In contrast, toluene induced a delayed but persistent decrease in evoked or spontaneous AMPA-mediated excitatory postsynaptic currents (EPSCs). This effect was prevented by an intracellular calcium chelator or by the ryanodine receptor and SERCA inhibitors, dantrolene or thapsigargin, respectively, suggesting that toluene may mobilize intracellular calcium pools. The toluene-induced reduction in AMPA EPSCs was also prevented by a cannabinoid receptor (CB1R) antagonist, and was occluded by the CB1 agonist WIN 55,212-2 that itself induced a profound decrease in AMPA-mediated EPSCs. Toluene had no effect on the frequency or amplitude of miniature EPSCs recorded in the presence of TTX. Finally, toluene dose-dependently inhibited N-methyl--aspartate (NMDA)-mediated EPSCs and the magnitude and reversibility of this effect was CB1R sensitive indicating both direct and indirect actions of toluene on NMDA-mediated responses. Together, these results suggest that the effect of toluene on cognitive behaviors may result from its action on inhibitory and excitatory synaptic transmission of PFC neurons. PMID:21430649

  9. Amigdala, corteza prefrontal y especializacion hemisferica en la experiencia y expresion emocional

    OpenAIRE

    2004-01-01

    Los datos provenientes de la neurociencia señalan a varias estructuras, tanto subcorticales como corticales, relacionadas con la conducta emocional. Tanto los datos derivados de la investigación con sujetos normales como los procedentes de estudios que han empleado pacientes con daño cerebral y técnicas de neuroimagen funcional en sujetos normales, señalan a la amígdala como una estructura fundamental en la emoción, particularmente en la respuesta a estímulos d...

  10. Resting-state Functional Connectivity of Medial Prefrontal Cortex in the Active Opiates User%海洛因成瘾者前额叶内侧皮质的静息状态功能连接

    Institute of Scientific and Technical Information of China (English)

    刘海洪; 阎媛; 张会然; 郝以辉; 刘哲宁

    2013-01-01

    目的:探讨海洛因成瘾者脑默认网络静息状态功能连接的异常.方法:对正在接受美沙酮维持治疗的15例海洛因依赖者和15例健康对照进行静息状态脑功能磁共振扫描,以独立成分分析法获取每一个体的默认网络,并比较两组默认网络的功能连接差异.结果:与健康对照相比,海洛因成瘾者双侧前额叶内侧皮质、左侧颞中回和颞下回、小脑的功能连接升高.结论:前额叶内侧皮质可能是物质成瘾的关键脑区,可为成瘾的生物学诊断和靶向治疗提供线索.%Objective:To investigate the effects of active opiates use on the resting-state functional connectivity of the default network.Methods:Resting-state functional images were obtained from 15 heroin-dependent subjects on methadone maintenance therapy and 15 healthy controls matched for sex,age and education years.Individual's default network was obtained by independent component analysis,and the default network difference between the two groups was explored by two sample t test.Results:Compared with the healthy controls,active opiates user showed increased restingstate functional connectivity in bilateral medial prefrontal cortex (MPFC),left middle and inferior temporal gyrus and cerebellum.Conclusion:The MPFC may be a crucial area of substance addiction.This findings provides cues for the biological diagnosis and region-targeted therapy of addiction.

  11. Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System.

    Science.gov (United States)

    Edemann-Callesen, Henriette; Voget, Mareike; Empl, Laura; Vogel, Martin; Wieske, Franziska; Rummel, Julia; Heinz, Andreas; Mathé, Aleksander A; Hadar, Ravit; Winter, Christine

    2015-01-01

    In recent years, deep brain stimulation (DBS) has emerged as a promising treatment option for patients suffering from treatment-resistant depression (TRD). Several stimulation targets have successfully been tested in clinical settings, including the subgenual cingulum (Cg25) and the medial forebrain bundle (MFB). MFB-DBS has led to remarkable results, surpassing the effect of previous targets in terms of response latency and number of responders. However, the question remains as to which mechanisms underlie this difference. The aim of the present study was to thoroughly study the anti-depressant effect of MFB-DBS in the Flinders sensitive line (FSL) rat model of depression as well as to investigate whether MFB-DBS and Cg25-DBS operate through the same neurobiological circuits. FSL and control rats received bilateral high-frequency stimulation to the MFB at the level of the lateral hypothalamus, while being subjected to a variety of depression- and anxiety-related behavioral paradigms. To further compare the effects of MFB-DBS and Cg25-DBS on reward-related behavior, animals were stimulated in either the MFB or ventromedial prefrontal cortex (vmPFC, rodent analog to Cg25), while being tested in the intra-cranial self-stimulation paradigm. A marked symptom-specific anti-depressant effect of MFB-DBS was demonstrated. The ICSS-paradigm revealed that MFB-DBS, as opposed to vmPFC-DBS interacts with the reward system. Our data suggest that MFB-DBS and Cg25-DBS do not operate via the same neurobiological circuits. This differentiation might be of interest when selecting patients for either Cg25- or MFB-DBS. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex.

    Science.gov (United States)

    Schindler, Emmanuelle A D; Harvey, John A; Aloyo, Vincent J

    2013-01-23

    The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct pharmacological properties, although they share a serotonin(2A) (5-HT(2A)) receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens remains unclear. In order to better understand the role of PI hydrolysis in the MOA of hallucinogens, the PLC inhibitor, 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to study the effects of two hallucinogens, the phenethylamine, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the indoleamine, lysergic acid diethylamide (LSD). PI hydrolysis was quantified through release of [3H]inositol-4-phosphate from living rabbit frontocortical tissue prisms. Head bobs were counted after hallucinogens were infused into the medial prefrontal cortex (mPFC) of rabbits. Both DOI and LSD stimulated PI hydrolysis in frontocortical tissue through activation of PLC. DOI-stimulated PI hydrolysis was blocked by 5-HT(2A/2C) receptor antagonist, ketanserin, whereas the LSD signal was blocked by 5-HT(2B/2C) receptor antagonist, SB206553. When infused into the mPFC, both DOI- and LSD-elicited head bobs. Pretreatment with U73122 blocked DOI-, but not LSD-elicited head bobs. The two hallucinogens investigated were distinct in their activation of the PI hydrolysis signaling pathway. The serotonergic receptors involved with DOI and LSD signals in frontocortical tissue were different. Furthermore, PLC activation in mPFC was necessary for DOI-elicited head bobs, whereas LSD-elicited head bobs were independent of this pathway. These novel findings urge closer investigation into the intracellular mechanism of action of these unique compounds. Published by Elsevier B.V.

  13. Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

    Directory of Open Access Journals (Sweden)

    Daniel Scott Schechter

    2015-05-01

    Full Text Available Prior research has shown that mothers with Interpersonal Violence-related Posttraumatic Stress Disorder (IPV-PTSD report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis, characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress

  14. Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning.

    Science.gov (United States)

    Lin, P-Y; Wang, S-P; Tai, M-Y; Tsai, Y-F

    2010-11-24

    Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is

  15. Importancia de considerar corteza no-homogénea en sismología

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    Isabel Restrepo

    2003-01-01

    Full Text Available La corteza terrestre no es una masa uniforme y homogénea. Es una sucesión de rocas que poseen distinto origen y naturaleza, de allí que se distingan en cuanto a sus propiedades mecánicoestructurales y que se comporten de una manera particular cuando viaja a través de ellas una onda sísmica. Se plantea un análisis geofísico del sismo del 25 de enero de 1999, en el Eje Cafetero Colombiano, que incluye la cuantificación de velocidades de propagación de la onda P en corteza no homogénea y las comparaciones con los resultados obtenidos en corteza homogénea.

  16. Aislamiento de poligodial de la corteza de drymis granadensis, var. grandiflora

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    Jairo Calle

    2009-07-01

    Full Text Available Del extracto de éter de petróleo (P Eb = 40-60 "O de la corteza de Drymis granadensis, var. grandiflora, se aisló con 8% de rendimiento, poligodial ( I , un sesquiterpeno conocido, cuya estructura se confirmó por métodos espectroscópicos.

  17. 额前皮质内侧区和眶回损伤后恐惧情绪管理改变的初步分析%Initial analysis of changes in fear mangement after circumscribed injury of orbitofrontal cortex and medial region of prefrontal cortex

    Institute of Scientific and Technical Information of China (English)

    余新光; 周岩; 许燕

    2010-01-01

    Objective To initially analyze the changes in fear management and neural network after circumscribed injury of the orbitofrontal cortex and medial region of prefrontal cortex. Method The correlation analysis between MRI features and psychological tests was performed in 7 cases with injury of orbitofrontal cortex and/or medial region of prefrontal cortex. The control group included 5 patients with mild brain trauma and without abnormal feature on MRI. Results Patients with injury of orbitofrontal cortex and/ or the medial region of prefrontal cortex showed obvious extinction on emotion control and fear emotion for death, obvious antisocial personality, enhancement of aggression, and depression, in which two patients with circumscribed injury of orbitofrontal cortex showed predominant changes in fear management. The control group was normal in fear management Conclusions Impairments of orbitofrontal cortex and medial region of prefrontal cortex may disrupt the evaluation of fear.%目的 探讨额前皮质内侧区和眶回局限性损伤后恐惧情绪控制的变化模式及其神经结构基础.方法 对7例额前皮质内侧区和眶回损伤的病例进行MRI影像和心理测评比对分析,并进行统计描述.对照组为5例MRI影像正常的轻度颅脑创伤患者.结果 所有7例额前皮质内侧区和眶回损伤后患者均表现有情绪控制力下降,明显的反社会人格,对死亡的恐惧几近下降,攻击性显著增强,尤以2例眶回局限性损伤的患者表现突出.对照组中所有病例的情感等高级认知功能均正常,无反社会人格表现,恐惧管理表现正常,图片知觉整合能力正常,自我控制能力正常,无恐惧情绪控制异常.结论 额前皮质内侧区和眶回负责恐惧信息的评价,该部位损伤后可导致异常的主观情感状态和社会行为,因而额前皮质内侧区和眶回可能与恐惧信息的评价有关.

  18. Un acercamiento a las cortezas de meteorización no niquelíferas del nordeste de Cuba

    Directory of Open Access Journals (Sweden)

    Arturo L. Rojas-Purón

    2010-03-01

    Full Text Available Este artículo expone el resultado de la revisión de los estudios sobre cortezas de meteorización no niquelíferas realizados en Cuba Oriental a partir de 1943, los cuales estuvieron dirigidos a la búsqueda de bauxitas, motivados por la existencia en la región de grandes depósitos minerales asociados a diferentes tipos de cortezas de meteorización. Los bajos contenidos de alúmina reportados no permitieron delimitar cortezas perspectivas para la explotación de bauxitas, lo que limitó la evaluación de las posibilidades de asimilar estas cortezas en industrias nacionales como la cerámica, materiales de construcción y refractaria, entre otras. Como elemento común de estos estudios vale señalar la ausencia, casi general, de criterios mineralógicos-geoquímicos sólidos para la caracterización y clasificación de las distintas cortezas de meteorización enriquecidas en alúmina. Los contenidos de SiO2-Al2O3-Fe2O3 en la región apuntan a que la mayoría de las cortezas de meteorización son ferrosialíticas. Cortezas sialíticas, silícicas, ferralíticas y alíticas pueden encontrarse en Cayo Guam, Centeno, Quesigua, Puriales de Caujerí, Quemado del Negro y Cantarrana. El grado de estudio de las cortezas de meteorización no niquelíferas sobre gabros, rocas volcánicas, metamórficas y sedimentarias, en Cuba Oriental es relativamente bajo. Se proponen realizar investigaciones detalladas en Téneme, Centeno, Cayo Guam, Quemado del Negro y Cantarrana con perspectivas para alitas.

  19. Cortezas de Prosopis laevigata (Fabaceae) y Schinus molle (Anacardiaceae) como bioindicadoras de contaminación por metales pesados

    OpenAIRE

    Alcalá Jáuregui, Jorge; Rodríguez Ortíz, Juan C.; Hernández Montoya, Alejandra; Díaz Flores, Paola Elisabeth; Filippini, María Flavia; Martínez Carretero, Eduardo

    2015-01-01

    La corteza arbórea constituye un elemento viable para diagnosticar la contaminación por metales pesados. Fue evaluada la presencia de once metales pesados en corteza de P. laevigata "mezquite" y S. molle "pirul" como indicador de impacto ambiental en San Luis Potosí, México. Basado en la presencia de estas dos especies sobre un sistema fragmentado por usos de suelo agropecuario, asentamiento rural, comercial y servicio, asentamiento urbano y minero, se tomó muest...

  20. Lignano Furofuránicos en Corteza de Virola Sebífera (Aublet

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    Luis E. Cuca S.

    2009-07-01

    Full Text Available Del extracto toluénico de la corteza de Virola sebífera (Myristicaceae, se aislaron e identificaron dos lignanos furofuránicos (3,7-dioxabiciclo (3,3,0 octánicos, que correspondieron a la ( + -sesamina y ( + -kobusina. Las elucidaciones estructurales fueron realizadas por métodos espectroscópicos en correlación con datos de la  literatura.

  1. Actividad del hipocampo y la corteza motora primaria durante el aprendizaje motor

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    José María Delgado García

    2005-03-01

    Full Text Available El condicionamiento clásico del parpadeo y de la protracción de las vibrisas ha sido utilizado para estudiar los mecanismos neuronales que subyacen al aprendizaje motor.  Se han identificado diversas estructuras que participan en este proceso, pero aún se discute cuál es el papel desempeñado por el hipocampo y la corteza motora primaria.

  2. Constituyentes no polares de la corteza de esenbeckia ahita y actividad antimicrobiana

    Directory of Open Access Journals (Sweden)

    Olimpo García Beltrán

    2010-10-01

    Full Text Available De la corteza de Esenbeckia alata (Rutaceae se aislaron cuatro compuestos identificados como: 5-hidroxi-2-metilcromanona aislado por primera vez en vegetales (en este trabajo se completan sus datos espectroscópicos, (--episesamina, la amida pellitonina y sitosterol. La elucidación estructural de estos compuestos se realizó mediante técnicas espectroscópicas (IR. UV. RMN 1H y 13C y EM.

  3. Altered dendritic distribution of dopamine D2 receptors and reduction in mitochondrial number in parvalbumin-containing interneurons in the medial prefrontal cortex of cannabinoid-1 (CB1) receptor knockout mice

    OpenAIRE

    2012-01-01

    The prelimbic prefrontal cortex (PL) is a brain region integral to complex behaviors that are highly influenced by cannabinoids and by dopamine D2 receptor (D2R)-mediated regulation of fast-firing parvalbumin-containing interneurons. We have recently shown that constitutive deletion of the cannabinoid CB1 receptor (CB1R) greatly reduces parvalbumin levels in these neurons. The effects of CB1R deletion on PL parvalbumin interneurons may be ascribed to loss of CB1R-mediated retrograde signaling...

  4. vInterocepción y corteza insular: convergencia multimodal y surgimiento de la conciencia corporal

    OpenAIRE

    Juan Blas Couto; Lucas Sedeño; Agustín Ibáñez

    2012-01-01

    La interocepción como censado del estado homeostático y visceral, ha sido recientemente postulada como requisito para la conciencia de estados emocionales corporales (Craig, 2009). Vías parasimpáticas y espinotalámicas que codifican esta información corporal tienen relevo en la corteza insular. Simultáneamente, han sido descriptas otras funciones insulares implicadas en procesos conscientes, como la intencionalidad, la toma de decisiones, la conciencia sensorio-motora, la percepción temporal,...

  5. Altered dendritic distribution of dopamine D2 receptors and reduction in mitochondrial number in parvalbumin-containing interneurons in the medial prefrontal cortex of cannabinoid-1 (CB1) receptor knockout mice.

    Science.gov (United States)

    Fitzgerald, Megan L; Chan, June; Mackie, Kenneth; Lupica, Carl R; Pickel, Virginia M

    2012-12-01

    The prelimbic prefrontal cortex (PL) is a brain region integral to complex behaviors that are highly influenced by cannabinoids and by dopamine D2 receptor (D2R)-mediated regulation of fast-firing parvalbumin-containing interneurons. We have recently shown that constitutive deletion of the cannabinoid-1 receptor (CB1R) greatly reduces parvalbumin levels in these neurons. The effects of CB1R deletion on PL parvalbumin interneurons may be ascribed to loss of CB1R-mediated retrograde signaling on mesocortical dopamine transmission, and, in turn, altered expression and/or subcellular distribution of D2R in the PL. Furthermore, diminished parvalbumin expression could indicate metabolic changes in fast-firing interneurons that may be reflected in changes in mitochondrial density in this population. We therefore comparatively examined electron microscopic dual labeling of D2R and parvalbumin in CB1 (-/-) and CB1 (+/+) mice to test the hypothesis that absence of CB1R produces changes in D2R localization and mitochondrial distribution in parvalbumin-containing interneurons of the PL. CB1 (-/-) mice had a significantly lower density of cytoplasmic D2R-immunogold particles in medium parvalbumin-labeled dendrites and a concomitant increase in the density of these particles in small dendrites. These dendrites received both excitatory and inhibitory-type synapses from unlabeled terminals and contained many mitochondria, whose numbers were significantly reduced in CB1 (-/-) mice. Non-parvalbumin dendrites showed no between-group differences in either D2R distribution or mitochondrial number. These results suggest that cannabinoid signaling provides an important determinant of dendritic D2 receptor distribution and mitochondrial availability in fast-spiking interneurons.

  6. Influencias nutricionales sobre las capacidades gluconeogénica y glucolítica de corteza renal de rata

    OpenAIRE

    García Salguero, Leticia.

    2013-01-01

    Se ha puesto de manifiesto la importancia de la corteza renal en el mantenimiento de los niveles de glucosa sanguínea. El riñón es capaz de adaptar el metabolismo de carbohidratos ante diferentes situaciones nutricionales. Así cuando hay un aporte excesivo de carbohidratos en la dieta el riñón responde disminuyendo la gluconeogénesis e incrementando la glucólisis igual que ocurre en el hígado. En el ayuno los cambios que tienen lugar en la corteza renal siguen una dirección opuesta

  7. Estudio fitoquímico de la corteza de acacia farnesianautilizada tradicionalmente para el tratamiento de la malaria

    OpenAIRE

    Daza Bareño, Ada Zurima

    2014-01-01

    En Colombia se ha reportado el uso de decocciones de las hojas y la corteza de Acacia farnesiana para el tratamiento de fiebres y malaria. El presente trabajo es una contribución al estudio fitoquímico de la corteza de esta especie colectada en dos épocas del año, época seca (junio) y de lluvia (octubre). Para tal fin se recolectó el material vegetal en Armero-Guayabal, Departamento Tolima (Colombia) y se realizó una caracterización fitoquímica del extracto etanólico obtenido por percolación ...

  8. Influencias nutricionales sobre las capacidades gluconeogénica y glucolítica de corteza renal de rata

    OpenAIRE

    García Salguero, Leticia

    2013-01-01

    Se ha puesto de manifiesto la importancia de la corteza renal en el mantenimiento de los niveles de glucosa sanguínea. El riñón es capaz de adaptar el metabolismo de carbohidratos ante diferentes situaciones nutricionales. Así cuando hay un aporte excesivo de carbohidratos en la dieta el riñón responde disminuyendo la gluconeogénesis e incrementando la glucólisis igual que ocurre en el hígado. En el ayuno los cambios que tienen lugar en la corteza renal siguen una dirección opuesta

  9. Complementary Patterns of Direct Amygdala and Hippocampal Projections to the Macaque Prefrontal Cortex.

    Science.gov (United States)

    Aggleton, John P; Wright, Nicholas F; Rosene, Douglas L; Saunders, Richard C

    2015-11-01

    The projections from the amygdala and hippocampus (including subiculum and presubiculum) to prefrontal cortex were compared using anterograde tracers injected into macaque monkeys (Macaca fascicularis, Macaca mulatta). Almost all prefrontal areas were found to receive some amygdala inputs. These connections, which predominantly arose from the intermediate and magnocellular basal nucleus, were particularly dense in parts of the medial and orbital prefrontal cortex. Contralateral inputs were not, however, observed. The hippocampal projections to prefrontal areas were far more restricted, being confined to the ipsilateral medial and orbital prefrontal cortex (within areas 11, 13, 14, 24a, 32, and 25). These hippocampal projections principally arose from the subiculum, with the fornix providing the sole route. Thus, while the lateral prefrontal cortex essentially receives only amygdala inputs, the orbital prefrontal cortex receives both amygdala and hippocampal inputs, though these typically target different areas. Only in medial prefrontal cortex do direct inputs from both structures terminate in common sites. But, even when convergence occurs within an area, the projections predominantly terminate in different lamina (hippocampal inputs to layer III and amygdala inputs to layers I, II, and VI). The resulting segregation of prefrontal inputs could enable the parallel processing of different information types in prefrontal cortex.

  10. Aporfinoides en corteza de guntteriu lehmannii y evaluación de su actividad antimalárica in vitro

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    Alex Saez

    2010-07-01

    Full Text Available Un extracto de alcaloides de la corteza de Guatteria lehmannii presentó actividad antimalárica in vitro, se aislaron tres alcaloides aporfínicos. Nornuciferína 1, Lysicamína 2 y Norneolilsína 3.. Las estructuras se determinaron por métodos espectrales.

  11. [Prefrontal cortex in memory and attention processes].

    Science.gov (United States)

    Allegri, R F; Harris, P

    The role of the prefrontal cortex still remains poorly understood. Only after 1970, the functions of the frontal lobes have been conceptualized from different points of view (behaviorism, cognitivism). Recently,different parallel circuits connecting discrete cortical and subcortical regions of the frontal lobes have been described. Three of these circuits are the most relevant to understanding of behavior: the dorsolateral prefrontal circuit, that mediates executive behavior; the orbitofrontal prefrontal circuit, mediating social behavior, and the medial frontal circuit, involved in motivation. Damage to the frontal cortex impairs planning, problem solving, reasoning, concept formation, temporal ordering of stimuli, estimation, attention, memory search, maintaining information in working memory, associative learning,certain forms of skilled motor activities, image generation and manipulation of the spatial properties of a stimulus, metacognitive thinking, and social cognition. Several theories have been proposed to explain the functions of the prefrontal cortex. Currently,the most influential cognitive models are: the Norman and Shallice supervisory attentional system, involved in non-routine selection; the Baddeley working memory model with the central executive as a supervisory controlling system, in which impairment leads to a 'dysexecutive syndrome'; and the Grafman's model of managerial knowledge units, stored as macrostructured information in the frontal cortex. The prefrontal cortex is essential for attentional control, manipulation of stored knowledge and modulation of complex actions, cognition, emotion and behavior.

  12. ESTUDIO QUÍMICO DE LA CORTEZA DE Remijia peruviana “Cascarilla”

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    Gabriel Vargas Arana

    2011-07-01

    Full Text Available En el presente trabajo se realizó el análisis cualitativo de los metabolitos secundarios  y la cuantificación e identificación de los alcaloides presentes en la corteza de Remijia peruviana, la cual forma parte de la familia Rubiaceae, caracterizada por sintetizar  mayoritariamente alcaloides. Se ha aislado y determinado la estructura química de cinco alcaloides quinolínicos: tres nuevos derivados, Quinina acetato (1, Quinina alcohol (2 y N-Etil Quinina (3; y dos reportados anteriormente en la literatura: Quinina (4 y Cinchonina (5. La estructura de los nuevos alcaloides fueron elucidados por análisis básicos de espectroscopía RMN, incluyendo correlaciones homonuclear y heteronuclear (COSY, NOESY, HMBC y HSQC.

  13. CONSTITUYENTES NO POLARES DE LA CORTEZA DE Esenbeckia alata Y ACTIVIDAD ANTIMICROBIANA

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    Olimpo García Beltrán

    2008-02-01

    Full Text Available De la corteza de Esenbeckia alata (Rutaceae se aislaron cuatro compuestos identificados como: 5-hidroxi-2-metilcromanonaaislado por primera vez en vegetales (en este trabajo se completan sus datos espectroscópicos, (--episesamina,la amida pellitonina y sitosterol.La elucidación estructural de estos compuestos se realizó mediante técnicas espectroscópicas (IR, UV, RMN 1H y 13C y EM.Se evaluó la actividad antimicrobiana del extracto de éter de petróleo de E. alata, de algunas fracciones de ésta, y del lignano obtenido, presentando resultados significativos frente algunas cepas bacterianas Gram positivas y Gram negativas.

  14. Social cognition in patients following surgery to the prefrontal cortex

    NARCIS (Netherlands)

    Jenkins, L.M.; Andrewes, D.G.; Nicholas, C.L.; Drummond, K.J.; Moffat, B.A.; Phal, P.; Desmond, P.; Kessels, R.P.C.

    2014-01-01

    Impaired social cognition, including emotion recognition, may explain dysfunctional emotional and social behaviour in patients with lesions to the ventromedial prefrontal cortex (VMPFC). However, the VMPFC is a large, poorly defined area that can be sub-divided into orbital and medial sectors. We

  15. Anatomía funcional del cuerpo estriado y la corteza cerebral: su relación con el movimiento

    OpenAIRE

    Buffone, Gabriel Darío; Dalto, Carlos

    2013-01-01

    El objetivo de la siguiente ponencia es revalorizar y reconocer aquellos aspectos anatómicos y funcionales de algunos elementos del sistema nervioso imprescindibles para el correcto funcionamiento del cuerpo humano, tanto en los movimientos deportivos, como en la variedad infinita de los actos motores resumidos en las contracciones musculares. Ante los diferentes rangos articulares posibles y las determinadas acciones musculares específicas, la corteza cerebral y el cuerpo estriado partici...

  16. PODER CALORÍFICO Y MATERIAL INORGÁNICO EN LA CORTEZA DE SEIS ÁRBOLES FRUTALES

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    Ricardo Martínez-Pérez

    2012-01-01

    Full Text Available El poder calorífico y el contenido de sustancias minerales (cenizas se determinaron en la corteza de seis especies arbóreas frutales (Annona cherimola Mill., Citrus aurantifolia Swingle, Malus domestica Borkh., Psidium guajava L., Prunus dulcis [Mill.] D. A. Webb y Tamarindus indica L.. Las cenizas obtenidas fueron analizadas mediante rayos X. Los valores encontrados de poder calorífico variaron de 3,453.49 kcal•kg-1 en T. indica a 4,076.10 kcal•kg-1 en P. guajava. En el caso de las cenizas, los resultados fluctuaron de 5.76 % en P. guajava a 21.93 % en T. indica. Se observó que un contenido mayor de minerales en las cortezas tiende a disminuir su poder calorífico. Los elementos químicos comunes en las muestras analizadas fueron calcio, potasio, magnesio, fósforo y azufre. No se detectaron metales pesados en las muestras de la corteza.

  17. Specialized prefrontal auditory fields: organization of primate prefrontal-temporal pathways

    Directory of Open Access Journals (Sweden)

    Maria eMedalla

    2014-04-01

    Full Text Available No other modality is more frequently represented in the prefrontal cortex than the auditory, but the role of auditory information in prefrontal functions is not well understood. Pathways from auditory association cortices reach distinct sites in the lateral, orbital, and medial surfaces of the prefrontal cortex in rhesus monkeys. Among prefrontal areas, frontopolar area 10 has the densest interconnections with auditory association areas, spanning a large antero-posterior extent of the superior temporal gyrus from the temporal pole to auditory parabelt and belt regions. Moreover, auditory pathways make up the largest component of the extrinsic connections of area 10, suggesting a special relationship with the auditory modality. Here we review anatomic evidence showing that frontopolar area 10 is indeed the main frontal auditory field as the major recipient of auditory input in the frontal lobe and chief source of output to auditory cortices. Area 10 is thought to be the functional node for the most complex cognitive tasks of multitasking and keeping track of information for future decisions. These patterns suggest that the auditory association links of area 10 are critical for complex cognition. The first part of this review focuses on the organization of prefrontal-auditory pathways at the level of the system and the synapse, with a particular emphasis on area 10. Then we explore ideas on how the elusive role of area 10 in complex cognition may be related to the specialized relationship with auditory association cortices.

  18. METABOLITOS SECUNDARIOS AISLADOS DE LA CORTEZA DE Dugandiodendron argyrotrichum Lozano (MAGNOLIACEAE

    Directory of Open Access Journals (Sweden)

    Juan Guzmán

    2009-04-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 st1\\:*{behavior:url(#ieooui }   A partir del extracto etanólico de la corteza del árbol colombiano en peligro de extinción Dugandiodendron argyrotrichum (Magnoliaceae se aisló por cromatografía en columna un aceite compuesto mayoritariamente por sesquiterpenos, así como dos sesquiterpenoides, torreyol y partenólido, y  el alcaloide aporfínico N-acetilanonaína, por cromatografía en columna. Los compuestos se identificaron por cromatografía de gases acoplada a espectrometría de masas CG-MS y resonancia magnética nuclear (RMN de 1H y 13C. Los sustancias aisladas se sometieron al ensayo de letalidad en Artemia salina. Aquellos que resultaron más tóxicos fueron el aceite de sesquiterpenos (CL50 = 4.49 μg/ml y los lignanos dibencilbutánicos (1 (CL50 ~ 50 μg/ml.

  19. Distribución de Alcaloides en la Corteza de Algunas Cinchonas Peruanas

    Directory of Open Access Journals (Sweden)

    Hodge W. H.

    1946-08-01

    Full Text Available Los análisis de las muestras seleccionadas de corteza de quinas silvestres que crecían,en el Perú indican que el contenido en alcaloides varía apreciablemente según la posición de la base a los puntos más altos del árbol. En algunos tipos de cinchonas los alcaloides se encuentran en mayor cantidad en la base del tronco que en las partes más altas del árbol pero, en otros tipos de cinchona ocurre lo inverso. Por lo tanto para determinar el rendimiento comercial deben tomarse muestras de estas dos partes del árbol. También aparece cierta relación entre la cantidad de alcaloides presentes en un árbol y su circunferencia (o edad. La cantidad de alcaloides aumenta o disminuye según aumente o disminuya el diámetro y dicha relación depende del alcaloide y del tipo de cinchona.

  20. Modelo gravimétrico del espesor de la corteza terrestre en Colombia

    Directory of Open Access Journals (Sweden)

    Leuro Parra Erick

    2000-08-01

    Full Text Available

    The gravimetric model of the crustal thickness of the earth in Colombia was made from Total Bouguer Anomaly and topographic height given by the Instituto Geográfico Agustín Codazzi. They were transformed to bidimensional series of Fourier, that combined with mathematics expressions of the gravitational potential, both, they made possible to find the crustal thickness starting from observable values across the earth's surface (gravity and topography. The results of several points were converted to surface through Minime Curvature algorithm. In order to obtain reliability of the results, seismic control was applied from another works.

    La determinación del espesor de la corteza terrestre en Colombia, a partir de datos gravimétricos, se hizo utilizando datos de Anomalia Total de Bouguer y altura topográfica suministrados por el Instituto Geográfico Agustin Codazzi. Estos fueron representados mediante series bidimensionales de Fourier, que al ser combinadas con expresiones matemáticas del potencial gravitacional terrestre, permitieron plantear el grosor cortical en términos observables (gravedad y altura sobre la superficie terrestre. Los resultados han sido dispuestos en una malla de puntos que se interpolan a una superficie utilizando el algoritmo de mínima curvatura. Para la estimación de la confiabilidad de los resultados se ha realizado una confrontación con las deducciones geológicas obtenidas de algunas interpretaciones sismicas realizadas en el pais.

  1. Dissociable contributions of the prefrontal cortex to hippocampus- and caudate nucleus-dependent virtual navigation strategies.

    Science.gov (United States)

    Dahmani, Louisa; Bohbot, Véronique D

    2015-01-01

    The hippocampus and the caudate nucleus are critical to spatial- and stimulus-response-based navigation strategies, respectively. The hippocampus and caudate nucleus are also known to be anatomically connected to various areas of the prefrontal cortex. However, little is known about the involvement of the prefrontal cortex in these processes. In the current study, we sought to identify the prefrontal areas involved in spatial and response learning. We used functional magnetic resonance imaging (fMRI) and voxel-based morphometry to compare the neural activity and grey matter density of spatial and response strategy users. Twenty-three healthy young adults were scanned in a 1.5 T MRI scanner while they engaged in the Concurrent Spatial Discrimination Learning Task, a virtual navigation task in which either a spatial or response strategy can be used. In addition to increased BOLD activity in the hippocampus, spatial strategy users showed increased BOLD activity and grey matter density in the ventral area of the medial prefrontal cortex, especially in the orbitofrontal cortex. On the other hand, response strategy users exhibited increased BOLD activity and grey matter density in the dorsal area of the medial prefrontal cortex. Given the prefrontal cortex's role in reward-guided decision-making, we discuss the possibility that the ventromedial prefrontal cortex, including the orbitofrontal cortex, supports spatial learning by encoding stimulus-reward associations, while the dorsomedial prefrontal cortex supports response learning by encoding action-reward associations.

  2. Inmunorreactividad de neuronas gabaergicas y glutamatergicas en la corteza y el cerebelo de ratones infectados con rabia

    OpenAIRE

    Rengifo Castillo, Aura Caterine

    2012-01-01

    La rabia es una enfermedad viral que produce cambios en la función neuronal. Estos cambios, entre otros, inducen alteraciones en el metabolismo de los neurotransmisores. Los signos clínicos de la rabia indican que se podría afectar el sistema GABA-glutamato y, por lo tanto, el balance entre la inhibición y excitación neuronal. El objetivo de este trabajo consistió en evaluar la inmunorreactividad de neuronas GABAérgicas y glutamatérgicas en la corteza y el cerebelo de ratones infectados co...

  3. Efecto dun estímulo potenciador na actividade neuronal da corteza motora, putamen e amígdala

    OpenAIRE

    Montes Lourido, María del Pilar

    2016-01-01

    RESUMO: O presente traballo de investigación propón describir as características da actividade neuronal da corteza premotora, o putamen e a amígdala durante a realización dunha tarefa visuomotora que require dun movemento para recibir unha recompensa. O obxectivo deste traballo é estudar a influenza da presentación de estimulación visual, xunto coa presencia ou ausencia dun estímulo potenciador, na actividade neuronal das citadas áreas. Para realizar este estudo rexistrouse a actividade unita...

  4. Distraction decreases prefrontal oxygenation: A NIRS study.

    Science.gov (United States)

    Ozawa, Sachiyo; Hiraki, Kazuo

    2017-04-01

    When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks.

  5. Prefrontal D1 dopamine signaling is required for temporal control.

    Science.gov (United States)

    Narayanan, Nandakumar S; Land, Benjamin B; Solder, John E; Deisseroth, Karl; DiLeone, Ralph J

    2012-12-11

    Temporal control, or how organisms guide movements in time to achieve behavioral goals, depends on dopamine signaling. The medial prefrontal cortex controls many goal-directed behaviors and receives dopaminergic input primarily from the midbrain ventral tegmental area. However, this system has never been linked with temporal control. Here, we test the hypothesis that dopaminergic projections from the ventral tegmental area to the prefrontal cortex influence temporal control. Rodents were trained to perform a fixed-interval timing task with an interval of 20 s. We report several results: first, that decreasing dopaminergic neurotransmission using virally mediated RNA interference of tyrosine hydroxylase impaired temporal control, and second that pharmacological disruption of prefrontal D1 dopamine receptors, but not D2 dopamine receptors, impaired temporal control. We then used optogenetics to specifically and selectively manipulate prefrontal neurons expressing D1 dopamine receptors during fixed-interval timing performance. Selective inhibition of D1-expressing prefrontal neurons impaired fixed-interval timing, whereas stimulation made animals more efficient during task performance. These data provide evidence that ventral tegmental dopaminergic projections to the prefrontal cortex influence temporal control via D1 receptors. The results identify a critical circuit for temporal control of behavior that could serve as a target for the treatment of dopaminergic diseases.

  6. Advances in understanding ventromedial prefrontal function: the accountant joins the executive.

    Science.gov (United States)

    Fellows, Lesley K

    2007-03-27

    Studies of the brain basis of decision-making and economic behavior are providing a new perspective on the organization and functions of human prefrontal cortex. This line of inquiry has focused particularly on the ventral and medial portions of prefrontal cortex, arguably the most enigmatic regions of the "enigmatic frontal lobes." This review highlights recent advances in the cognitive neuroscience of decision making and neuroeconomics and discusses how these findings can inform clinical thinking about frontal lobe dysfunction.

  7. prefrontal como mecanismo putativo del cambio en psicoterapia

    Directory of Open Access Journals (Sweden)

    Jaime Silva C.

    2005-01-01

    Full Text Available La corteza prefrontal (CPF es definida como la región cerebral cortical que se conecta recíprocamente con el núcleo dorsolateral del tálamo. La visión tradicional en las ciencias del comportamiento atribuye a la CPF un papel en la organización temporal de la conducta. Adicionalmente, estudios convergentes en el campo de la neurociencia afectiva han revelado el papel fundamental que juega la CPF en la determinación del estilo afectivo y en especial de la regulación emocional. El estilo afectivo involucra las diferencias individuales en diferentes parámetros de la reactividad afectiva y el estado de ánimo disposicional (por ejemplo, amplitud de la respuesta emocional, tiempo de recuperación, etc.. Dado que prácticamente todas las alteraciones psicopatológicas incluyen un trastorno en alguno de esos parámetros, proponemos que la modulación de la actividad de la CPF es una variable fundamental del cambio en psicoterapia. Presentamos nuestro modelo putativo, el cual se fundamenta en el control cognitivo en cascada de la CPF. Específicamente, proponemos que la regulación emocional ocurre asociada a la activación de la CPF lateral en un sentido rostralcaudal, donde zonas rostrales involucran formas complejas de control afectivo.

  8. Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control.

    Science.gov (United States)

    Rodrigo, Achala H; Di Domenico, Stefano I; Graves, Bryanna; Lam, Jaeger; Ayaz, Hasan; Bagby, R Michael; Ruocco, Anthony C

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control.

  9. Arthroscopic partial medial meniscectomy

    Directory of Open Access Journals (Sweden)

    Dašić Žarko

    2011-01-01

    Full Text Available Background/Aim. Meniscal injuries are common in professional or recreational sports as well as in daily activities. If meniscal lesions lead to physical impairment they usually require surgical treatment. Arthroscopic treatment of meniscal injuries is one of the most often performed orthopedic operative procedures. Methods. The study analyzed the results of arthroscopic partial medial meniscectomy in 213 patients in a 24-month period, from 2006, to 2008. Results. In our series of arthroscopically treated medial meniscus tears we noted 78 (36.62% vertical complete bucket handle lesions, 19 (8.92% vertical incomplete lesions, 18 (8.45% longitudinal tears, 35 (16.43% oblique tears, 18 (8.45% complex degenerative lesions, 17 (7.98% radial lesions and 28 (13.14% horisontal lesions. Mean preoperative International Knee Documentation Committee (IKDC score was 49.81%, 1 month after the arthroscopic partial medial meniscectomy the mean IKDC score was 84.08%, and 6 months after mean IKDC score was 90.36%. Six months after the procedure 197 (92.49% of patients had good or excellent subjective postoperative clinical outcomes, while 14 (6.57% patients subjectively did not notice a significant improvement after the intervention, and 2 (0.93% patients had no subjective improvement after the partial medial meniscectomy at all. Conclusion. Arthroscopic partial medial meniscetomy is minimally invasive diagnostic and therapeutic procedure and in well selected cases is a method of choice for treatment of medial meniscus injuries when repair techniques are not a viable option. It has small rate of complications, low morbidity and fast rehabilitation.

  10. Organization of prefrontal network activity by respiration-related oscillations

    Science.gov (United States)

    Biskamp, Jonatan; Bartos, Marlene; Sauer, Jonas-Frederic

    2017-01-01

    The medial prefrontal cortex (mPFC) integrates information from cortical and sub-cortical areas and contributes to the planning and initiation of behaviour. A potential mechanism for signal integration in the mPFC lies in the synchronization of neuronal discharges by theta (6–12 Hz) activity patterns. Here we show, using in vivo local field potential (LFP) and single-unit recordings from awake mice, that prominent oscillations in the sub-theta frequency band (1–5 Hz) emerge during awake immobility in the mPFC. These oscillation patterns are distinct from but phase-locked to hippocampal theta activity and occur synchronized with nasal respiration (hence termed prefrontal respiration rhythm [PRR]). PRR activity modulates the amplitude of prefrontal gamma rhythms with greater efficacy than theta oscillations. Furthermore, single-unit discharges of putative pyramidal cells and GABAergic interneurons are entrained by prefrontal PRR and nasal respiration. Our data thus suggest that PRR activity contributes to information processing in the prefrontal neuronal network. PMID:28349959

  11. Reversible antisocial behavior in ventromedial prefrontal lobe epilepsy.

    Science.gov (United States)

    Trebuchon, Agnès; Bartolomei, Fabrice; McGonigal, Aileen; Laguitton, Virginie; Chauvel, Patrick

    2013-11-01

    Frontal lobe dysfunction is known to be associated with impairment in social behavior. We investigated the link between severe pharmacoresistant frontal lobe epilepsy and antisocial trait. We studied four patients with pharmacoresistant epilepsy involving the prefrontal cortex, presenting abnormal interictal social behavior. Noninvasive investigations (video-EEG, PET, MRI) and intracerebral recording (stereoelectroencephalography (SEEG)) were performed as part of a presurgical assessment. Comprehensive psychiatric and cognitive evaluation was performed pre- and postoperatively for frontal lobe epilepsy, with at least 7years of follow-up. All patients shared a characteristic epilepsy pattern: (1) chronic severe prefrontal epilepsy with daily seizures and (2) an epileptogenic zone as defined by intracerebral recording involving the anterior cingulate cortex, ventromedial PFC, and the posterior part of the orbitofrontal cortex, with early propagation to contralateral prefrontal and ipsilateral medial temporal structures. All patients fulfilled the diagnostic criteria (DSM-IV) of antisocial personality disorder, which proved to be reversible following seizure control. Pharmacoresistant epilepsy involving a prefrontal network is associated with antisocial personality. We hypothesize that the occurrence of frequent seizures in this region over a prolonged period produces functional damage leading to impaired prefrontal control of social behavior. This functional damage is reversible since successful epilepsy surgery markedly improved antisocial behavior in these patients. The results are in line with previous reports of impairment of social and moral behavior following ventromedial frontal lobe injury.

  12. [The role of the prefrontal cortex in the sensory problems of children with autism spectrum disorder and its involvement in social aspects].

    Science.gov (United States)

    Martínez-Sanchis, Sonia

    2015-02-25

    Introduccion. En las personas con trastornos del espectro autista (TEA), las percepciones sensoriales aberrantes podrian ser tan caracteristicas y disruptivas como la presencia de anomalias en la comunicacion e interaccion social, asi como de intereses restringidos y repetitivos. La mayoria presenta trastornos de la modulacion sensorial (hiper o hiporresponsividad) en varios canales sensoriales. Ademas, muestra un deficit en la integracion de la informacion procedente de varios sistemas sensoriales (por ejemplo, auditivo y visual). Todo ello agravaria los sintomas nucleares relacionados con la comunicacion y aumentaria la aparicion de problemas conductuales. Objetivo. Revisar la evidencia experimental que aborda el papel de la corteza prefrontal en las experiencias sensoriales inusuales en los TEA y su implicacion en los aspectos sociales. Hay evidencia de hipoactivacion y disfuncion en redes neurales, que incluyen la corteza prefrontal y participan en la cognicion social, como la red por defecto y el sistema de neuronas espejo en niños con TEA. Conclusiones. Los problemas sensoriomotores a edad temprana suponen una disrupcion de la organizacion y regulacion no solo de la percepcion y la accion, sino tambien del lenguaje, el pensamiento, la emocion e incluso la memoria.

  13. ESTUDIO DE LA ACTIVIDAD ENZIMÁTICA DE POLIGALACTURONASA EN LA CORTEZA DE PITAYA AMARILLA (Acanthocereus pitajaya

    Directory of Open Access Journals (Sweden)

    JOHANNA PAOLA RODRÍGUEZ CASTRO

    2006-01-01

    Full Text Available Se determinó la actividad poligalacturonasa en corteza de pitaya amarilla (Acanthocereus pitajaya. El buffer fosfato de sodio 20 mM pH 7,0 con NaCl 0,5 M se constituyó en el sistema más efectivo para la extracción. Se obtuvieron valores óptimos de actividad a pH 5,0 en buffer citratos, a una temperatura de 40 °C. Los valores de KM y VMÁX hallados para esta enzima fueron 2,9 mg ácido poligalacturónico/ml y 0,076 nmol de azúcares reductores/s, respectivamente. Los resultados muestran que la poligalacturonasa está vinculada con el ablandamiento de este fruto.

  14. Arquitectura foliar y anatomía de la corteza y la madera de Quercus sartorii y Q. xalapensis (Fagaceae)

    OpenAIRE

    Dorismilda Martínez Cabrera; Teresa Terrazas; Fernando Zavala Chávez

    2003-01-01

    En este trabajo se describe y compara la arquitectura foliar y la anatomía de la corteza y la madera de Quercus sartorii y Q. xalapensis, especies morfológicamente similares, en la búsqueda de caracteres que contribuyan a su delimitación. Los resultados mostraron que los caracteres del patrón de venación: número y forma de aréolas, ramificación de las vénulas y recorrido de la vena secundaria dentro del diente son caracteres que permiten distinguir a las especies, no así el tamaño de la hoja ...

  15. Estudio de la actividad enzimática poligaracturinasa en la corteza de pitaya amarilla (acanthocereus pitajaya)

    OpenAIRE

    Rodríguez Castro, Johanna Paola; Narváez Cuenca, Carlos Eduardo; Restrepo Sánchez, Luz Patricia

    2011-01-01

    Se determinó la actividad poligalacturonasa en corteza de pitaya amarilla (Acanthocereus pitajaya). El buffer fosfato de sodio 20 mM pH 7,0 con NaCl 0,5 M se constituyó en el sistema más efectivo para la extracción. Se obtuvieron valores óptimos de actividad a pH 5,0 en buffer citratos, a una temperatura de 40 °C. Los valores de KM y VMÁX hallados para esta enzima fueron 2,9 mg ácido poligalacturónico/ml y 0,076 nmol de azúcares reductores/s, respectivamente. Los resultados muestran que la po...

  16. Comparación del contenido de compuestos fenólicos en la corteza de ocho especies de pino

    OpenAIRE

    2003-01-01

    Se evaluó el contenido de taninos condensados y fenoles totales, expresados como ácido tánico, en extractos etanólicos y acuosos de las cortezas de ocho especies de pino abundantes en el estado de Durango. Los extractos etanólicos se obtuvieron por maceración durante 48 h con etanol acuoso al 50 % y los acuosos con agua, a ebullición y reflujo. La evaluación de taninos condensados se realizó mediante el número de Stiasny y los fenoles totales se evaluaron por el método de Folín-Ciocalteu util...

  17. Prefrontal Cortex Lesions and Sex Differences in Fear Extinction and Perseveration

    Science.gov (United States)

    Baran, Sarah E.; Armstrong, Charles E.; Niren, Danielle C.; Conrad, Cheryl D.

    2010-01-01

    Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h…

  18. Coherent theta oscillations and reorganization of spike timing in the hippocampal-prefrontal network upon learning

    NARCIS (Netherlands)

    Benchenane, K.; Peyrache, A.; Khamassi, M.; Tierney, P.L.; Gioanni, Y.; Battaglia, F.P.; Wiener, S.I.

    2010-01-01

    To study the interplay between hippocampus and medial prefrontal cortex (Pfc) and its importance for learning and memory consolidation, we measured the coherence in theta oscillations between these two structures in rats learning new rules on a Y maze. Coherence peaked at the choice point, most stro

  19. Prefrontal Cortex and Neostriatum Self-Stimulation In the Rat : Differential Effects Produced by Apomorphine

    NARCIS (Netherlands)

    Mora, F.; Phillips, A.G.; Koolhaas, J.M.; Rolls, E.T.

    1976-01-01

    In a dose-response experiment, the effects of intraperitoneal injections of the dopamine receptor agonist, apomorphine (0.075, 0.15, 0.3, 0.6 and 1.2 mg/kg) were studied on self-stimulation elicited from electrodes implanted in the medial and sulcal prefrontal cortex and caudate-putamen in the rat.

  20. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings......The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control...

  1. Neuropsychology of prefrontal cortex

    OpenAIRE

    2008-01-01

    The history of clinical frontal lobe study is long and rich which provides valuable insights into neuropsychologic determinants of functions of prefrontal cortex (PFC). PFC is often classified as multimodal association cortex as extremely processed information from various sensory modalities is integrated here in a precise fashion to form the physiologic constructs of memory, perception, and diverse cognitive processes. Human neuropsychologic studies also support the notion of different funct...

  2. Electrophysiological mapping of novel prefrontal - cerebellar pathways

    Directory of Open Access Journals (Sweden)

    Thomas C Watson

    2009-08-01

    Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

  3. Multiple effects of prefrontal lesions on task-switching

    Directory of Open Access Journals (Sweden)

    Tim Shallice

    2008-03-01

    Full Text Available This study examined the performance of 41 patients with focal prefrontal cortical lesions and 38 healthy controls on a task-switching procedure. Three different conditions were evaluated: single tasks without switches and two switching tasks with the currently relevant task signalled either 1500 ms (Long Cue or 200 ms (Short Cue before the stimulus. Patients with Superior Medial lesions showed both a general slowing of reaction time (RT and a signifi cantly increased switch cost as measured by RT. No other prefrontal group showed this increased reaction time switch cost. Increased error rates in the switching conditions, on the other hand, were observed in patients with Inferior Medial lesions and, to a lesser extent, ones with Superior Medial lesions. Patients with left dorsolateral lesions (9/46v showed slower learning of the task as indicated by a high error rate early on. Several different processes are involved in task-switching and these are selectively disrupted by lesions to specifi c areas of the frontal lobes.

  4. Prefrontal-hippocampal pathways underlying inhibitory control over memory.

    Science.gov (United States)

    Anderson, Michael C; Bunce, Jamie G; Barbas, Helen

    2016-10-01

    A key function of the prefrontal cortex is to support inhibitory control over behavior. It is widely believed that this function extends to stopping cognitive processes as well. Consistent with this, mounting evidence establishes the role of the right lateral prefrontal cortex in a clear case of cognitive control: retrieval suppression. Retrieval suppression refers to the ability to intentionally stop the retrieval process that arises when a reminder to a memory appears. Functional imaging data indicate that retrieval suppression involves top-down modulation of hippocampal activity by the dorsolateral prefrontal cortex, but the anatomical pathways supporting this inhibitory modulation remain unclear. Here we bridge this gap by integrating key findings about retrieval suppression observed through functional imaging with a detailed consideration of relevant anatomical pathways observed in non-human primates. Focusing selectively on the potential role of the anterior cingulate cortex, we develop two hypotheses about the pathways mediating interactions between lateral prefrontal cortex and the medial temporal lobes during suppression, and their cellular targets: the entorhinal gating hypothesis, and thalamo-hippocampal modulation via the nucleus reuniens. We hypothesize that whereas entorhinal gating is well situated to stop retrieval proactively, thalamo-hippocampal modulation may interrupt an ongoing act of retrieval reactively. Isolating the pathways that underlie retrieval suppression holds the potential to advance our understanding of a range of psychiatric disorders characterized by persistent intrusive thoughts. More broadly, an anatomical account of retrieval suppression would provide a key model system for understanding inhibitory control over cognition.

  5. Medial canthus retiform hemangioendothelioma

    Directory of Open Access Journals (Sweden)

    Yasser H Al-Faky

    2014-01-01

    Full Text Available Retiform hemangioendothelioma (RH is a distinct entity in the spectrum of vascular tumors with a high local recurrence rate. It is considered a low-grade, well-differentiated cutaneous angiosarcoma with low metastatic potential. We report here for the first time a case of medial canthus recurrent RH. It may be helpful in our practice to include RH as a differential diagnosis of eyelid lesions. It is noteworthy that the progressive course and recurrence tendency of RH might be misdiagnosed as angiosarcoma or basal cell carcinoma (BCC, if not expected and carefully evaluated by the pathologist.

  6. Contribución al estudio experimental del cancer III. Alteraciones de la corteza suprarrenal en la Carcinogenesis Química.

    Directory of Open Access Journals (Sweden)

    Oscar Miro-Quesada C

    1948-12-01

    Full Text Available 1.- Se hace un estudio crítico histo-químico funcional de la corteza suprarrenal en ratones homozigotes C3H (Strong sometidos a la cancerización química con 20-Metilcolantreno. 2.- Se describe un nuevo tipo de reacción funcional de dicha glándula bajo las condiciones experimentales empleadas, sugiriéndose la denominación de "atrofia-hiperactiva", en contraste con las alteraciones histo-químico funcionales de la corteza suprarrenal descritas por varios autores en animales portadores de injertos neoplásicos, las que corresponden al tipo de reacción funcional de la glándula caracterizado por "hipertrofia-hiperactiva". 3.- Los resultados obtenidos sugieren la intervención del sistema endocrino, via la corteza suprarrenal, durante el proceso de carcinogenesis química en el ratón homozigote de raza C3H (Strong.

  7. Precuneus-prefrontal activity during awareness of visual verbal stimuli

    DEFF Research Database (Denmark)

    Kjaer, T W; Nowak, M; Kjær, Klaus Wilbrandt

    2001-01-01

    Awareness is a personal experience, which is only accessible to the rest of world through interpretation. We set out to identify a neural correlate of visual awareness, using brief subliminal and supraliminal verbal stimuli while measuring cerebral blood flow distribution with H(2)(15)O PET....... Awareness of visual verbal stimuli differentially activated medial parietal association cortex (precuneus), which is a polymodal sensory cortex, and dorsolateral prefrontal cortex, which is thought to be primarily executive. Our results suggest participation of these higher order perceptual and executive...... cortical structures in visual verbal awareness....

  8. The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

    Science.gov (United States)

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

    2014-07-01

    The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  10. Infralimbic Prefrontal Cortex Interacts with Nucleus Accumbens Shell to Unmask Expression of Outcome-Selective Pavlovianto- Instrumental Transfer

    Science.gov (United States)

    Keistler, Colby; Barker, Jacqueline M.; Taylor, Jane R.

    2015-01-01

    Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context…

  11. Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia.

    Science.gov (United States)

    Chen, Yi-Wen; Wable, Gauri Satish; Chowdhury, Tara Gunkali; Aoki, Chiye

    2016-06-01

    Many, but not all, adolescent female mice that are exposed to a running wheel while food restricted (FR) become excessive wheel runners, choosing to run even during the hours of food availability, to the point of death. This phenomenon is called activity-based anorexia (ABA). We used electron microscopic immunocytochemistry to ask whether individual differences in ABA resilience may correlate with the lengths of axo-somatic contacts made by GABAergic axon terminals onto layer 5 pyramidal neurons (L5P) in the prefrontal cortex. Contact lengths were, on average, 40% greater for the ABA-induced mice, relative to controls. Correspondingly, the proportion of L5P perikaryal plasma membrane contacted by GABAergic terminals was 45% greater for the ABA mice. Contact lengths in the anterior cingulate cortex correlated negatively and strongly with the overall wheel activity after FR (R = -0.87, P < 0.01), whereas those in the prelimbic cortex correlated negatively with wheel running specifically during the hours of food availability of the FR days (R = -0.84, P < 0.05). These negative correlations support the idea that increases in the glutamic acid decarboxylase (GAD) terminal contact lengths onto L5P contribute toward ABA resilience through suppression of wheel running, a behavior that is intrinsically rewarding and helpful for foraging but maladaptive within a cage.

  12. Relationship between gyrification and functional connectivity of the prefrontal cortex in subjects at high genetic risk of schizophrenia.

    Science.gov (United States)

    Dauvermann, Maria R; Mukherjee, Prerona; Moorhead, William T; Stanfield, Andrew C; Fusar-Poli, Paolo; Lawrie, Stephen M; Whalley, Heather C

    2012-01-01

    Measures of cortical folding ('gyrification') and connectivity are both reported to be disrupted in schizophrenia. There are also reports that increases in prefrontal gyrification may be predictive of subsequent illness in individuals at familial risk of the disorder. Such measures therefore have important potential clinical relevance. The nature of the relationship between cortical morphology and underlying connectivity is however unclear. In the current study we sought to explore the relationship between measures of gyrification and functional connectivity in a cohort of individuals at high genetic risk for the disorder. The theoretical background is based on the hypothesis that increased gyrification index (GI) in the prefrontal cortex may reflect increased short range regional connectivity. The cohort comprised 68 young unaffected relatives of schizophrenia patients and 21 healthy controls. Cortical folding was assessed using an automated Gyrification Index method (A-GI). Participants performed the Hayling sentence completion paradigm in the scanner and measures of functional connectivity were assessed using a correlation based approach. In the high risk subjects significant positive associations were found between prefrontal GI and prefrontal lateral-medial connectivity, while a negative correlation was found between prefrontal GI and prefrontal-thalamic connectivity. These associations indicate that measures describing morphological features of the brain surface relate to measures of underlying functional connectivity in the high risk subjects. Correlations in high risk people were more pronounced than in control subjects. We suggest our previous finding of increased prefrontal gyrification may therefore relate to increased local short range prefrontal connectivity and reduced long range connectivity.

  13. Mindful attention to breath regulates emotions via increased amygdala-prefrontal cortex connectivity.

    Science.gov (United States)

    Doll, Anselm; Hölzel, Britta K; Mulej Bratec, Satja; Boucard, Christine C; Xie, Xiyao; Wohlschläger, Afra M; Sorg, Christian

    2016-07-01

    Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala-prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala-dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice.

  14. Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency.

    Science.gov (United States)

    Labouesse, M A; Lassalle, O; Richetto, J; Iafrati, J; Weber-Stadlbauer, U; Notter, T; Gschwind, T; Pujadas, L; Soriano, E; Reichelt, A C; Labouesse, C; Langhans, W; Chavis, P; Meyer, U

    2016-11-15

    Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN(+) cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.193.

  15. Prelimbic prefrontal cortex mediates respiratory responses to mild and potent prolonged, but not brief, stressors.

    Science.gov (United States)

    Bondarenko, E; Hodgson, D M; Nalivaiko, E

    2014-12-01

    The prefrontal cortex is one of the key areas of the central mechanism of cardiovascular and respiratory control. Disinhibition of the prelimbic medial prefrontal cortex elicits tachypnoeic responses in anesthetized rats (Hassan et al., J. Physiol. 591: 6069-6088, 2013). The current study examines the effects of inhibition of the prelimbic prefrontal cortex during presentation of stressors of various lengths and intensities in conscious unrestrained rats. 8 Wistar rats were implanted with bilateral guide cannulas targeting the prelimbic prefrontal cortex and received microinjections of either saline of GABAA agonist muscimol prior to recording sessions. Inhibition of the prelimbic prefrontal cortex significantly attenuated respiratory responses to a novel environment stress, 30s light stimulus and restraint stress. It did not affect respiratory responses to 500 ms acoustic stimuli of varying intensities (40-90 dB). We conclude that the prelimbic prefrontal cortex contributes to generation of tachypnoeic responses to prolonged stressors, but does not contribute to respiratory arousal in response to brief stressors.

  16. Uso de la corteza del coróngoro Ziziphus amole (Sessé & Moc.) M.C. Johnst. en la medicina tradicional xochipalense

    OpenAIRE

    Pilar América Romero-Castillo; Armando Gómez-Campos; Ma. Cristina Pérez Amador-Barrón; Verónica Muñoz-Ocotero; Alberto Reyes-Dorantes

    2011-01-01

    El objetivo del presente trabajo es valorar el conocimiento y uso medicinal del coróngoro Ziziphus amole (Sessé Moc.) M.C. Johnst. reportado por los habitantes de Xochipala, Guerrero mediante un cuestionario y analizando sus respuestas a través de un análisis estadístico. Se recolectaron frutos, hojas, tallos y corteza, se elaboraron ejemplares botánicos para su confirmación taxonómica. Se realizó un muestreo aleatorio estratificado y se aplicó un cuestionario con preguntas generales a 107 ...

  17. Organización de las interneuronas positivas para parvoalbúmina de la corteza frontopolar en el ser humano: implicaciones para el procesamiento cognitivo y emocional

    Directory of Open Access Journals (Sweden)

    Hernán J. Pimienta J.

    2005-03-01

    Full Text Available La Región frontopolar de la corteza cerebral humana se vincula con el procesamiento explícito y la valoración de los estados mentales internos y externos, la recuperación de la información episódica, la memoria prospectiva y la disociación y reasignación de la atención.  Los mecanismos inhibitorios de las interneuronas que expresan Parvoalbúmina son fundamentales para las anteriores funciones.

  18. Phylogeography, genomics and biosemiotics of bark beetles (Coleoptera: scolytinae) = Filogeografía, genómica y biosemiótica de escarabajos de corteza (Coleoptera: scolytinae)

    OpenAIRE

    Sánchez García, Francisco Javier

    2016-01-01

    Los escarabajos de corteza son insectos unidos a las plantas leñosas. Estos escarabajos están encuadrados dentro de los curculiónidos en la subfamilia Scolytinae. Esta subfamilia está compuesta solamente por insectos fitófagos. Su ciclo vita es crítico en los ciclos de materia y energia de los bosques templados. Además estos insectos pueden afectar a los intereses ecómicos en las zonas donde se producen fenómenos de plaga, las cuales pueden acabar afectando a miles de kilómetros cuadrados de ...

  19. Extracellular matrix plasticity and GABAergic inhibition of prefrontal cortex pyramidal cells facilitates relapse to heroin seeking

    OpenAIRE

    2010-01-01

    Abstract Successful treatment of drug addiction is hampered by high relapse rates during periods of abstinence. Neuroadaptation in the medial prefrontal cortex (mPFC) is thought to play a crucial role in vulnerability to relapse to drug seeking, but the molecular and cellular mechanisms remain largely unknown. To identify protein changes that contribute to relapse susceptibility, we investigated synaptic membrane fractions from the mPFC of rats that underwent 21 days of forced abst...

  20. Dopamine in the medial amygdala network mediates human bonding

    Science.gov (United States)

    Touroutoglou, Alexandra; Rudy, Tali; Salcedo, Stephanie; Feldman, Ruth; Hooker, Jacob M.; Dickerson, Bradford C.; Catana, Ciprian; Barrett, Lisa Feldman

    2017-01-01

    Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers’ dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the “medial amygdala network”) that supports social functioning. We also measured the mothers’ behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother’s infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted. PMID:28193868

  1. Aging affects medial but not anterior frontal learning-related theta oscillations.

    Science.gov (United States)

    van de Vijver, Irene; Cohen, Michael X; Ridderinkhof, K Richard

    2014-03-01

    Aging induces a decline in the ties that bind anatomical networks centered on the prefrontal cortex, which are critical for reinforcement learning and decision making. At the neurophysiological level, the prefrontal cortex may engage electrophysiological oscillatory synchronization to coordinate other brain systems during learning. We recorded scalp EEG from 21 older (mean age 69 years) and 20 young (mean age 22 years) healthy human adults while they learned stimulus-response mappings by trial-and-error using feedback. In young adults, theta-band (4-8 Hz) oscillatory power over medial frontal and anterior frontal cortex predicted learning after errors. Older adults demonstrated a decrease in the theta-band learning-predictive signals over medial frontal but not anterior frontal cortex. This age-related decrease in task-relevant medial frontal theta power may be related to the more general decrease in medial frontal theta power that we observed during rest. These results demonstrate a shift in cortical networks that support reinforcement learning in older adults, and shed new light on the changes in neurophysiological (oscillatory) mechanisms with neurocognitive aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. CONTENIDO DE TANINOS EN LA CORTEZA DE DOS ESPECIES DE PARÁCATA (Erythroxylon compactum Rose y Senna skinneri Benth. Irwin & Barneby

    Directory of Open Access Journals (Sweden)

    Serafín Colín-Urieta

    2013-01-01

    Full Text Available Se obtuvieron taninos de la corteza de Parácata (Erythroxylon compactum Rose y Senna skinneri Benth. Irwin & Barneby mediante extracción acuosa aplicando un diseño experimental 2k, con k = 4 y n = 2. Los factores y niveles fueron: Factor A = tamaño de partícula (0.417, 6.68 mm, Factor B = tiempo de extracción (120, 180 min, Factor C = temperatura de extracción (80, 87 °C, Factor D = relación sólido-líquido (1:15, 1:12. Se evaluó la calidad curtiente de los taninos. Se curtió una piel de venado con taninos de S. skinneri y se determinó la resistencia al desagarre y la resistencia a la tensión. Los resultados de las propiedades físico-mecánicas de la piel curtida fueron superiores a los valores mínimos recomendados por las normas mexicanas. Con base en lo anterior, se estima que la corteza de S. skinneri pudiera ser susceptible de aprovechamiento para la extracción de taninos y así usarlos en el curtido de pieles.

  3. Consenso SECOT artrosis femorotibial medial.

    OpenAIRE

    A. Moreno; Silvestre Muñoz, Antonio; Carpintero, P.

    2013-01-01

    Se presenta un consenso elaborado por SECOT sobre la actuación en la artrosis del compartimento medial de la rodilla para establecer criterios y recomendaciones clínicas orientadas a unificar criterios en su manejo, abordando los factores implicados en la patogenia de la artrosis femorotibial medial de rodilla, la utilidad de las técnicas diagnósticas por la imagen y la utilidad de la artroscopia. También se analizarán los tratamientos conservadores y el tratamiento quirúrgico. Los expertos c...

  4. Injerto libre braquial medial Free medial arm graft

    Directory of Open Access Journals (Sweden)

    P. Martos Díaz

    2007-12-01

    Full Text Available Introducción. Entre las reconstrucciones de defectos titulares de cabeza y cuello, el injerto libre microvascularizado braquial medial no ha adquirido mucha popularidad debido a las variaciones anatómicas que se reflejan en la vascularización de éste. Nuestro objetivo es realizar una descripción de la anatomía y técnica quirúrgica, así como una revisión de la literatura describiendo las ventajas y desventajas de este tipo de injerto. Material y método. Presentamos el caso de una paciente con carcinoma epidermoide de mucosa yugal izquierda con afectación ganglionar ipsilateral. Se procedió a su resección con márgenes más disección cervical funcional. La reconstrucción del defecto se llevó a cabo mediante un injerto libre microvascularizado braquial medial de brazo izquierdo. Discusión. Pensamos que el injerto libre braquial medial de brazo se trata de una opción más segura a la hora de la reconstrucción de defectos cervicofaciales, aportando una serie de ventajas entre las que destacan: no sacrificio de una arteria terminal, cierre primario de la zona donante, mínimo defecto estético, y poseer una piel fina, elástica y sin vello.Introduction. Free medial microvascularized arm grafts have not become very popular for the reconstruction of head and neck defects due to anatomic variations in their vascularization. Our objective was to describe the anatomy and surgical technique and to review the literature on the advantages and disadvantages of free medial arm grafts. Material and methods. We report the case of a patient with squamous cell carcinoma of the left jugal mucosa with same-side lymph node involvement. The tumor was resected with margins and a functional cervical dissection was performed. The defect was reconstructed using a free medial microvascularized graft from the left arm. Discussion. We believe that free medial arm grafts are a safer option for the reconstruction of cervicofacial defects and that they offer

  5. Respuesta de una subpoblación de interneuronas y del transportador glial de glutamato GLT1 en la corteza contralateral a un foco isquémico

    Directory of Open Access Journals (Sweden)

    Adriana M. Medina

    2008-09-01

    Full Text Available Introducción: La isquemia cerebral es una de las formas de lesión cerebral mas frecuentes en el humano. Usualmente los investigadores cuando estudian su fisiopatología se centran en las áreas directamente comprometidas: región del foco, o en las zonas de penumbra, olvidando otros sectores vecinos o no del foco que están conectados con estos sectores de injuria, los cuales pueden estar implicados en algunos de los síntomas que se observan en los pacientes que sufren procesos isquémicos.Objetivo: Evaluar el comportamiento laminar de una subpoblación de interneuronas y de la población glial de la corteza cerebral contralateral al foco isquémico, a través de los marcadores parvalbúmina (PV, que detecta neuronas gabaérgicas y del transportador glial de glutamato GLT1.Materiales y métodos: Se ocluyó la arteria cerebral media derecha en ratas macho adultas, durante 90 minutos, utilizando una sutura intraluminal. Los animales se sacrificaron a las 24 y 72 horas post isquemia. El análisis se hizo en la corteza contralateral al foco, identificando interneuronas PV positivas y la expresión en astrocitos del transportador GLT1.Resultados: Se encontró disminución significativa de la marcación del transportador de glutamato, GLT1, en las capas III y IV de la corteza contralateral al foco isquémico y un aumento en la expresión de PV en las capas II a V comparado con los animales controles.Conclusiones: Los cambios en la expresión de GLT1 pueden proveer un nuevo estado de regulación de glutamato y un patrón diferente de actividad en áreas remotas a un foco isquémico. El aumento en la expresión de PV puede corresponder a un mecanismo adaptativo asociado al incremento de glutamato, por la disminución del transportador, en las envolturas gliales de las sinapsis. Este estudio representa un ejemplo de plasticidad neuronal y glial en zonas remotas al foco isquémico pero conectadas con el mismo.

  6. Prefrontal-hippocampal interactions in memory and emotion

    Directory of Open Access Journals (Sweden)

    Jingji eJin

    2015-12-01

    Full Text Available The hippocampal formation (HPC and medial prefrontal cortex (mPFC have well-established roles in memory encoding and retrieval. However, the mechanisms underlying interactions between the HPC and mPFC in achieving these functions is not fully understood. Considerable research supports the idea that a direct pathway from the HPC and subiculum to the mPFC is critically involved in cognitive and emotional regulation of mnemonic processes. More recently, evidence has emerged that an indirect pathway from the HPC to the mPFC via midline thalamic nucleus reuniens (RE may plays a role in spatial and emotional memory processing. Here we will consider how bidirectional interactions between the HPC and mPFC are involved in working memory, episodic memory and emotional memory in animals and humans. We will also consider how dysfunctions in bidirectional HPC-mPFC pathways contribute to psychiatric disorders.

  7. Amphetamines modulate prefrontal γ oscillations during attention processing.

    Science.gov (United States)

    Franzen, John D; Wilson, Tony W

    2012-08-22

    Amphetamine-based medications robustly suppress symptoms of attention-deficit/hyperactivity disorder (ADHD), but their exact mechanisms remain poorly understood. Recent hemodynamic imaging studies have suggested that amphetamines may modulate the prefrontal and anterior cingulate brain regions, although few studies have been published and the results have not been entirely consistent. Meanwhile, several electrophysiological studies have shown that abnormal fast oscillations (in the γ range) may be closely linked to inattention and other cardinal symptoms of ADHD. In this study, we utilized magnetoencephalography to examine how amphetamines modulate high-frequency brain activity in adults with ADHD. Participants performed an auditory attention task, which required sustained attention in one block and passive listening in a separate block. Participants completed the task twice in the on-medication and off-medication states. All data were analyzed using beamforming techniques to resolve cortical regions showing event-related synchronizations and desynchronizations. Our primary findings indicated that oral administration of amphetamine decreased γ-band event-related desynchronization activity significantly in the medial prefrontal area and decreased event-related synchronization in bilateral superior parietal areas, left inferior parietal, and the left inferior frontal gyrus. These results suggest that psychostimulants strongly modulate γ activity in frontal and parietal cortical areas, which are known to be central to the brain's core attentional networks.

  8. Reality monitoring impairment in schizophrenia reflects specific prefrontal cortex dysfunction

    Directory of Open Access Journals (Sweden)

    Jane R. Garrison

    2017-01-01

    Full Text Available Reality monitoring impairment is often reported in schizophrenia but the neural basis of this deficit is poorly understood. Difficulties with reality monitoring could be attributable to the same pattern of neural dysfunction as other cognitive deficits that characterize schizophrenia, or might instead represent a separable and dissociable impairment. This question was addressed through direct comparison of behavioral performance and neural activity associated with reality monitoring and working memory in patients with schizophrenia and matched healthy controls. Participants performed a word-pair reality monitoring task and a Sternberg working memory task while undergoing fMRI scanning. Distinct behavioral deficits were observed in the patients during performance of each task, which were associated with separable task- and region-specific dysfunction in the medial anterior prefrontal cortex for reality monitoring and dorsolateral prefrontal cortex for working memory. The results suggest that reality monitoring impairment is a distinct neurocognitive deficit in schizophrenia. The findings are consistent with the presence of a range of dissociable cognitive deficits in schizophrenia which may be associated with variable functional and structural dysconnectivity in underlying processing networks.

  9. Multiple anatomical systems embedded within the primate medial temporal lobe: implications for hippocampal function.

    Science.gov (United States)

    Aggleton, John P

    2012-08-01

    A review of medial temporal lobe connections reveals three distinct groupings of hippocampal efferents. These efferent systems and their putative memory functions are: (1) The 'extended-hippocampal system' for episodic memory, which involves the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for affective and social learning, which involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and integration, which originates from the length of CA1 and the subiculum, and is characterised by columnar, connections with reciprocal topographies. A fourth system, the 'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval processing, has more widespread prefrontal connections than those of the hippocampus, along with different thalamic inputs. Despite many interactions between these four systems, they may retain different roles in memory which when combined explain the importance of the medial temporal lobe for the formation of declarative memories.

  10. Injerto libre braquial medial Free medial arm graft

    OpenAIRE

    2007-01-01

    Introducción. Entre las reconstrucciones de defectos titulares de cabeza y cuello, el injerto libre microvascularizado braquial medial no ha adquirido mucha popularidad debido a las variaciones anatómicas que se reflejan en la vascularización de éste. Nuestro objetivo es realizar una descripción de la anatomía y técnica quirúrgica, así como una revisión de la literatura describiendo las ventajas y desventajas de este tipo de injerto. Material y método. Presentamos el caso de una paciente con ...

  11. Bilinearity, rules, and prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Peter Dayan

    2007-11-01

    Full Text Available Humans can be instructed verbally to perform computationally complex cognitive tasks; their performance then improves relatively slowly over the course of practice. Many skills underlie these abilities; in this paper, we focus on the particular question of a uniform architecture for the instantiation of habitual performance and the storage, recall, and execution of simple rules. Our account builds on models of gated working memory, and involves a bilinear architecture for representing conditional input-output maps and for matching rules to the state of the input and working memory. We demonstrate the performance of our model on two paradigmatic tasks used to investigate prefrontal and basal ganglia function.

  12. Medial Prefrontal Cortex Activation Facilitates Re-Extinction of Fear in Rats

    Science.gov (United States)

    Chang, Chun-hui; Maren, Stephen

    2011-01-01

    It has been suggested that reduced infralimbic (IL) cortical activity contributes to impairments of fear extinction. We therefore explored whether pharmacological activation of the IL would facilitate extinction under conditions it normally fails (i.e., immediate extinction). Rats received auditory fear conditioning 1 h before extinction training.…

  13. Differential Involvement of the Medial Prefrontal Cortex across Variants of Contextual Fear Conditioning

    Science.gov (United States)

    Heroux, Nicholas A.; Robinson-Drummer, Patrese A.; Sanders, Hollie R.; Rosen, Jeffrey B.; Stanton, Mark E.

    2017-01-01

    The context preexposure facilitation effect (CPFE) is a contextual fear conditioning paradigm in which learning about the context, acquiring the context-shock association, and retrieving/expressing contextual fear are temporally dissociated into three distinct phases. In contrast, learning about the context and the context-shock association…

  14. Striatum-medial prefrontal cortex connectivity predicts developmental changes in reinforcement learning

    NARCIS (Netherlands)

    van den Bos, W.; Cohen, M.X.; Kahnt, T.; Crone, E.A.

    2012-01-01

    During development, children improve in learning from feedback to adapt their behavior. However, it is still unclear which neural mechanisms might underlie these developmental changes. In the current study, we used a reinforcement learning model to investigate neurodevelopmental changes in the repre

  15. The Role of the Medial Prefrontal Cortex in Trace Fear Extinction

    Science.gov (United States)

    Kwapis, Janine L.; Jarome, Timothy J.; Helmstetter, Fred J.

    2015-01-01

    The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that…

  16. The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Medial Prefrontal Cortex in Autism.

    OpenAIRE

    E. Hashemi; Ariza, J.; Rogers, H.; Noctor, SC; Martínez-Cerdeño, V

    2016-01-01

    The cognitive phenotype of autism has been correlated with an altered balance of excitation to inhibition in the cerebral cortex, which could result from a change in the number, function, or morphology of GABA-expressing interneurons. The number of GABAergic interneuron subtypes has not been quantified in the autistic cerebral cortex. We classified interneurons into 3 subpopulations based on expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin. We quantified the nu...

  17. Medial Prefrontal Cortex Activation Facilitates Re-Extinction of Fear in Rats

    Science.gov (United States)

    Chang, Chun-hui; Maren, Stephen

    2011-01-01

    It has been suggested that reduced infralimbic (IL) cortical activity contributes to impairments of fear extinction. We therefore explored whether pharmacological activation of the IL would facilitate extinction under conditions it normally fails (i.e., immediate extinction). Rats received auditory fear conditioning 1 h before extinction training.…

  18. Gap Junctions in the Ventral Hippocampal-Medial Prefrontal Pathway Are Involved in Anxiety Regulation

    Science.gov (United States)

    Schoenfeld, Timothy J.; Kloth, Alexander D.; Hsueh, Brian; Runkle, Matthew B.; Kane, Gary A.; Wang, Samuel S.-H.

    2014-01-01

    Anxiety disorders are highly prevalent but little is known about their underlying mechanisms. Gap junctions exist in brain regions important for anxiety regulation, such as the ventral hippocampus (vHIP) and mPFC, but their functions in these areas have not been investigated. Using pharmacological blockade of neuronal gap junctions combined with electrophysiological recordings, we found that gap junctions play a role in theta rhythm in the vHIP and mPFC of adult mice. Bilateral infusion of neuronal gap junction blockers into the vHIP decreased anxiety-like behavior on the elevated plus maze and open field. Similar anxiolytic effects were observed with unilateral infusion of these drugs into the vHIP combined with contralateral infusion into the mPFC. No change in anxious behavior was observed with gap junction blockade in the unilateral vHIP alone or in the bilateral dorsal HIP. Since physical exercise is known to reduce anxiety, we examined the effects of long-term running on the expression of the neuronal gap junction protein connexin-36 among inhibitory interneurons and found a reduction in the vHIP. Despite this change, we observed no alteration in theta frequency or power in long-term runners. Collectively, these findings suggest that neuronal gap junctions in the vHIP–mPFC pathway are important for theta rhythm and anxiety regulation under sedentary conditions but that additional mechanisms are likely involved in running-induced reduction in anxiety. PMID:25411496

  19. Medial Prefrontal Lesions in Mice Impair Sustained Attention but Spare Maintenance of Information in Working Memory

    Science.gov (United States)

    Kahn, Julia B.; Ward, Ryan D.; Kahn, Lora W.; Rudy, Nicole M.; Kandel, Eric R.; Balsam, Peter D.; Simpson, Eleanor H.

    2012-01-01

    Working memory and attention are complex cognitive functions that are disrupted in several neuropsychiatric disorders. Mouse models of such human diseases are commonly subjected to maze-based tests that can neither distinguish between these cognitive functions nor isolate specific aspects of either function. Here, we have adapted a simple visual…

  20. Inactivation of Medial Prefrontal Cortex or Acute Stress Impairs Odor Span in Rats

    Science.gov (United States)

    Davies, Don A.; Molder, Joel J.; Greba, Quentin; Howland, John G.

    2013-01-01

    The capacity of working memory is limited and is altered in brain disorders including schizophrenia. In rodent working memory tasks, capacity is typically not measured (at least not explicitly). One task that does measure working memory capacity is the odor span task (OST) developed by Dudchenko and colleagues. In separate experiments, the effects…

  1. Dynamic Expression of FKBP5 in the Medial Prefrontal Cortex Regulates Resiliency to Conditioned Fear

    Science.gov (United States)

    Criado-Marrero, Marangelie; Morales Silva, Roberto J.; Velazquez, Bethzaly; Hernández, Anixa; Colon, María; Cruz, Emmanuel; Soler-Cedeño, Omar; Porter, James T.

    2017-01-01

    The factors influencing resiliency to the development of post-traumatic stress disorder (PTSD) remain to be elucidated. Clinical studies associate PTSD with polymorphisms of the FK506 binding protein 5 (FKBP5). However, it is unclear whether changes in FKBP5 expression alone could produce resiliency or susceptibility to PTSD-like symptoms. In this…

  2. Localized Disruption of Narp in Medial Prefrontal Cortex Blocks Reinforcer Devaluation Performance

    Science.gov (United States)

    Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.

    2010-01-01

    Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates [alpha]-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this…

  3. Effective amygdala-prefrontal connectivity predicts individual differences in successful emotion regulation.

    Science.gov (United States)

    Morawetz, Carmen; Bode, Stefan; Baudewig, Juergen; Heekeren, Hauke R

    2016-12-20

    The ability to voluntarily regulate our emotional response to threatening and highly arousing stimuli by using cognitive reappraisal strategies is essential for our mental and physical well-being. This might be achieved by prefrontal brain regions (e.g., inferior frontal gyrus, IFG) down-regulating activity in the amygdala. It is unknown, to which degree effective connectivity within the emotion-regulation network is linked to individual differences in reappraisal skills. Using psychophysiological interaction (PPI) analyses of functional magnetic resonance imaging data, we examined changes in inter-regional connectivity between the amygdala and IFG with other brain regions during reappraisal of emotional responses and used emotion regulation success as an explicit regressor. During down-regulation of emotion, reappraisal success correlated with effective connectivity between IFG with dorsolateral, dorsomedial and ventromedial prefrontal cortex (PFC). During up-regulation of emotion, effective coupling between IFG with anterior cingulate cortex, dorsomedial and ventromedial PFC as well as the amygdala correlated with reappraisal success. Activity in the amygdala covaried with activity in lateral and medial prefrontal regions during the up-regulation of emotion and correlated with reappraisal success. These results suggest that successful reappraisal is linked to changes in effective connectivity between two systems, prefrontal cognitive control regions and regions crucially involved in emotional evaluation.

  4. Back to front: cerebellar connections and interactions with the prefrontal cortex

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    Thomas C Watson

    2014-02-01

    Full Text Available Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN in awake, behaving rats evokes distinct local field potential (LFP responses (onset latency ~13 ms in the prelimbic (PrL subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anaesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5-10 Hz. Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.

  5. Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats.

    Science.gov (United States)

    Sajja, Venkata Siva Sai Sujith; Perrine, Shane A; Ghoddoussi, Farhad; Hall, Christina S; Galloway, Matthew P; VandeVord, Pamela J

    2014-03-01

    Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, pinositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory.

  6. Prefrontal NMDA receptors expressed in excitatory neurons control fear discrimination and fear extinction.

    Science.gov (United States)

    Vieira, Philip A; Corches, Alex; Lovelace, Jonathan W; Westbrook, Kevin B; Mendoza, Michael; Korzus, Edward

    2015-03-01

    N-methyl-D-aspartate receptors (NMDARs) are critically involved in various learning mechanisms including modulation of fear memory, brain development and brain disorders. While NMDARs mediate opposite effects on medial prefrontal cortex (mPFC) interneurons and excitatory neurons, NMDAR antagonists trigger profound cortical activation. The objectives of the present study were to determine the involvement of NMDARs expressed specifically in excitatory neurons in mPFC-dependent adaptive behaviors, specifically fear discrimination and fear extinction. To achieve this, we tested mice with locally deleted Grin1 gene encoding the obligatory NR1 subunit of the NMDAR from prefrontal CamKIIα positive neurons for their ability to distinguish frequency modulated (FM) tones in fear discrimination test. We demonstrated that NMDAR-dependent signaling in the mPFC is critical for effective fear discrimination following initial generalization of conditioned fear. While mice with deficient NMDARs in prefrontal excitatory neurons maintain normal responses to a dangerous fear-conditioned stimulus, they exhibit abnormal generalization decrement. These studies provide evidence that NMDAR-dependent neural signaling in the mPFC is a component of a neural mechanism for disambiguating the meaning of fear signals and supports discriminative fear learning by retaining proper gating information, viz. both dangerous and harmless cues. We also found that selective deletion of NMDARs from excitatory neurons in the mPFC leads to a deficit in fear extinction of auditory conditioned stimuli. These studies suggest that prefrontal NMDARs expressed in excitatory neurons are involved in adaptive behavior.

  7. Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood

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    Huib eMansvelder

    2012-08-01

    Full Text Available The majority of adolescents report to have smoked a cigarette at least once. Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC, is still ongoing. Tobacco smoking during this age may compromise the normal course of prefrontal development and lead to cognitive impairments in later life. In addition, adolescent smokers suffer from attention deficits, which progress with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and underlie the lasting effects on cognitive function. In particular, the expression and function of metabotropic glutamate receptors (mGluRs are changed and this has an impact on short- and long-term plasticity of glutamatergic synapses in the PFC and ultimately on the attention performance. Here, we review and discuss these recent findings.

  8. Brief dopaminergic stimulations produce transient physiological changes in prefrontal pyramidal neurons.

    Science.gov (United States)

    Moore, Anna R; Zhou, Wen-Liang; Potapenko, Evgeniy S; Kim, Eun-Ji; Antic, Srdjan D

    2011-01-25

    In response to food reward and other pertinent events, midbrain dopaminergic neurons fire short bursts of action potentials causing a phasic release of dopamine in the prefrontal cortex (rapid and transient increases in cortical dopamine concentration). Here we apply short (2s) iontophoretic pulses of glutamate, GABA, dopamine and dopaminergic agonists locally, onto layer 5 pyramidal neurons in brain slices of the rat medial prefrontal cortex (PFC). Unlike glutamate and GABA, brief dopaminergic pulses had negligible effects on the resting membrane potential. However, dopamine altered action potential firing in an extremely rapid (iontophoresis current artifact. Our present data imply that one population of PFC pyramidal neurons receiving direct synaptic contacts from midbrain dopaminergic neurons would stall during the 0.5s of the phasic dopamine burst. The spillover dopamine, on the other hand, would act as a positive stimulator of cortical excitability (30% increase) to all D2-receptor carrying pyramidal cells, for the next 40s.

  9. Acute Medial Plantar Fascia Tear.

    Science.gov (United States)

    Pascoe, Stephanie C; Mazzola, Timothy J

    2016-06-01

    A 32-year-old man who participated in competitive soccer came to physical therapy via direct access for a chief complaint of plantar foot pain. The clinical examination findings and mechanism of injury raised a concern for a plantar fascia tear, so the patient was referred to the physician and magnetic resonance imaging was obtained. The magnetic resonance image confirmed a high-grade, partial-thickness, proximal plantar fascia tear with localized edema at the location of the medial band. J Orthop Sports Phys Ther 2016;46(6):495. doi:10.2519/jospt.2016.0409.

  10. Medial orbitofrontal cortex lesion prevents facilitatory effects of d-cycloserine during fear extinction.

    Science.gov (United States)

    Sierra, Rodrigo O; Nítola, Laura P; Duran, Johanna M; Prieto, Daysi R; León, Laura A; Cardenas, Fernando P

    2016-01-01

    Animal models of fear extinction have an important clinical relevance to pharmacological and exposure-based therapies for anxiety disorders. Lesions of prefrontal structures impair fear extinction. On the other hand, d-cycloserine is able to enhance this process. We hypothesize that the integrity of cortical structures involved in inhibitory control of emotional responses is crucial for the facilitatory effects of d-cycloserine. Here, we showed that medial orbitofrontal cortex lesion prevents d-cycloserine enhancement of fear extinction. These preliminary results suggest that effects of pharmacological treatments could be dependent on cortical activity state to promote fear memory reduction.

  11. Mapping Prefrontal Cortex Functions in Human Infancy

    Science.gov (United States)

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  12. Cinética de lixiviación de la corteza de mangle rojo en agua Leaching kinetics of the red mangrove bark in water

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    Yanet Rodríguez Perdomo

    2012-03-01

    Full Text Available Objetivo: determinar la naturaleza del fenómeno que rige la transferencia de masa durante la lixiviación del mangle rojo en agua mediante el estudio de la cinética del proceso. Métodos: se estudió la cinética de lixiviación de la corteza de mangle rojo en agua a escala de laboratorio, en una relación sólido/líquido 1:4 a diferentes temperaturas (25, 45, 70 y 90 °C. Para cada temperatura en particular se determinó la constante cinética a partir de la ecuación fundamental de la lixiviación mediante un modelo ajustado empleando el programa estadístico CurveExpert 1.4 para Windows. Resultados: los valores de la concentración de sólidos solubles totales correspondientes a 25 y 45 °C presentaron un incremento apreciable durante los primeros 20 min, y los correspondientes a 70 y 90 °C lo alcanzaron a los 30 min. El valor de la energía de activación obtenida en el experimento correspondió a 2,884 kJ. Conclusiones: la naturaleza de la lixiviación de la corteza de mangle rojo se produce por vía física.Objective: to determine the type of phenomenon ruling the mass transfer during leaching of red mangrove in water by studying the kinetics of this process. Methods: the kinetics of leaching of red mangrove bark into water at lab was studied in a solid/liquid ratio of 1:4 at different temperatures (25, 45, 70 and 90 ºC. For each temperature, the kinetic constant was estimated from the fundamental leaching equation by a fitted model using the statistical program CurveExpert 1.4 for Windows. Results: the total soluble solid concentration values showed a sizeable increase at 25 and 45 °C in the first 20 minutes and at 70 and 90 °C in 30 minutes. The activation energy in the experiment amounted to 2.884 kJ. Conclusions: the leaching of the red mangrove bark is of physical origin.

  13. Variant position of the medial plantar nerve

    OpenAIRE

    Astik RB; Dave UH; Gajendra KS

    2011-01-01

    Knowledge of variation of position of the medial plantar nerve is important for the forefoot surgeon for plantar reconstruction, local injection therapy and an excision of interdigital neuroma. During routine dissection of 50-year-old female cadaver, we found the medial plantar nerve and vessels variably located between plantar aponeurosis and the muscles of the first layer of the sole of the right foot. Due to this variant position, the medial plantar nerve and vessels lose their protection ...

  14. Snapping Knee Caused by Medial Meniscal Cyst

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    Tsuyoshi Ohishi

    2014-01-01

    Full Text Available Snapping phenomenon around the medial aspect of the knee is rare. We present this case of snapping knee caused by the sartorius muscle over a large medial meniscal cyst in a 66-year-old female. Magnetic resonance images demonstrated a large medial meniscal cyst with a horizontal tear of the medial meniscus. Arthroscopic cyst decompression with limited meniscectomy resulted in the disappearance of snapping, and no recurrence of the cyst was observed during a 2-year follow-up period.

  15. Differences in prefrontal, limbic, and white matter lesion volumes according to cognitive status in elderly patients with first-onset subsyndromal depression.

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    Jun-Young Lee

    Full Text Available The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI and Alzheimer's disease (AD. We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59, MCI (n = 27, and AD (n = 27, adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.

  16. Neurotoxic lesions of the medial mediodorsal nucleus of the thalamus disrupt reinforcer devaluation effects in rhesus monkeys.

    Science.gov (United States)

    Mitchell, Anna S; Browning, Philip G F; Baxter, Mark G

    2007-10-17

    The mediodorsal thalamus is a major input to the prefrontal cortex and is thought to modulate cognitive functions of the prefrontal cortex. Damage to the medial, magnocellular part of the mediodorsal thalamus (MDmc) impairs cognitive functions dependent on prefrontal cortex, including memory. The contribution of MDmc to other aspects of cognition dependent on prefrontal cortex has not been determined. The ability of monkeys to adjust their choice behavior in response to changes in reinforcer value, a capacity impaired by lesions of orbital prefrontal cortex, can be tested in a reinforcer devaluation paradigm. In the present study, rhesus monkeys with bilateral neurotoxic MDmc lesions were tested in the devaluation procedure. Monkeys learned visual discrimination problems in which each rewarded object is reliably paired with one of two different food rewards and then were given choices between pairs of rewarded objects, one associated with each food. Selective satiation of one of the food rewards reduces choices of objects associated with that food in normal monkeys. Monkeys with bilateral neurotoxic lesions of MDmc learned concurrently presented visual discrimination problems as quickly as unoperated control monkeys but showed impaired reinforcer devaluation effects. This finding suggests that the neural circuitry for control of behavioral choice by changes in reinforcer value includes MDmc.

  17. Predicting Treatment Outcomes from Prefrontal Cortex Activation for Self-Harming Patients with Borderline Personality Disorder: A Preliminary Study

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    Anthony Charles Ruocco

    2016-05-01

    Full Text Available Self-harm is a potentially lethal symptom of borderline personality disorder (BPD that often improves with dialectical behavior therapy (DBT. While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, twenty-nine actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex during impulse control prior to beginning DBT and after seven months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex prior to beginning treatment, and they showed the greatest increases in activity within this region after seven months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial prefrontal cortex and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right dorsolateral prefrontal cortex even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the prefrontal cortex underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT.

  18. Polygalacturonase Activity in Yellow Pitaya Peel (Acanthocereus pitajaya Estudio de la actividad enzimática poligaracturinasa en la corteza de pitaya amarilla (Acanthocereus pitajaya

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    Narváez Cuenca Carlos Eduardo

    2006-12-01

    Full Text Available Polygalacturonase activity was determinated in yellow pitaya fruit (Acanthocereus pitajaya. Protein concentrations and activities of the enzyme in the extracts weredetermined. Buffer sodium phosphate 20 mM pH 7,0 with NaCl 0,5 M was the most effective extraction system. The enzyme exhibited optimum activity at pH 5,0 in buffer citrate at 40 °C. The KM of the enzyme was 2.9 mg/mL for polygalacturonic acid and VMÁX of 0.076 nmol of reducing groups/s. Results show that polygalacturonase is related with softening on yellow pitaya fruit.Se determinó la actividad poligalacturonasa en corteza de pitaya amarilla (Acanthocereus pitajaya. El buffer fosfato de sodio 20 mM pH 7,0 con NaCl 0,5 M se constituyó en el sistema más efectivo para la extracción. Se obtuvieron valores óptimos de actividad a pH 5,0 en buffer citratos, a una temperatura de 40 °C. Los valores de KM y VMÁX hallados para esta enzima fueron 2,9 mg ácido poligalacturónico/ml y 0,076 nmol de azúcares reductores/s, respectivamente. Los resultados muestran que la poligalacturonasa está vinculada con el ablandamiento de este fruto.

  19. ESTUDIO DE LA ACTIVIDAD ENZIMÁTICA DE POLIGALACTURONASA EN LA CORTEZA DE PITAYA AMARILLA (Acanthocereus pitajaya Polygalacturonase Activity in Yellow Pitaya Peel (Acanthocereus pitajaya

    Directory of Open Access Journals (Sweden)

    JOHANNA PAOLA RODRÍGUEZ CASTRO

    Full Text Available Se determinó la actividad poligalacturonasa en corteza de pitaya amarilla (Acanthocereus pitajaya. El buffer fosfato de sodio 20 mM pH 7,0 con NaCl 0,5 M se constituyó en el sistema más efectivo para la extracción. Se obtuvieron valores óptimos de actividad a pH 5,0 en buffer citratos, a una temperatura de 40 °C. Los valores de KM y VMÁX hallados para esta enzima fueron 2,9 mg ácido poligalacturónico/ml y 0,076 nmol de azúcares reductores/s, respectivamente. Los resultados muestran que la poligalacturonasa está vinculada con el ablandamiento de este fruto.Polygalacturonase activity was determinated in yellow pitaya fruit (Acanthocereus pitajaya. Protein concentrations and activities of the enzyme in the extracts were determined. Buffer sodium phosphate 20 mM pH 7,0 with NaCl 0,5 M was the most effective extraction system. The enzyme exhibited optimum activity at pH 5,0 in buffer citrate at 40 °C. The KM of the enzyme was 2.9 mg/mL for polygalacturonic acid and VMÁX of 0.076 nmol of reducing groups/s. Results show that polygalacturonase is related with softening on yellow pitaya fruit.

  20. Power spectrum scale invariance identifies prefrontal dysregulation in paranoid schizophrenia.

    Science.gov (United States)

    Radulescu, Anca R; Rubin, Denis; Strey, Helmut H; Mujica-Parodi, Lilianne R

    2012-07-01

    Theory and experimental evidence suggest that complex living systems function close to the boundary of chaos, with erroneous organization to an improper dynamical range (too stiff or chaotic) underlying system-wide dysregulation and disease. We hypothesized that erroneous organization might therefore also characterize paranoid schizophrenia, via optimization abnormalities in the prefrontal-limbic circuit regulating emotion. To test this, we acquired fMRI scans from 35 subjects (N = 9 patients with paranoid schizophrenia and N = 26 healthy controls), while they viewed affect-valent stimuli. To quantify dynamic regulation, we analyzed the power spectrum scale invariance (PSSI) of fMRI time-courses and computed the geometry of time-delay (Poincaré) maps, a measure of variability. Patients and controls showed distinct PSSI in two clusters (k(1) : Z = 4.3215, P = 0.00002 and k(2) : Z = 3.9441, P = 0.00008), localized to the orbitofrontal/medial prefrontal cortex (Brodmann Area 10), represented by β close to white noise in patients (β ≈ 0) and in the pink noise range in controls (β ≈ -1). Interpreting the meaning of PSSI differences, the Poincaré maps indicated less variability in patients than controls (Z = -1.9437, P = 0.05 for k(1) ; Z = -2.5099, P = 0.01 for k(2) ). That the dynamics identified Brodmann Area 10 is consistent with previous schizophrenia research, which implicates this area in deficits of working memory, executive functioning, emotional regulation and underlying biological abnormalities in synaptic (glutamatergic) transmission. Our results additionally cohere with a large body of work finding pink noise to be the normal range of central function at the synaptic, cellular, and small network levels, and suggest that patients show less supple responsivity of this region.

  1. Medial Patella Subluxation: Diagnosis and Treatment

    Science.gov (United States)

    McCarthy, Mark A.; Bollier, Mathew J.

    2015-01-01

    Medial patella subluxation is a disabling condition typically associated with previous patellofemoral instability surgery. Patients often describe achy pain with painful popping episodes. They often report that the patella shifts laterally, which occurs as the medial subluxed patella dramatically shifts into the trochlear groove during early knee flexion. Physical examination is diagnostic with a positive medial subluxation test. Nonoperative treatment, such as focused physical therapy and patellofemoral stabilizing brace, is often unsuccessful. Primary surgical options include lateral retinacular repair/imbrication or lateral reconstruction. Prevention is key to avoid medial patella subluxation. When considering patellofemoral surgery, important factors include appropriate lateral release indications, consideration of lateral retinacular lengthening vs release, correct MPFL graft placement and tension, and avoiding excessive medialization during tubercle transfer. This review article will analyze patient symptoms, diagnostic exam findings and appropriate treatment options, as well as pearls to avoid this painful clinical entity. PMID:26361441

  2. The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial Direct Current Stimulation

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    Lisa Bellaïche

    2013-01-01

    Full Text Available Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN and error positivity (Pe originating from the medial prefrontal cortex (mPFC. Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS. Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits.

  3. Prefrontal cortex glutamate and extraversion.

    Science.gov (United States)

    Grimm, Simone; Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-10-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states.

  4. Variant position of the medial plantar nerve

    Directory of Open Access Journals (Sweden)

    Astik RB

    2011-01-01

    Full Text Available Knowledge of variation of position of the medial plantar nerve is important for the forefoot surgeon for plantar reconstruction, local injection therapy and an excision of interdigital neuroma. During routine dissection of 50-year-old female cadaver, we found the medial plantar nerve and vessels variably located between plantar aponeurosis and the muscles of the first layer of the sole of the right foot. Due to this variant position, the medial plantar nerve and vessels lose their protection from the muscles of the first layer of the sole of the foot and became vulnerable for compression.

  5. Medial talo-calcaneal coalition. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Daly, B.D.; Towers, M.J.; Hamilton, S.

    1988-11-01

    Medial talo-calcaneal coalition is an uncommon developmental anomaly consisting of a bony projection arising from the postero-medial aspect of the sustentaculum tali, which may articulate with another bony projection from the medial aspect of the talus. Fibrous, cartilaginous or bony ankylosis may occur. It usually presents in adolescents, and causes pain following exercise. It may cause a lump, and can predispose to flat foot and early osteoarthrosis. This condition is easily overlooked on routine views of the ankle, and may require oblique views and tomography for its detection and clarification.

  6. Changes in prefrontal-limbic function in major depression after 15 months of long-term psychotherapy.

    Science.gov (United States)

    Buchheim, Anna; Viviani, Roberto; Kessler, Henrik; Kächele, Horst; Cierpka, Manfred; Roth, Gerhard; George, Carol; Kernberg, Otto F; Bruns, Georg; Taubner, Svenja

    2012-01-01

    Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

  7. Changes in prefrontal-limbic function in major depression after 15 months of long-term psychotherapy.

    Directory of Open Access Journals (Sweden)

    Anna Buchheim

    Full Text Available Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV unmedicated outpatients (N = 16 and control participants matched for sex, age, and education (N = 17 before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

  8. Desarrollo de un Adsorbente Basado en Taninos de Corteza de Pinus pinaster Development of an Adsorbent Based on Tannins from Pinus pinaster Bark

    Directory of Open Access Journals (Sweden)

    G. Vázquez

    2005-01-01

    Full Text Available Se han preparado partículas de gel de taninos de corteza de Pinus pinaster empleando un proceso en dos etapas. En la primera etapa (de pre unión cruzada, los taninos reaccionan con formaldehído. En la segunda (de granulación, la disolución taninos-formaldehído parcialmente gelificada se dispersa sobre una mezcla de decalina y un agente tensoactivo no iónico. Se ha analizado la influencia de las condiciones de operación de ambas etapas sobre el rendimiento y características de las partículas obtenidas. Las partículas, ligeramente porosas y prácticamente esféricas, se han empleado para la adsorción de cadmio de disoluciones acuosas. Los espectros de dispersión de rayos X obtenidos tras la adsorción han confirmado la presencia de cadmio sobre la superficie de las partículas y, por tanto, su capacidad para la adsorción de cationes metálicos.Tannin-gel particles, based on tannins extracted from Pinus pinaster bark, have been prepared in a two-stage process. In the first stage (pre-crosslinking, tannins react with formaldehyde. In the second stage (granulation, the partially gelled tannin-formaldehyde solution is dispersed into a mixture of decalin and a non-ionic surfactant. The influence of operation conditions of both stages on the yield and characteristics of the particles has been analysed. The particles, slightly porous and nearly spherical, have been used to adsorb cadmium from aqueous solutions. X-ray energy dispersion spectra obtained after adsorption have confirmed the presence of cadmium on particle surface and, therefore, their capacity for metal cation adsorption.

  9. Interactions of the hippocampal system and the prefrontal cortex in learning language-like rules.

    Science.gov (United States)

    Opitz, Bertram; Friederici, Angela D

    2003-08-01

    One of the most influential views on the hippocampal function suggests that this brain region is critically involved in relational memory processing, that is, binding converging inputs to mediate the representation of relationships among the constituents of episodes. It has been proposed that this binding is automatic and obligatory during learning and remembering In addition, neuroimaging studies have highlighted the importance of the prefrontal cortex, in learning, memory, and language processing. However, the posited importance of hippocampal-prefrontal interaction remains to be empirically tested. In the present study we used functional magnetic resonance imaging to examine in detail this interaction by assessing learning-related changes in hemodynamic activity during artificial language acquisition. It has been shown previously that artificial grammar systems might be learned by evaluating pattern-based relations in word sequences and generalizing beyond specific word order, that is, rule abstraction. During scanning, participants learned an artificial language whose miniature grammar meets the universal principles of a natural language. Increased proficiency level of the artificial language is associated with decreased left hippocampal activity. In contrast, we observed an increased recruitment of the left inferior frontal gyrus (Broca's area), a region that contributes to syntax processing in natural language. The present results, therefore, indicate a learning-related change in brain circuitry underlying relational processes of language learning, with a transition from a similarity-based learning system in the medial temporal lobes to a language-related processing system in the left prefrontal cortex.

  10. Rostral and caudal prefrontal contribution to creativity: A meta-analysis of functional imaging data

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    Gil eGonen-Yaacovi

    2013-08-01

    Full Text Available Creativity is of central importance for human civilization, yet its neurocognitive bases are poorly understood. The aim of the present study was to integrate existing functional imaging data by using the meta-analysis approach. We reviewed 34 functional imaging studies that reported activation foci during tasks assumed to engage creative thinking in healthy adults. A coordinate-based meta-analysis using Activation Likelihood Estimation (ALE first showed a set of predominantly left-hemispheric regions shared by the various creativity tasks examined. These regions included the caudal lateral prefrontal cortex (PFC, the medial and lateral rostral PFC, and the inferior parietal and posterior temporal cortices. Further analyses showed that tasks involving the combination of remote information (combination tasks activated more anterior areas of the lateral PFC than tasks involving the free generation of unusual responses (unusual generation tasks, although both types of tasks shared caudal prefrontal areas. In addition, verbal and non-verbal tasks involved the same regions in the left caudal prefrontal, temporal, and parietal areas, but also distinct domain-oriented areas. Taken together, these findings suggest that several frontal and parieto-temporal regions may support cognitive processes shared by diverse creativity tasks, and that some regions may be specialized for distinct types of processes. In particular, the lateral PFC appeared to be organized along a rostro-caudal axis, with rostral regions involved in combining ideas creatively and more posterior regions involved in freely generating novel ideas.

  11. Acute Exercise Improves Prefrontal Cortex but not Hippocampal Function in Healthy Adults.

    Science.gov (United States)

    Basso, Julia C; Shang, Andrea; Elman, Meredith; Karmouta, Ryan; Suzuki, Wendy A

    2015-11-01

    The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise.

  12. Food seeking in spite of harmful consequences is under prefrontal cortical noradrenergic control

    Directory of Open Access Journals (Sweden)

    Patrono Enrico

    2010-02-01

    Full Text Available Abstract Background Eating disorders are multifactorial psychiatric disorders. Chronic stressful experiences and caloric restriction are the most powerful triggers of eating disorders in human and animals. Although compulsive behavior is considered to characterize pathological excessive food intake, to our knowledge, no evidence has been reported of continued food seeking/intake despite its possible harmful consequences, an index of compulsive behavior. Brain monoamine transmission is considered to have a key role in vulnerability to eating disorders, and norepinephrine in medial prefrontal cortex has been shown to be critical for food-related motivated behavior. Here, using a new paradigm of conditioned suppression, we investigated whether the ability of a foot-shock-paired conditioned stimulus to suppress chocolate-seeking behavior was reversed by previous exposure to a food restriction experience, thus modeling food seeking in spite of harmful consequences in mice. Moreover, we assessed the effects of selective norepinephrine inactivation in medial prefrontal cortex on conditioned suppression test in stressed and caloric restricted mice. Results While Control (non food deprived animals showed a profound conditioned suppression of chocolate seeking during presentation of conditioned stimulus, previously food restricted animals showed food seeking/intake despite its possible harmful consequences. Moreover, food seeking in spite of harmful consequences was prevented by selective norepinephrine inactivation, thus showing that prefrontal cortical norepinephrine is critical also for maladaptive food-related behavior. Conclusions These findings indicate that adaptive food seeking/intake can be transformed into maladaptive behaviors and point to "top-down" influence on eating disturbances and to new targets for therapy of aberrant eating behaviors.

  13. Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala Inputs.

    Science.gov (United States)

    Tejeda, Hugo A; Hanks, Ashley N; Scott, Liam; Mejias-Aponte, Carlos; Hughes, Zoë A; O'Donnell, Patricio

    2015-12-01

    Kappa opioid receptors (KORs) have been implicated in anxiety and stress, conditions that involve activation of projections from the basolateral amygdala (BLA) to the medial prefrontal cortex (mPFC). Although KORs have been studied in several brain regions, their role on mPFC physiology and on BLA projections to the mPFC remains unclear. Here, we explored whether KORs modify synaptic inputs from the BLA to the mPFC using in vivo electrophysiological recordings with electrical and optogenetic stimulation. Systemic administration of the KOR agonist U69,593 inhibited BLA-evoked synaptic responses in the mPFC without altering hippocampus-evoked responses. Intra-mPFC U69,593 inhibited electrical and optogenetic BLA-evoked synaptic responses, an effect blocked by the KOR antagonist nor-BNI. Bilateral intra-mPFC injection of the KOR antagonist nor-BNI increased center time in the open field test, suggesting an anxiolytic effect. The data demonstrate that mPFC KORs negatively regulate glutamatergic synaptic transmission in the BLA-mPFC pathway and anxiety-like behavior. These findings provide a framework whereby KOR signaling during stress and anxiety can regulate the flow of emotional state information from the BLA to the mPFC.

  14. Prefrontal contributions to relational encoding in amnestic mild cognitive impairment

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    Chris M. Foster

    2016-01-01

    Full Text Available Relational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI. Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies using functional magnetic resonance imaging (fMRI have primarily focused on binding deficits which are thought to be mediated by medial temporal lobe dysfunction. In this study, prefrontal contributions to relational encoding were also investigated using fMRI by parametrically manipulating generation demands during the encoding of word triads. Participants diagnosed with aMCI and healthy control subjects encoded word triads consisting of a category word with either, zero, one, or two semantically related exemplars. As the need to generate increased (i.e., two- to one- to zero-link triads, both groups recruited a core set of regions associated with the encoding of word triads including the parahippocampal gyrus, superior temporal gyrus, and superior parietal lobule. Participants diagnosed with aMCI also parametrically recruited several frontal regions including the inferior frontal gyrus and middle frontal gyrus as the need to generate increased, whereas the control participants did not show this modulation. While there is some functional overlap in regions recruited by generation demands between the groups, the recruitment of frontal regions in the aMCI participants coincides with worse memory performance, likely representing a form of neural inefficiency associated with Alzheimer's disease.

  15. Prefrontal contributions to relational encoding in amnestic mild cognitive impairment.

    Science.gov (United States)

    Foster, Chris M; Addis, Donna Rose; Ford, Jaclyn H; Kaufer, Daniel I; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A; Giovanello, Kelly S

    2016-01-01

    Relational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI). Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies using functional magnetic resonance imaging (fMRI) have primarily focused on binding deficits which are thought to be mediated by medial temporal lobe dysfunction. In this study, prefrontal contributions to relational encoding were also investigated using fMRI by parametrically manipulating generation demands during the encoding of word triads. Participants diagnosed with aMCI and healthy control subjects encoded word triads consisting of a category word with either, zero, one, or two semantically related exemplars. As the need to generate increased (i.e., two- to one- to zero-link triads), both groups recruited a core set of regions associated with the encoding of word triads including the parahippocampal gyrus, superior temporal gyrus, and superior parietal lobule. Participants diagnosed with aMCI also parametrically recruited several frontal regions including the inferior frontal gyrus and middle frontal gyrus as the need to generate increased, whereas the control participants did not show this modulation. While there is some functional overlap in regions recruited by generation demands between the groups, the recruitment of frontal regions in the aMCI participants coincides with worse memory performance, likely representing a form of neural inefficiency associated with Alzheimer's disease.

  16. Affective ambiguity for a group recruits ventromedial prefrontal cortex.

    Science.gov (United States)

    Simmons, Alan; Stein, Murray B; Matthews, Scott C; Feinstein, Justin S; Paulus, Martin P

    2006-01-15

    Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces.

  17. Prefrontal-amygdala fear networks come into focus

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    Maithe eArruda-Carvalho

    2015-10-01

    Full Text Available The ability to form associations between aversive threats and their predictors is fundamental to survival. However, fear and anxiety in excess are detrimental and are a hallmark of psychiatric diseases such as post-traumatic stress disorder (PTSD. PTSD symptomatology includes persistent and intrusive thoughts of an experienced trauma, suggesting an inability to downregulate fear when a corresponding threat has subsided. Convergent evidence from human and rodent studies supports a role for the medial prefrontal cortex (mPFC-amygdala network in both PTSD and the regulation of fear memory expression. In particular, current models stipulate that the prelimbic and infralimbic subdivisions of the rodent mPFC bidirectionally regulate fear expression via differential recruitment of amygdala neuronal subpopulations. However, an array of recent studies that employ new technical approaches has fundamentally challenged this interpretation. Here we explore how a new emphasis on the contribution of inhibitory neuronal populations, subcortical structures and the passage of time is reshaping our understanding of mPFC-amygdala circuits and their control over fear.

  18. Working Memory in the Prefrontal Cortex

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    Shintaro Funahashi

    2017-04-01

    Full Text Available The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified.

  19. [Tibial periostitis ("medial tibial stress syndrome")].

    Science.gov (United States)

    Fournier, Pierre-Etienne

    2003-06-01

    Medial tibial stress syndrome is characterised by complaints along the posteromedial tibia. Runners and athletes involved in jumping activities may develop this syndrome. Increased stress to stabilize the foot especially when excessive pronation is present explain the occurrence this lesion.

  20. Medial and Lateral Plantar Nerve Entrapment

    Science.gov (United States)

    ... Foot Problems Overview of Foot Problems Achilles Tendon Bursitis Achilles Tendon Enthesopathy Bunion Corns and Calluses Damage ... the Foot Freiberg Disease Hammer Toe Inferior Calcaneal Bursitis Medial and Lateral Plantar Nerve Entrapment Metatarsal Joint ...

  1. Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action

    OpenAIRE

    Mocci, Giuseppe; Jiménez-Sánchez, Laura; Adell, Albert; Cortés, Roser; Artigas, Francesc

    2013-01-01

    The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially target cortical serotonin (5-HT) receptors. The brain networks involved in the therapeutic action of atypical drugs are not fully understood. Previous work indicated that medial PFC (mPFC) pyramidal neur...

  2. UMAPRM: Uniformly sampling the medial axis

    KAUST Repository

    Yeh, Hsin-Yi Cindy

    2014-05-01

    © 2014 IEEE. Maintaining clearance, or distance from obstacles, is a vital component of successful motion planning algorithms. Maintaining high clearance often creates safer paths for robots. Contemporary sampling-based planning algorithms That utilize The medial axis, or The set of all points equidistant To Two or more obstacles, produce higher clearance paths. However, They are biased heavily Toward certain portions of The medial axis, sometimes ignoring parts critical To planning, e.g., specific Types of narrow passages. We introduce Uniform Medial Axis Probabilistic RoadMap (UMAPRM), a novel planning variant That generates samples uniformly on The medial axis of The free portion of Cspace. We Theoretically analyze The distribution generated by UMAPRM and show its uniformity. Our results show That UMAPRM\\'s distribution of samples along The medial axis is not only uniform but also preferable To other medial axis samplers in certain planning problems. We demonstrate That UMAPRM has negligible computational overhead over other sampling Techniques and can solve problems The others could not, e.g., a bug Trap. Finally, we demonstrate UMAPRM successfully generates higher clearance paths in The examples.

  3. Discusión de modelos para la corteza y manto superior en la zona Sur del área Centroibérica, basados en anomalías gravimétricas

    Directory of Open Access Journals (Sweden)

    Bergamín, J. F.

    1986-06-01

    Full Text Available With the porpuse of realize an interpretation in deep of the Campo de Calatrava vulcanism origin, it is done a gravimetric porfile, making various two-dimensional models of the Crust and Upper Mantle. Lately we discussed differents compatible posibilites with the existence of such volcanism.

    Con el fin de realizar una interpretación en profundidad del origen del vulcanismo de Campo de Calatrava, se efectúa un perfil gravimétrico, elaborándose varios modelos bidimensionales de Corteza y Manto superior. Posteriormente se discuten las distintas posibilidades compatibles con la existencia del citado vulcanismo.

  4. Eficiencia de los extractos hexánico, etanólico y metanólico de la corteza de Tabebuia serratifolia (tahuari) en Rattus norvegicus (rata albina) como hipoglucemiante en ratas hiperglicémicas

    OpenAIRE

    Suarez Rumiche, Jorge Antonio

    2014-01-01

    Ing. Grandez Ruíz, Maritza, Dra. El presente trabajo se desarrolló en el laboratorio de Química Analítica de la Universidad nacional de la Amazonía Peruana y en el Instituto de Medicina Tradicional (IMET) de la Ciudad de Iquitos - Perú. Se evaluó la eficiencia de los extractos hexánico, etanólico y metanólico de la corteza de Tabebuia serratifolia (Tahuarí) como hipoglucemiante en ratas hiperglicémicas. El ensayo se realizó en 35 ratas albinas Ratus norvegicus cepa Holtzman, machos de apro...

  5. Caracterización de los efectos de la administración de la lectina antinutricional nigrina de corteza de Sambucus nigra L. y efecto sinérgico con los polifenoles del té verde

    OpenAIRE

    Cabrero Lobato, Patricia

    2012-01-01

    Las proteínas inactivadoras de ribosomas (RIPs) son enzimas con actividad N-glicosidasa del ARN ribosómico. Algunas poseen dos cadenas una con actividad enzimática y otra con actividad lectina (RIPs de tipo dos). Entre estas RIPs se encuentra la nigrina b presente en la corteza de Sambucus nigra L. La nigrina b presenta toxicidad selectiva en función de la dosis y la vía de administración. El blanco son las células de las criptas del intestino delgado. Nuestra hipótesis es que los efectos tóx...

  6. Acute stress effects on GABA and glutamate levels in the prefrontal cortex: A 7T (1)H magnetic resonance spectroscopy study.

    Science.gov (United States)

    Houtepen, L C; Schür, R R; Wijnen, J P; Boer, V O; Boks, M P M; Kahn, R S; Joëls, M; Klomp, D W; Vinkers, C H

    2017-01-01

    There is ample evidence that the inhibitory GABA and the excitatory glutamate system are essential for an adequate response to stress. Both GABAergic and glutamatergic brain circuits modulate hypothalamus-pituitary-adrenal (HPA)-axis activity, and stress in turn affects glutamate and GABA levels in the rodent brain. However, studies examining stress-induced GABA and glutamate levels in the human brain are scarce. Therefore, we investigated the influence of acute psychosocial stress (using the Trier Social Stress Test) on glutamate and GABA levels in the medial prefrontal cortex of 29 healthy male individuals using 7 Tesla proton magnetic resonance spectroscopy. In vivo GABA and glutamate levels were measured before and 30 min after exposure to either the stress or the control condition. We found no associations between psychosocial stress or cortisol stress reactivity and changes over time in medial prefrontal glutamate and GABA levels. GABA and glutamate levels over time were significantly correlated in the control condition but not in the stress condition, suggesting that very subtle differential effects of stress on GABA and glutamate across individuals may occur. However, overall, acute psychosocial stress does not appear to affect in vivo medial prefrontal GABA and glutamate levels, at least this is not detectable with current practice (1)H-MRS.

  7. Sensitive Dependence of Mental Function on Prefrontal Cortex

    OpenAIRE

    Alen J Salerian

    2015-01-01

    This study offers evidence to suggest that both normalcy and psychiatric illness are sensitively dependent upon prefrontal cortex function. In general, the emergence of psychiatric symptoms coincide with diminished influence of prefrontal cortex function. The mediating influence of prefrontal cortex may be independent of molecular and regional brain dysfunctions contributory to psychiatric illness.

  8. Efecto de la infección por el virus de la rabia sobre la expresión de parvoalbúmina, calbindina y calretinina en la corteza cerebral de ratones.

    Directory of Open Access Journals (Sweden)

    Orlando Torres-Fernández

    2004-03-01

    Full Text Available Algunas manifestaciones clínicas de la rabia, así como los resultados de experimentos con cultivos celulares y animales de laboratorio han llevado a sugerir que el virus de la rabia afecta la neurotransmisión gabaérgica. En la corteza cerebral existen diferentes tipos de neuronas que sintetizan el neurotransmisor GABA. Éstas se pueden identificar con marcadores neuronales, entre los que se destacan tres proteínas ligadoras de calcio: la parvoalbúmina (PV, la calbindina (CB y la calretinina (CR. El virus de la rabia se disemina a través de la corteza cerebral pero se desconocen sus posibles efectos citopáticos sobre las neuronas gabaérgicas. Para evaluar el efecto de la rabia sobre estas neuronas, se estudió mediante inmunohistoquímica la expresión de PV, CB y CR en la corteza frontal de ratones normales y ratones infectados con virus 'calle' o virus 'fijo' de la rabia. La PV se expresó en neuronas multipolares dispersas regularmente entre las capas II y VI, y en botones sinápticos que bordeaban el soma de las neuronas piramidales. La inmunorreactividad a CB se manifestó en dos franjas corticales: la primera, en las capas supragranulares II y III en neuronas con somas redondeados e inmersos en un neuropilo intensamente marcado; la segunda, en las capas infragranulares V y VI en neuronas multipolares dispersas y rodeadas por un neuropilo menos reactivo. La CR se expresó en neuronas bipolares con somas fusiformes distribuidas en las seis capas corticales, pero concentradas principalmente en las capas II y III. Hubo una característica común en las muestras infectadas con los dos tipos de virus: la inmunotinción a PV fue más intensa que en las muestras normales. La infección derivada del virus 'calle' no causó alteraciones adicionales en la expresión de las tres proteínas. En contraste, la infección con virus 'fijo' produjo una reducción notable del número de neuronas CB+, así como de la inmunorreactividad a CB en el

  9. Medial meniscal cyst: a case report.

    Science.gov (United States)

    Spina, Mauro; Sabbioni, Giacomo; Tigani, Domenico

    2008-12-01

    Meniscal cysts are a rare disease constantly combined with a horizontal meniscal lesion. Currently, nuclear magnetic resonance (MRI) is the main diagnostic tool, because of its high sensitivity and specificity, and decompression arthroscopy combined with selective meniscectomy is the treatment of choice. The Authors report a case of a voluminous medial meniscal cyst where instrumental examination, MRI, was fundamental for the preoperative diagnosis of the horizontal meniscal lesion causing the cystic degeneration of the meniscus. The treatment performed was selective meniscectomy of the body and posterior horn of the medial meniscus and decompression of the voluminous cyst by arthroscopy. Physical examination after six months showed the complete resolution of swelling at the medial hemirima, no walking pain and normal range of motion.

  10. Neural modeling of prefrontal executive function

    Energy Technology Data Exchange (ETDEWEB)

    Levine, D.S. [Univ. of Texas, Arlington, TX (United States)

    1996-12-31

    Brain executive function is based in a distributed system whereby prefrontal cortex is interconnected with other cortical. and subcortical loci. Executive function is divided roughly into three interacting parts: affective guidance of responses; linkage among working memory representations; and forming complex behavioral schemata. Neural network models of each of these parts are reviewed and fit into a preliminary theoretical framework.

  11. Human prefrontal cortex: evolution, development, and pathology.

    Science.gov (United States)

    Teffer, Kate; Semendeferi, Katerina

    2012-01-01

    The prefrontal cortex is critical to many cognitive abilities that are considered particularly human, and forms a large part of a neural system crucial for normal socio-emotional and executive functioning in humans and other primates. In this chapter, we survey the literature regarding prefrontal development and pathology in humans as well as comparative studies of the region in humans and closely related primate species. The prefrontal cortex matures later in development than more caudal regions, and some of its neuronal subpopulations exhibit more complex dendritic arborizations. Comparative work suggests that the human prefrontal cortex differs from that of closely related primate species less in relative size than it does in organization. Specific reorganizational events in neural circuitry may have taken place either as a consequence of adjusting to increases in size or as adaptive responses to specific selection pressures. Living in complex environments has been recognized as a considerable factor in the evolution of primate cognition. Normal frontal lobe development and function are also compromised in several neurological and psychiatric disorders. A phylogenetically recent reorganization of frontal cortical circuitry may have been critical to the emergence of human-specific executive and social-emotional functions, and developmental pathology in these same systems underlies many psychiatric and neurological disorders, including autism and schizophrenia.

  12. Stress Assessment by Prefrontal Relative Gamma

    Science.gov (United States)

    Minguillon, Jesus; Lopez-Gordo, Miguel A.; Pelayo, Francisco

    2016-01-01

    Stress assessment has been under study in the last years. Both biochemical and physiological markers have been used to measure stress level. In neuroscience, several studies have related modification of stress level to brain activity changes in limbic system and frontal regions, by using non-invasive techniques such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). In particular, previous studies suggested that the exhibition or inhibition of certain brain rhythms in frontal cortical areas indicates stress. However, there is no established marker to measure stress level by EEG. In this work, we aimed to prove the usefulness of the prefrontal relative gamma power (RG) for stress assessment. We conducted a study based on stress and relaxation periods. Six healthy subjects performed the Montreal Imaging Stress Task (MIST) followed by a stay within a relaxation room while EEG and electrocardiographic signals were recorded. Our results showed that the prefrontal RG correlated with the expected stress level and with the heart rate (HR; 0.8). In addition, the difference in prefrontal RG between time periods of different stress level was statistically significant (p < 0.01). Moreover, the RG was more discriminative between stress levels than alpha asymmetry, theta, alpha, beta, and gamma power in prefrontal cortex. We propose the prefrontal RG as a marker for stress assessment. Compared with other established markers such as the HR or the cortisol, it has higher temporal resolution. Additionally, it needs few electrodes located at non-hairy head positions, thus facilitating the use of non-invasive dry wearable real-time devices for ubiquitous assessment of stress. PMID:27713698

  13. The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults.

    Science.gov (United States)

    Wilckens, Kristine A; Aizenstein, Howard J; Nofzinger, Eric A; James, Jeffrey A; Hasler, Brant P; Rosario-Rivera, Bedda L; Franzen, Peter L; Germain, Anne; Hall, Martica H; Kupfer, David J; Price, Julie C; Siegle, Greg J; Buysse, Daniel J

    2016-06-01

    Electroencephalographic slow-wave activity (0.5-4 Hz) during non-rapid eye movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow wave activity during sleep may promote greater waking prefrontal metabolic rate and, in turn, executive function. However, this process may be affected by age. Here we examined whether greater NREM slow wave activity was associated with higher prefrontal metabolism during wakefulness and whether this relationship interacted with age. Fifty-two participants aged 25-61 years were enrolled into studies that included polysomnography and a (18) [F]-fluoro-deoxy-glucose positron emission tomography scan during wakefulness. Absolute and relative measures of NREM slow wave activity were assessed. Semiquantitative and relative measures of cerebral metabolism were collected to assess whole brain and regional metabolism, focusing on two regions of interest: the dorsolateral prefrontal cortex and the orbitofrontal cortex. Greater relative slow wave activity was associated with greater dorsolateral prefrontal metabolism. Age and slow wave activity interacted significantly in predicting semiquantitative whole brain metabolism and outside regions of interest in the posterior cingulate, middle temporal gyrus and the medial frontal gyrus, such that greater slow-wave activity was associated with lower metabolism in the younger participants and greater metabolism in the older participants. These results suggest that slow-wave activity is associated with cerebral metabolism during wakefulness across the adult lifespan within regions important for executive function.

  14. Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex.

    Science.gov (United States)

    Di Liberto, Valentina; Frinchi, Monica; Verdi, Vincenzo; Vitale, Angela; Plescia, Fulvio; Cannizzaro, Carla; Massenti, Maria F; Belluardo, Natale; Mudò, Giuseppa

    2017-02-01

    In depressive disorders, one of the mechanisms proposed for antidepressant drugs is the enhancement of synaptic plasticity in the hippocampus and cerebral cortex. Previously, we showed that the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine (Oxo) increases neuronal plasticity in hippocampal neurons via FGFR1 transactivation. Here, we aimed to explore (a) whether Oxo exerts anxiolytic effect in the rat model of anxiety-depression-like behavior induced by chronic restraint stress (CRS), and (b) if the anxiolytic effect of Oxo is associated with the modulation of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF2), and phosphorylated Erk1/2 (p-Erk1/2) levels in the dorsal or ventral hippocampus and in the medial prefrontal cortex. The rats were randomly divided into four groups: control unstressed, CRS group, CRS group treated with 0.2 mg/kg Oxo, and unstressed group treated with Oxo. After 21 days of CRS, the groups were treated for 10 days with Oxo or saline. The anxiolytic role of Oxo was tested by using the following: forced swimming test, novelty suppressed feeding test, elevated plus maze test, and light/dark box test. The hippocampi and prefrontal cortex were used to evaluate BDNF and FGF2 protein levels and p-Erk1/2 levels. Oxo treatment significantly attenuated anxiety induced by CRS. Moreover, Oxo treatment counteracted the CRS-induced reduction of BDNF and FGF2 levels in the ventral hippocampus and medial prefrontal cerebral cortex CONCLUSIONS: The present study showed that Oxo treatment ameliorates the stress-induced anxiety-like behavior and rescues FGF2 and BDNF levels in two brain regions involved in CRS-induced anxiety, ventral hippocampal formation, and medial prefrontal cortex.

  15. Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Ya-Ting Chang

    Full Text Available Amyloid deposition and white matter lesions (WMLs in Alzheimer's disease (AD are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden.Thirty patients with AD were enrolled, and AV-45 positron emission tomography was conducted to measure the regional standardized uptake value ratio (SUVr in 8 cortical volumes-of- interests (VOIs. The quantitative WMLs burden was measured from magnetic resonance imaging while the normalized VOIs volumes represented BR in this study. The cognitive test represented major clinical correlates.Significant correlations between the prefrontal volume and global (r = 0.470, p = 0.024, but not regional (r = 0.264, p = 0.223 AV-45 SUVr were found. AD patients having larger regional volume in the superior- (r = 0.572, p = 0.004, superior medial- (r = 0.443, p = 0.034, and middle-prefrontal (r = 0.448, p = 0.032 regions had higher global AV-45 SUVr. For global WML loads, the prefrontal (r = -0.458, p = 0.019 and hippocampal volume (r = -0.469, p = 0.016 showed significant correlations while the prefrontal (r = -0.417, p = 0.043 or hippocampal volume (r = -0.422, p = 0.04 also predicted better composite memory scores. There were no interactions between amyloid SUVr and WML loads on the prefrontal volume.BR of the prefrontal region might modulate the adverse global pathological burden caused by amyloid deposition. While prefrontal volume positively associated with hippocampal volume, WMLs had an adverse impact on the hippocampal volume that predicts memory performance in mild stage AD.

  16. Dissociable regulation of instrumental action within mouse prefrontal cortex.

    Science.gov (United States)

    Gourley, Shannon L; Lee, Anni S; Howell, Jessica L; Pittenger, Christopher; Taylor, Jane R

    2010-11-01

    Evaluation of the behavioral 'costs', such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal-directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal-directed and choice behavior, but this region's functional significance in rodents is unknown despite extensive work characterizing the role of the lateral OFC in cue-related response inhibition processes. We first tested mice with mOFC lesions in an instrumental reversal task lacking discrete cues signaling reinforcement; here, animals were required to shift responding based on the location of the reinforced aperture within the chamber. Mice with mOFC lesions acquired the reversal but failed to inhibit responding on the previously reinforced aperture, while mice with prelimbic prefrontal cortex lesions were unaffected. When tested on a progressive ratio schedule of reinforcement, mice with prelimbic cortical lesions were unable to maintain responding, resulting in declining response levels. Mice with mOFC lesions, by contrast, escalated responding. Neither lesion affected sensitivity to satiety-specific outcome devaluation or non-reinforcement (i.e. extinction), and neither had effects when placed after animals were trained on a progressive ratio response schedule. Lesions of the ventral hippocampus, which projects to the mOFC, resulted in similar response patterns, while lateral OFC and dorsal hippocampus lesions resulted in response acquisition, though not inhibition, deficits in an instrumental reversal. Our findings thus selectively implicate the rodent mOFC in braking reinforced goal-directed action when reinforcement requires the acquisition of novel response contingencies.

  17. Medial branch neurotomy in low back pain

    Energy Technology Data Exchange (ETDEWEB)

    Masala, Salvatore; Mammucari, Matteo; Simonetti, Giovanni [Interventional Radiology and Radiotherapy University ' ' Tor Vergata' ' , Department of Diagnostic and Molecular Imaging, Rome (Italy); Nano, Giovanni [Interventional Radiology and Radiotherapy University ' ' Tor Vergata' ' , Department of Diagnostic and Molecular Imaging, Rome (Italy); University ' ' Tor Vergata' ' , Department of Radiology, Rome (Italy); Marcia, Stefano [S. Giovanni di Dio Hospital, Department of Diagnostic and Molecular Imaging, Cagliari (Italy)

    2012-07-15

    This study aimed to assess the effectiveness of pulsed radiofrequency medial branch dorsal ramus neurotomy in patients with facet joint syndrome. From January 2008 to April 2010, 92 patients with facet joint syndrome diagnosed by strict inclusion criteria and controlled diagnostic blocks undergone medial branch neurotomy. We did not exclude patients with failed back surgery syndrome (FBSS). Electrodes (20G) with 5-mm active tip were placed under fluoroscopy guide parallel to medial branch. Patients were followed up by physical examination and by Visual Analog Scale and Oswestry Disability Index at 1, 6, and 12 months. In all cases, pain improvement was statistically significant and so quality of life. Three non-FBSS patients had to undergo a second neurotomy because of non-satisfactory pain decrease. Complications were reported in no case. Medial branch radiofrequency neurotomy has confirmed its well-established effectiveness in pain and quality of life improvement as long as strict inclusion criteria be fulfilled and nerve ablation be accomplished by parallel electrode positioning. This statement can be extended also to FBSS patients. (orig.)

  18. [Arthritis of the Medial Knee Joint Compartment].

    Science.gov (United States)

    Matziolis, G; Röhner, E

    2015-10-01

    23 % of all persons older than 65 years suffer from osteoarthritis of the medial compartment of the knee joint, a very common situation in orthopaedic practice 1. As a result of the demographic trend the number of patients is expected to increase in the future. Based on specific joint biomechanics and kinematics the medial knee joint compartment is more frequently affected than the lateral. Only an understanding of the functional anatomy and underlying pathology allows a critical evaluation of different available conservative and operative treatment options. This article gives an overview of diagnostic and therapeutic strategies of osteoarthritis of the medial knee joint. Frequently performed surgeries, e.g. high tibial osteotomy (HTO), unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) will be presented in a comparative manner. The actual scientific evidence will be given with the goal of an evidence based therapy that is adopted to stage and pathology of osteoarthritis of the medial compartment of the knee joint. Georg Thieme Verlag KG Stuttgart · New York.

  19. Rheo: Japanese Sound Art Interrogating Digital Mediality

    DEFF Research Database (Denmark)

    Vandsø, Anette

    2014-01-01

    THe article asks in what way the Japanese sound artist Ryoichi Kurokawa's audiovisual installation Rheo 5 Horisonz (2010) is 'digital'. Using Professor Lars Elleströms concept of 'mediality, the main claim in this article is that Rheo no only uses digital tehcnology, but also interrogates digital...

  20. Extinction of fear is facilitated by social presence: Synergism with prefrontal oxytocin.

    Science.gov (United States)

    Brill-Maoz, Naama; Maroun, Mouna

    2016-04-01

    This study addressed the question of whether extinction in pairs would have a beneficial effect on extinction of fear conditioning. To that end, we established an experimental setting for extinction in which we trained animals to extinguish contextual fear memory in pairs. Taking advantage of the role of oxytocin (OT) in the medial prefrontal cortex (mPFC) in the mediation of memory extinction and social interaction, we also sought to study its role in social interaction-induced effects on extinction. Our results clearly show that the social presence of another animal in the extinction context facilitates extinction, and that this facilitation is mediated through mPFC-OT. Our results suggest that social interaction may be a positive regulator of fear inhibition, implying that social interaction may be an easy, accessible therapeutic tool for the treatment of fear-associated disorders.

  1. Disruption of prefrontal cortical-hippocampal balance in a developmental model of schizophrenia: reversal by sulpiride.

    Science.gov (United States)

    Belujon, Pauline; Patton, Mary H; Grace, Anthony A

    2013-04-01

    The nucleus accumbens (NAc) receives converging inputs from the medial prefrontal cortex (mPFC) and the hippocampus which have competitive interactions in the NAc to influence motivational drive. We have previously shown altered synaptic plasticity in the hippocampal-NAc pathway in the methylazoxymethanol acetate (MAM) developmental model of schizophrenia in rodents that is dependent on cortical inputs. Thus, because mPFC-hippocampal balance is known to be partially altered in this model, we investigated potential pathological changes in the hippocampal influence over cortex-driven NAc spike activity. Here we show that the reciprocal interaction between the hippocampus and mPFC is absent in MAM animals but is able to be reinstated with administration of the antipsychotic drug, sulpiride. The lack of interaction between these structures in this model could explain the attentional deficits in schizophrenia patients and shed light onto their inability to focus on a single task.

  2. Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala.

    Science.gov (United States)

    Pleil, Kristen E; Lowery-Gionta, Emily G; Crowley, Nicole A; Li, Chia; Marcinkiewcz, Catherine A; Rose, Jamie H; McCall, Nora M; Maldonado-Devincci, Antoniette M; Morrow, A Leslie; Jones, Sara R; Kash, Thomas L

    2015-12-01

    Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (lCeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry.

  3. The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory.

    Science.gov (United States)

    Hales, J B; Brewer, J B

    2011-04-01

    The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance.

  4. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation?

    Energy Technology Data Exchange (ETDEWEB)

    Guedj, Eric [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille Cedex 5 (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR CNRS 6612, Faculte de Medecine, Marseille (France); Barbeau, Emmanuel J. [CNRS - Universite Paul Sabatier Toulouse 3, Centre de Recherche Cerveau et Cognition, UMR-5549, Toulouse (France); Didic, Mira; Poncet, Michel; Ceccaldi, Mathieu [CHU Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Felician, Olivier [CHU Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Centre Saint-Charles, Laboratoire de Neurobiologie Integrative et Adaptative, UMR CNRS 6149, Marseille (France); Laforte, Catherine de; Mundler, Olivier [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille Cedex 5 (France); Ranjeva, Jean-Philippe; Cozzone, Patrick J. [Universite de la Mediterranee Aix-Marseille II, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR CNRS 6612, Faculte de Medecine, Marseille (France)

    2009-07-15

    Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the ''net sum'' of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective. (orig.)

  5. Hyperglycemia decreased medial amygdala projections to medial preoptic area in experimental model of Diabetes Mellitus.

    OpenAIRE

    Yousef Mohamadi; Seyed Behnam-edin Jameie; Mohammad Akbari; Masumeh Staji; Fatemeh Moradi; Tahmineh Mokhtari; Maryam Khanehzad; Gholamreza Hassanzadeh

    2015-01-01

    In Wistar rats, reproductive behavior is controlled in a neural circuit of ventral forebrain including the medial amygdala (Me), bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA) via perception of social odors. Diabetes Mellitus (DM) is a widespread metabolic disease that affects many organs in a variety of levels. DM can cause central neuropathies such as neuronal apoptosis, dendritic atrophy, neurochemical alterations and also causes reproductive dysfunctions. So we...

  6. Capacity-speed relationships in prefrontal cortex.

    Science.gov (United States)

    Prabhakaran, Vivek; Rypma, Bart; Narayanan, Nandakumar S; Meier, Timothy B; Austin, Benjamin P; Nair, Veena A; Naing, Lin; Thomas, Lisa E; Gabrieli, John D E

    2011-01-01

    Working memory (WM) capacity and WM processing speed are simple cognitive measures that underlie human performance in complex processes such as reasoning and language comprehension. These cognitive measures have shown to be interrelated in behavioral studies, yet the neural mechanism behind this interdependence has not been elucidated. We have carried out two functional MRI studies to separately identify brain regions involved in capacity and speed. Experiment 1, using a block-design WM verbal task, identified increased WM capacity with increased activity in right prefrontal regions, and Experiment 2, using a single-trial WM verbal task, identified increased WM processing speed with increased activity in similar regions. Our results suggest that right prefrontal areas may be a common region interlinking these two cognitive measures. Moreover, an overlap analysis with regions associated with binding or chunking suggest that this strategic memory consolidation process may be the mechanism interlinking WM capacity and WM speed.

  7. Capacity-speed relationships in prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Vivek Prabhakaran

    Full Text Available Working memory (WM capacity and WM processing speed are simple cognitive measures that underlie human performance in complex processes such as reasoning and language comprehension. These cognitive measures have shown to be interrelated in behavioral studies, yet the neural mechanism behind this interdependence has not been elucidated. We have carried out two functional MRI studies to separately identify brain regions involved in capacity and speed. Experiment 1, using a block-design WM verbal task, identified increased WM capacity with increased activity in right prefrontal regions, and Experiment 2, using a single-trial WM verbal task, identified increased WM processing speed with increased activity in similar regions. Our results suggest that right prefrontal areas may be a common region interlinking these two cognitive measures. Moreover, an overlap analysis with regions associated with binding or chunking suggest that this strategic memory consolidation process may be the mechanism interlinking WM capacity and WM speed.

  8. The prefrontal dysfunction in individuals with Internet gaming disorder: a meta-analysis of functional magnetic resonance imaging studies.

    Science.gov (United States)

    Meng, Yajing; Deng, Wei; Wang, Huiyao; Guo, Wanjun; Li, Tao

    2015-07-01

    With the advancement in high-resolution magnetic resonance imaging (MRI) technology and automated analysis, studies on functional MRI (fMRI) made it possible to identify the functional activity of brain in vivo in individuals with Internet gaming disorder (IGD), and to explore the underpinning neuroscience basis of IGD. Yet, no available literature has systemically reviewed the fMRI studies of IGD using meta-analyses. This study reviewed 61 candidate articles and finally selected 10 qualified voxel-wise whole-brain analysis studies for performing a comprehensive series of meta-analyses employing effect size signed differential mapping approach. Compared with healthy controls, subjects with IGD showed a significant activation in the bilateral medial frontal gyrus (MFG) and the left cingulate gyrus, as well as the left medial temporal gyrus and fusiform gyrus. Furthermore, the on-line time of IGD subjects was positively correlated with activations in the left MFG and the right cingulated gyrus. These findings implicate the important role of dysfunctional prefrontal lobe in the neuropathological mechanism of IGD. Considering the overlapped role of prefrontal lobe in the reward and self-regulatory system, our results provided supportive evidence for the reclassification of IGD as a behavioural addiction.

  9. Early social experience is critical for the development of cognitive control and dopamine modulation of prefrontal cortex function.

    Science.gov (United States)

    Baarendse, Petra J J; Counotte, Danielle S; O'Donnell, Patricio; Vanderschuren, Louk J M J

    2013-07-01

    Social experiences during youth are thought to be critical for proper social and cognitive development. Conversely, social insults during development can cause long-lasting behavioral impairments and increase the vulnerability for psychopathology later in life. To investigate the importance of social experience during the juvenile and early adolescent stage for the development of cognitive control capacities, rats were socially isolated from postnatal day 21 to 42 followed by re-socialization until they reached adulthood. Subsequently, two behavioral dimensions of impulsivity (impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task) and decision making (in the rat gambling task) were assessed. In a separate group of animals, long-lasting cellular and synaptic changes in adult medial prefrontal cortex (PFC) pyramidal neurons were determined following social isolation. Juvenile and early adolescent social isolation resulted in impairments in impulsive action and decision making under novel or challenging circumstances. Moreover, socially isolated rats had a reduced response to enhancement of dopaminergic neurotransmission (using amphetamine or GBR12909) in the 5-CSRTT under challenging conditions. Impulsive choice was not affected by social isolation. These behavioral deficits were accompanied by a loss of sensitivity to dopamine of pyramidal neurons in the medial PFC. Our data show long-lasting deleterious effects of early social isolation on cognitive control and its neural substrates. Alterations in prefrontal cognitive control mechanisms may contribute to the enhanced risk for psychiatric disorders induced by aberrations in the early social environment.

  10. The role of prefrontal cortex in psychopathy

    OpenAIRE

    Koenigs, Michael

    2012-01-01

    Psychopathy is a personality disorder characterized by remorseless and impulsive antisocial behavior. Given the significant societal costs of the recidivistic criminal activity associated with the disorder, there is a pressing need for more effective treatment strategies, and hence, a better understanding of the psychobiological mechanisms underlying the disorder. The prefrontal cortex (PFC) is likely to play an important role in psychopathy. In particular, the ventromedial and anterior cingu...

  11. Development of abstract thinking during childhood and adolescence: The role of rostrolateral prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Iroise Dumontheil

    2014-10-01

    Full Text Available Rostral prefrontal cortex (RPFC has increased in size and changed in terms of its cellular organisation during primate evolution. In parallel emerged the ability to detach oneself from the immediate environment to process abstract thoughts and solve problems and to understand other individuals’ thoughts and intentions. Rostrolateral prefrontal cortex (RLPFC is thought to play an important role in supporting the integration of abstract, often self-generated, thoughts. Thoughts can be temporally abstract and relate to long term goals, or past or future events, or relationally abstract and focus on the relationships between representations rather than simple stimulus features. Behavioural studies have provided evidence of a prolonged development of the cognitive functions associated with RLPFC, in particular logical and relational reasoning, but also episodic memory retrieval and prospective memory. Functional and structural neuroimaging studies provide further support for a prolonged development of RLPFC during adolescence, with some evidence of increased specialisation of RLPFC activation for relational integration and aspects of episodic memory retrieval. Topics for future research will be discussed, such as the role of medial RPFC in processing abstract thoughts in the social domain, the possibility of training abstract thinking in the domain of reasoning, and links to education.

  12. Development of abstract thinking during childhood and adolescence: the role of rostrolateral prefrontal cortex.

    Science.gov (United States)

    Dumontheil, Iroise

    2014-10-01

    Rostral prefrontal cortex (RPFC) has increased in size and changed in terms of its cellular organisation during primate evolution. In parallel emerged the ability to detach oneself from the immediate environment to process abstract thoughts and solve problems and to understand other individuals' thoughts and intentions. Rostrolateral prefrontal cortex (RLPFC) is thought to play an important role in supporting the integration of abstract, often self-generated, thoughts. Thoughts can be temporally abstract and relate to long term goals, or past or future events, or relationally abstract and focus on the relationships between representations rather than simple stimulus features. Behavioural studies have provided evidence of a prolonged development of the cognitive functions associated with RLPFC, in particular logical and relational reasoning, but also episodic memory retrieval and prospective memory. Functional and structural neuroimaging studies provide further support for a prolonged development of RLPFC during adolescence, with some evidence of increased specialisation of RLPFC activation for relational integration and aspects of episodic memory retrieval. Topics for future research will be discussed, such as the role of medial RPFC in processing abstract thoughts in the social domain, the possibility of training abstract thinking in the domain of reasoning, and links to education.

  13. Methylphenidate and atomoxetine inhibit social play behavior through prefrontal and subcortical limbic mechanisms in rats.

    Science.gov (United States)

    Achterberg, E J Marijke; van Kerkhof, Linda W M; Damsteegt, Ruth; Trezza, Viviana; Vanderschuren, Louk J M J

    2015-01-07

    Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD.

  14. Longitudinal development of prefrontal function during early childhood.

    Science.gov (United States)

    Moriguchi, Yusuke; Hiraki, Kazuo

    2011-04-01

    This is a longitudinal study on development of prefrontal function in young children. Prefrontal areas have been observed to develop dramatically during early childhood. To elucidate this development, we gave children cognitive shifting tasks related to prefrontal function at 3 years of age (Time 1) and 4 years of age (Time 2). We then monitored developmental changes in behavioral performance and examined prefrontal activation using near infrared spectroscopy. We found that children showed better behavioral performance and significantly stronger inferior prefrontal activation at Time 2 than they did at Time 1. Moreover, we demonstrated individual differences in prefrontal activation for the same behavioral tasks. Children who performed better in tasks at Time 1 showed significant activation of the right inferior prefrontal regions at Time 1 and significant activation of the bilateral inferior prefrontal regions at Time 2. Children who showed poorer performance at Time 1 exhibited no significant inferior prefrontal activation at Time 1 but significant left inferior prefrontal activation at Time 2. These results indicate the importance of the longitudinal method to address the link between cognitive and neural development.

  15. Contrasting Effects of Medial and Lateral Orbitofrontal Cortex Lesions on Credit Assignment and Decision-Making in Humans.

    Science.gov (United States)

    Noonan, MaryAnn P; Chau, Bolton K H; Rushworth, Matthew F S; Fellows, Lesley K

    2017-07-19

    The orbitofrontal cortex is critical for goal-directed behavior. Recent work in macaques has suggested the lateral orbitofrontal cortex (lOFC) is relatively more concerned with assignment of credit for rewards to particular choices during value-guided learning, whereas the medial orbitofrontal cortex (often referred to as ventromedial prefrontal cortex in humans; vmPFC/mOFC) is involved in constraining the decision to the relevant options. We examined whether people with damage restricted to subregions of prefrontal cortex showed the patterns of impairment observed in prior investigations of the effects of lesions to homologous regions in macaques. Groups of patients with either lOFC (predominantly right hemisphere), mOFC/vmPFC, or dorsomedial prefrontal (DMF), and a comparison group of healthy age- and education-matched controls performed a probabilistic 3-choice decision-making task. We report anatomically specific patterns of impairment. We found that credit assignment, as indexed by the normal influence of contingent relationships between choice and reward, is reduced in lOFC patients compared with Controls and mOFC/vmPFC patients. Moreover, the effects of reward contingency on choice were similar for patients with lesions in DMF or mOFC/vmPFC, compared with Controls. By contrast, mOFC/vmPFC-lesioned patients made more stochastic choices than Controls when the decision was framed by valuable distracting alternatives, suggesting that value comparisons were no longer independent of irrelevant options. Once again, there was evidence of regional specialization: patients with lOFC lesions were unimpaired relative to Controls. As in macaques, human lOFC and mOFC/vmPFC are necessary for contingent learning and value-guided decision-making, respectively.SIGNIFICANCE STATEMENT The lateral and medial regions of the orbitofrontal cortex are cytoarchitectonically distinct and have different anatomical connections. Previous investigations in macaques have shown these

  16. Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions.

    Science.gov (United States)

    Perry, Jennifer L; Joseph, Jane E; Jiang, Yang; Zimmerman, Rick S; Kelly, Thomas H; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P; Bardo, Michael T

    2011-01-01

    Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals.

  17. Muscarinic and nicotinic modulation of thalamo-prefrontal cortex synaptic plasticity [corrected] in vivo.

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    Lezio Soares Bueno-Junior

    Full Text Available The mediodorsal nucleus of the thalamus (MD is a rich source of afferents to the medial prefrontal cortex (mPFC. Dysfunctions in the thalamo-prefrontal connections can impair networks implicated in working memory, some of which are affected in Alzheimer disease and schizophrenia. Considering the importance of the cholinergic system to cortical functioning, our study aimed to investigate the effects of global cholinergic activation of the brain on MD-mPFC synaptic plasticity by measuring the dynamics of long-term potentiation (LTP and depression (LTD in vivo. Therefore, rats received intraventricular injections either of the muscarinic agonist pilocarpine (PILO; 40 nmol/µL, the nicotinic agonist nicotine (NIC; 320 nmol/µL, or vehicle. The injections were administered prior to either thalamic high-frequency (HFS or low-frequency stimulation (LFS. Test pulses were applied to MD for 30 min during baseline and 240 min after HFS or LFS, while field postsynaptic potentials were recorded in the mPFC. The transient oscillatory effects of PILO and NIC were monitored through recording of thalamic and cortical local field potentials. Our results show that HFS did not affect mPFC responses in vehicle-injected rats, but induced a delayed-onset LTP with distinct effects when applied following PILO or NIC. Conversely, LFS induced a stable LTD in control subjects, but was unable to induce LTD when applied after PILO or NIC. Taken together, our findings show distinct modulatory effects of each cholinergic brain activation on MD-mPFC plasticity following HFS and LFS. The LTP-inducing action and long-lasting suppression of cortical LTD induced by PILO and NIC might implicate differential modulation of thalamo-prefrontal functions under low and high input drive.

  18. Verbal memory deficits are correlated with prefrontal hypometabolism in (18FDG PET of recreational MDMA users.

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    Oliver G Bosch

    Full Text Available INTRODUCTION: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy" is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu in recreational MDMA users. METHODS: Brain glucose metabolism in rest was assessed using 2-deoxy-2-((18Ffluoro-D-glucose positron emission tomography ((18FDG PET in 19 male recreational users of MDMA and 19 male drug-naïve controls. (18FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test. RESULTS: As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex. CONCLUSIONS: Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users

  19. Prefrontal Dopaminergic Mechanisms of Extinction in Adolescence Compared to Adulthood in Rats

    Science.gov (United States)

    Zbukvic, Isabel C.; Park, Chun Hui J.; Ganella, Despina E.; Lawrence, Andrew J.; Kim, Jee Hyun

    2017-01-01

    Adolescents with anxiety disorders attain poorer outcomes following extinction-based treatment compared to adults. Extinction deficit during adolescence has been identified to involve immaturity in the medial prefrontal cortex (mPFC). Findings from adult rodents suggest extinction involves dopamine signaling in the mPFC. This system changes dramatically during adolescence, but its role in adolescent extinction is unknown. Therefore, we investigated the role of prefrontal dopamine in extinction using Pavlovian fear conditioning in adolescent and adult rats. Using quantitative PCR (qPCR) analyses, we measured changes in dopamine receptor gene expression in the mPFC before and after extinction. We then enhanced dopamine 1 receptor (D1R) or dopamine 2 receptor (D2R) signaling in the infralimbic cortex (IL) of the mPFC using agonists at the time of extinction. Adolescent rats displayed a deficit in extinction retention compared to adults. Extinction induced a reduction in D1R compared to D2R gene expression in adolescent rats, whereas an increase of D1R compared to D2R gene expression was observed in adult rats. Acutely enhancing IL D1R signaling using SKF-81297 had no effect on extinction at either age. In contrast, acutely enhancing IL D2R signaling with quinpirole significantly enhanced long-term extinction in adolescents, and impaired within-session extinction in adults. Our results suggest a dissociated role for prefrontal dopamine in fear extinction during adolescence compared to adulthood. Findings highlight the dopamine system as a potential pharmacological target to improve extinction-based treatments for adolescents. PMID:28275342

  20. Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

    Science.gov (United States)

    Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

    2014-10-29

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism.

  1. Foot medial longitudinal-arch deformation during quiet standing and gait in subjects with medial tibial stress syndrome

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Boysen, Lisbeth; Haugaard, Stine

    2008-01-01

    ). There was no correlation between medial longitudinal-arch deformation during quiet standing and gait in either of the 2 groups (r .653). The subjects with medial tibial stress syndrome in this study demonstrated increased navicular drop and medial longitudinal-arch deformation during quiet standing......The objective of this study was to investigate (1) if subjects with medial tibial stress syndrome demonstrate increased navicular drop and medial longitudinal-arch deformation during quiet standing and gait compared with healthy subjects, and (2) the relationship between medial longitudinal......-arch deformation during quiet standing and gait. Thirty subjects aged 20 to 32 years were included (15 with medial tibial stress syndrome and 15 controls). Navicular drop and medial longitudinal-arch deformation were measured during quiet standing with neutral and loaded foot using a ruler and digital photography...

  2. Crude extracts of Drimys winteri bark to inhibit growth of Gaeumannomyces graminis var. tritici Inhibición del crecimiento de Gaeumannomyces graminis var. tritici empleando extractos obtenidos de corteza de Drimys winteri

    Directory of Open Access Journals (Sweden)

    Nelson Zapata

    2011-03-01

    Full Text Available The aim of this study was to assess the effect of Drimys winteri J.R. Forst. & G. Forst. bark and its extracts, obtained sequentially with n-hexane, acetone, and methanol, against Gaeumannomyces graminis var. tritici (Ggt. Ground bark of D. winteri was mixed with potato dextrose agar growth media at concentrations of 250, 500, 1000, 2000, and 4000 mg L-1 in Petri plates. Each extract was mixed at concentrations of 100, 200, 400, and 800 mg L-1. Petri plates were inoculated in the center with a 5-mm mycelium disk and were incubated at 24 ± 1 ºC. Daily measurements of mycelium radial growth were taken to determine growth rate and growth inhibition (%. A ground bark concentration of 978 mg L-1 was needed to inhibit Ggt growth by 50%, while extracts obtained with n-hexane and acetone only required 198 and 234 mg L-1, respectively. The methanol extract only inhibited Ggt growth by 33% when tested at the highest concentration. In conclusion, ground bark and crude extracts, obtained sequentially with n-hexane, acetone, and methanol, from D. winteri bark inhibit Ggt growth when applied in vitro. The n-hexane extract showed the highest inhibitory growth activity.El objetivo de esta investigación fue evaluar la actividad de la corteza de Drimys winteri J.R Forst. & G. Forst. y sus extractos obtenidos secuencialmente con n-hexano, acetona y metanol sobre el crecimiento in vitro de Gaeumannomyces graminis var. tritici (Ggt. Con este propósito se mezclaron en placas Petri, corteza molida de D. winteri con medio de crecimiento agar papa dextrosa a concentraciones de 250, 500, 1000, 2000 y 4000 mg L-1. Cada extracto fue mezclado a concentraciones de 100, 200, 400 y 800 mg L-1. Las placas se inocularon en su centro con un disco de 5 mm de micelio de Ggt y se incubaron a 24 ± 1 ºC. Diariamente se midió el crecimiento radial del micelio, se determinó velocidad de crecimiento e índice de inhibición del crecimiento (%. Para inhibir el crecimiento de Ggt

  3. Evaluación de la actividad tóxica y antifúngica del extracto etéreo de la corteza de Celtis trinervia Lam (Ulmaceae

    Directory of Open Access Journals (Sweden)

    Torrenegra R. D.

    2000-12-01

    Full Text Available

    A la fracción evaluada biológicarnente se encontró actividad toxica sobre Artemia salina mostrando una CL50 de 430 ppm y antifúngicas contra Fusarium oxysporum ssp dianthi en donde mostro CL50 de 0.25 mg/mL. La fracción evaluada del extracto etéreo de la corteza del rallo de Celtis trinervia Lam. Se identificaron sustancias de tipo terpénicas como santaleno, además se identificaron ácidos grasos saturados e insaturados de interés biológico, como el linoleico y oleico. Los compuestos aislados se identificaron can métodos físicos. químicos y espectroscópicos.

  4. Evaluación mineralógica semi-cuantitativa de las cortezas de meteorización no niquelíferas en la región nororiental de Cuba

    Directory of Open Access Journals (Sweden)

    Gerardo Orozco-Melgar

    2010-03-01

    Full Text Available Este estudio presenta una evaluación mineralógica semi-cuantitativa de las cortezas de meteorización no niquelíferas en las áreas de Baconal, El Culebro, Caimanes y Farallones en la región nororiental de Cuba. El objetivo principal del presente trabajo es determinar las principales fases minerales, su distribución, concentración y grado de transformación de los minerales en los perfiles de meteorización. Las muestras, 16 en total, se analizaron mediante Difracción de Rayos X; los resultados se procesaron con los programas ANALYZE y AUTOQUAN. El grado de transformación de los minerales en relación con la distribución, concentración de las fases y el avance de la meteorización se determinó por el Índice Mineralógico de Alteración. Las principales fases minerales presentes en Baconal y El Culebro son caolinita (50-75%, caolinita- montmorillonita (50-75%,cuarzo (25-50%, plagioclasas, principalmente albita (25-50% y hematita (<10%. En Caimanes y Farallones las fases principales son caolinita hematita, cuarzo, feldespatos potásicos, principalmente ortoclasa, todos en más de un 50-75%. También están presentes la halloysita (<10% y montmorillonita (<10%. Se evidencia una transformación mineral extrema en los horizontes intermedios y superiores en Baconal, El Culebro y Caimanes (Índice Mineralógico de Alteración con valores entre 29 y 98%. Esta transformación también se observa en el perfil completo de Farallones (98-99%. Se concluye que las cortezas de meteorización en Baconal, El Culebro, Caimanes y Farallones son principalmente arcillas caoliníticas.

  5. Medial thalamic 18-FDG uptake following inescapable shock correlates with subsequent learned helpless behavior

    Energy Technology Data Exchange (ETDEWEB)

    Mirrione,M.M.; Mirrione, M.M.; Schulz, D.; Dewey, S.L.; Henn, F.A.

    2009-12-06

    correlations were found in additional regions analyzed including the nucleus accumbens, caudate putamen, substantia nigra, and amygdala. These data suggest that medial thalamic 18-FDG uptake during inescapable shock may contribute to subsequent escape deficits, and are not confounded by shock effects per se, since all animals received the same treatment prior to scanning. We have previously explored 18-FDG differences following the escape test session which also showed hyperactivity in the medial thalamus of learned helpless animals compared to non-learned helpless, and included additional cortical-limbic changes. Given the neuroanatomical connections between the medial thalamus (and habenula) with the prefrontal cortex and monoaminergic brain stem, one possible speculation is that abnormal neuronal activity in these areas during stress may set in motion circuitry changes that correlate with learned helpless behavior.

  6. Medial Cochlear Efferent Function: A Theoretical Analysis

    Science.gov (United States)

    Mountain, David C.

    2011-11-01

    Since the discovery of the cochlear efferent system, many hypotheses have been put forth for its function. These hypotheses for its function range from protecting the cochlea from over stimulation to improving the detection of sounds in noise. It is known that the medial efferent system innervates the outer hair cells and that stimulation of this system reduces basilar membrane and auditory nerve sensitivity which suggests that this system acts to decrease the gain of the cochlear amplifier. Here I present modeling results as well as analysis of published experimental data that suggest that the function of the medial efferent reflex is to decrease the cochlear amplifier gain by just the right amount so that the nonlinearity in the basilar membrane response lines up perfectly with the inner hair cell nonlinear transduction process to produce a hair cell receptor potential that is proportional to the logarithm of the sound pressure level.

  7. [SECOT consensus on medial femorotibial osteoarthritis].

    Science.gov (United States)

    Moreno, A; Silvestre, A; Carpintero, P

    2013-01-01

    A consensus, prepared by SECOT, is presented on the management of medial knee compartment osteoarthritis, in order to establish clinical criteria and recommendations directed at unifying the criteria in its management, dealing with the factors involved in the pathogenesis of medial femorotibial knee osteoarthritis, the usefulness of diagnostic imaging techniques, and the usefulness of arthroscopy. Conservative and surgical treatments are also analysed. The experts consulted showed a consensus (agreed or disagreed) in 65.8% of the items considered, leaving 14items where no consensus was found, which included the aetiopathogenesis of the osteoarthritis, the value of NMR in degenerative disease, the usefulness of COX-2 and the chondroprotective drugs, as well as on the ideal valgus tibial osteotomy technique. © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  8. Masseter and medial pterygoid muscle hypertrophy.

    Science.gov (United States)

    Guruprasad, R; Rishi, Sudhirkumar; Nair, Preeti P; Thomas, Shaji

    2011-09-26

    Hypertrophy refers to an enlargement caused by an increase in the size but not in the number of cells. Generalised masticatory muscle hypertrophy may affect the temporalis muscle, masseters and medial pterygoids in a variety of combinations. Masseteric hypertrophy may present as either unilateral or bilateral painless swelling of unknown origin in the region of angle of mandible. It is a relatively rare condition and presents a diagnostic dilemma. While the history and clinical examination are important in differentiating this benign condition from parotid or dental pathology, they cannot necessarily exclude rare malignant lesion within the muscle. Advanced imaging modalities like CT and MRI are essential to confirm the diagnosis. Here the authors are reporting a unique case of masseter muscle hypertrophy along with medial pterygoid hypertrophy which was missed clinically but confirmed using CT and MRI.

  9. Prefrontal control of the amygdala during real-time fMRI neurofeedback training of emotion regulation

    CERN Document Server

    Zotev, Vadim; Young, Kymberly D; Drevets, Wayne C; Bodurka, Jerzy

    2013-01-01

    We observed in a previous study (PLoS ONE 6:e24522) that the self-regulation of amygdala activity via real-time fMRI neurofeedback (rtfMRI-nf) with positive emotion induction was associated, in healthy participants, with an enhancement in the functional connectivity between the left amygdala (LA) and six regions of the prefrontal cortex. These regions included the left rostral anterior cingulate cortex (rACC), bilateral dorsomedial prefrontal cortex (DMPFC), bilateral superior frontal gyrus (SFG), and right medial frontopolar cortex (MFPC). Together with the LA, these six prefrontal regions thus formed the functional neuroanatomical network engaged during the rtfMRI-nf procedure. Here we perform a structural vector autoregression (SVAR) analysis of the effective connectivity for this network. The SVAR analysis demonstrates that the left rACC plays an important role during the rtfMRI-nf training, modulating the LA and the other network regions. According to the analysis, the rtfMRI-nf training leads to a signi...

  10. Long-Term Effects of Acute Stress on the Prefrontal-Limbic System in the Healthy Adult

    Science.gov (United States)

    Wei, Dongtao; Du, Xue; Zhang, Qinglin; Liu, Guangyuan; Qiu, Jiang

    2017-01-01

    Most people are exposed to at least one traumatic event during the course of their lives, but large numbers of people do not develop posttraumatic stress disorders. Although previous studies have shown that repeated and chronic stress change the brain’s structure and function, few studies have focused on the long-term effects of acute stressful exposure in a nonclinical sample, especially the morphology and functional connectivity changes in brain regions implicated in emotional reactivity and emotion regulation. Forty-one months after the 5/12 Wenchuan earthquake, we investigated the effects of trauma exposure on the structure and functional connectivity of the brains of trauma-exposed healthy individuals compared with healthy controls matched for age, sex, and education. We then used machine-learning algorithms with the brain structural features to distinguish between the two groups at an individual level. In the trauma-exposed healthy individuals, our results showed greater gray matter density in prefrontal-limbic brain systems, including the dorsal anterior cingulate cortex, medial prefrontal cortex, amygdala and hippocampus, than in the controls. Further analysis showed stronger amygdala-hippocampus functional connectivity in the trauma-exposed healthy compared to the controls. Our findings revealed that survival of traumatic experiences, without developing PTSD, was associated with greater gray matter density in the prefrontal-limbic systems related to emotional regulation. PMID:28045980

  11. Reelin-Haploinsufficiency Disrupts the Developmental Trajectory of the E/I Balance in the Prefrontal Cortex.

    Science.gov (United States)

    Bouamrane, Lamine; Scheyer, Andrew F; Lassalle, Olivier; Iafrati, Jillian; Thomazeau, Aurore; Chavis, Pascale

    2016-01-01

    The reelin gene is a strong candidate in the etiology of several psychiatric disorders such as schizophrenia, major depression, bipolar disorders, and autism spectrum disorders. Most of these diseases are accompanied by cognitive and executive-function deficits associated with prefrontal dysfunctions. Mammalian prefrontal cortex (PFC) development is characterized by a protracted postnatal maturation constituting a period of enhanced vulnerability to psychiatric insults. The identification of the molecular components underlying this prolonged postnatal development is necessary to understand the synaptic properties of defective circuits participating in these psychiatric disorders. We have recently shown that reelin plays a key role in the maturation of glutamatergic functions in the postnatal PFC, but no data are available regarding the GABAergic circuits. Here, we undertook a cross-sectional analysis of GABAergic function in deep layer pyramidal neurons of the medial PFC of wild-type and haploinsufficient heterozygous reeler mice. Using electrophysiological approaches, we showed that decreased reelin levels impair the maturation of GABAergic synaptic transmission without affecting the inhibitory nature of GABA. This phenotype consequently impacted the developmental sequence of the synaptic excitation/inhibition (E/I) balance. These data indicate that reelin is necessary for the correct maturation and refinement of GABAergic synaptic circuits in the postnatal PFC and therefore provide a mechanism for altered E/I balance of prefrontal circuits associated with psychiatric disorders.

  12. Perseveration in the presence of punishment: the effects of chronic cocaine exposure and lesions to the prefrontal cortex.

    Science.gov (United States)

    Allen, Craig P; Leri, Francesco

    2014-03-15

    Perseveration is the repetition of a previously appropriate response in a manner, or context, which is detrimental to the individual. Although both cocaine exposure and prefrontal cortex (PFC) dysfunctions have been implicated in perseverative-like behaviours, the underlying nature of the impairments has been debated. The current study tested whether chronic cocaine exposure and PFC lesions induce perseverative-like behaviours by causing insensitivity to punishment. Food-restricted male Sprague-Dawley rats were trained to respond for sucrose on concurrent schedules of reinforcement. After initial training, rats received either a sensitizing regimen of cocaine exposure, or excitotoxic lesions to subregions of the PFC. The test of perseveration involved a choice of responding between two levers associated with fixed ratio and progressive ratio (PR) schedules. Responding on the PR lever was punished by a 1 min timeout period. It was found that, unlike control subjects, those exposed to chronic cocaine, or with lesions to the medial prefrontal cortex, were significantly slower in adapting their responding to avoid punishment. The current study provides evidence that both cocaine exposure and lesions to the prefrontal cortex can increase perseverative-like responding, although the magnitude and permanence of these effects are contingent on the nature of the task.

  13. Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats

    Directory of Open Access Journals (Sweden)

    Victoria Andino-Pavlovsky

    2017-05-01

    Full Text Available Dopamine release and phase-amplitude cross-frequency coupling (CFC have independently been implicated in prefrontal cortex (PFC functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP recorded from the medial PFC (mPFC of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC.

  14. Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

    Directory of Open Access Journals (Sweden)

    Marlos Vasconcelos Rocha

    2015-01-01

    Full Text Available Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD, but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS. The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS. Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS. Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects. Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.

  15. Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder.

    Science.gov (United States)

    Buchsbaum, Monte S; Nenadic, Igor; Hazlett, Erin A; Spiegel-Cohen, Jacqueline; Fleischman, Michael B; Akhavan, Arash; Silverman, Jeremy M; Siever, Larry J

    2002-03-01

    In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients.

  16. Masseter and medial pterygoid muscle hypertrophy

    OpenAIRE

    R, Guruprasad; Rishi, Sudhirkumar; Nair, Preeti P; Thomas, Shaji

    2011-01-01

    Hypertrophy refers to an enlargement caused by an increase in the size but not in the number of cells. Generalised masticatory muscle hypertrophy may affect the temporalis muscle, masseters and medial pterygoids in a variety of combinations. Masseteric hypertrophy may present as either unilateral or bilateral painless swelling of unknown origin in the region of angle of mandible. It is a relatively rare condition and presents a diagnostic dilemma. While the history and clinical examination ar...

  17. Functional bundles of the medial patellofemoral ligament.

    Science.gov (United States)

    Kang, Hui Jun; Wang, Fei; Chen, Bai Cheng; Su, Yan Ling; Zhang, Zhan Chi; Yan, Chang Bao

    2010-11-01

    The purpose of this study was to explore the anatomy and evaluate the function of the medial patellofemoral ligament (MPFL). Anatomical dissection was performed on 12 fresh-frozen knee specimens. The MPFL is a condensation of capsular fibers, which originates at the medial femoral condyle. It runs transversely and inserts to the medial edge of the patella. With the landmark of the medial femur epicondyle (MFE), the femoral origination was located: just 8.90 ± 3.27 mm proximally and 13.47 ± 3.68 mm posteriorly to the MFE. The most interesting finding in present study was functional bundles of its patellar insertion. Approximately from the femoral origination point, fibers of the MPFL form two relatively concentrated fiber bundles: the inferior-straight bundle and the superior-oblique bundle. The whole length of each was 71.78 ± 5.51 and 73.67 ± 5.40 mm, respectively. The included angle between bundles was 15.1° ± 2.1°. Although the superior-oblique bundle and the inferior-straight bundle run on the patellar MPFL inferiorly and superiorly, respectively, as their name indicates, the two bundles are not entirely separated, which make MPFL one intact structure. The inferior-straight bundle is the main static soft tissue restraints where the superior-oblique bundle associated with vastus medialis obliquus (VMO) is to serve as the main dynamic soft tissue restraints. So this finding may provide the theoretical foundation for the anatomical reconstruction of the MPFL and shed lights on the future researchers.

  18. Social appraisal in chronic psychosis: Role of medial frontal and occipital networks

    Science.gov (United States)

    Taylor, Stephan F.; Chen, Ashley C.; Tso, Ivy F.; Liberzon, Israel; Welsh, Robert C.

    2010-01-01

    Persons with schizophrenia often appraise other individuals as threatening or persecutory. To evaluate social appraisal in schizophrenia, we probed brain networks with a task in which subjects judged whether or not they liked face stimuli with emotional expressions. We predicted that appraising negative expressions would engage patients, more than controls, and negative faces would be related to higher levels of negative affect and produce increased activity in the medial frontal cortex, an area involved in social appraisal. Twenty-one stable outpatients with chronic non-affective psychosis (16 schizophrenic, 5 schizoaffective) and 21 healthy subjects underwent functional magnetic resonance imaging. Compared with the control subjects, patients were slower to respond, but particularly slow when they judged negatively-valenced faces, a slowness correlated with negative affect in the psychosis patients. Appraisal activated the medial prefrontal cortex (mPFC) across all face valences. For negative expressions, patients exhibited greater activation of the dorsal anterior cingulate cortex (dACC). A psychophysiological interaction analysis of the dACC revealed co-modulation of the mPFC in controls, significantly less in patients, and a trend for co-modulation of occipital cortex in the patients. Activity in occipital cortex correlated with poor social adjustment and impaired social cognition, and co-modulation of the occipital gyrus by the dACC was correlated with poorer social cognition. The findings link appraisal of negative affect with aberrant activation of the medial frontal cortex, while early sensory processing of this social cognitive task was linked with poor social function, reflecting either top down or bottom up influences. PMID:20797730

  19. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

    Science.gov (United States)

    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Post-ablative reconstruction of the medial canthus and medial orbital wall using conchal cartilage graft with three illustrative cases.

    Science.gov (United States)

    Dagregorio, G; Darsonval, V

    2005-12-01

    When the medial third of the upper or lower eyelid has to be reconstructed after full-thickness tumour excision, we usually use Hübner tarsomarginal grafts, but when medial canthal lesions spread to the medial orbital wall without invading the orbital margin, conchal graft becomes our first surgical option. Previously reported solutions to this difficult problem are few and concern more directly medial orbital wall fractures. We found no article dealing specifically with the use of conchal graft in post-ablative reconstruction of the medial orbital wall. Nevertheless the concha presents great advantages over bone grafting or rib cartilage, because it is more flexible and malleable. And it is less prone to extrusion or infection as may be allografts implants. It is a very effective way to repair medial orbital defects, but graft reorientation must be perfect to match exactly the medial orbital wall concavity.

  1. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Klumpers, F.; Fernandez, G.S.E.

    2016-01-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to diff

  2. Medial Prefrontal Cortex and HPA Axis Roles in Generation of PTSD-Like Symptoms in SPS Model

    Science.gov (United States)

    2012-09-01

    warmedwith a water- irculating heat pad (Gaymar Industries, Orchard Park, NY). Stereotaxic surgery was performed by securing rats in a Kopf tereotaxic...Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001; 14(4):260–264. [PubMed: 11410943] 40. Nicholls, D

  3. Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex

    DEFF Research Database (Denmark)

    Littlefield, Melissa M; Dietz, Martin; Fitzgerald, Des

    2015-01-01

    of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in...

  4. Gene expression changes in the medial prefrontal cortex and nucleus accumbens following abstinence from cocaine self-administration

    Directory of Open Access Journals (Sweden)

    Morgan Drake

    2010-02-01

    Full Text Available Abstract Background Many studies of cocaine-responsive gene expression have focused on changes occurring during cocaine exposure, but few studies have examined the persistence of these changes with cocaine abstinence. Persistent changes in gene expression, as well as alterations induced during abstinence may underlie long-lasting drug craving and relapse liability. Results Whole-genome expression analysis was conducted on a rat cocaine binge-abstinence model that has previously been demonstrated to engender increased drug seeking and taking with abstinence. Gene expression changes in two mesolimbic terminal fields (mPFC and NAc were identified in a comparison of cocaine-naïve rats with rats after 10 days of cocaine self-administration followed by 1, 10, or 100 days of enforced abstinence (n = 6-11 per group. A total of 1,461 genes in the mPFC and 414 genes in the NAc were altered between at least two time points (ANOVA, p Conclusions Together, these changes help to illuminate processes and networks involved in abstinence-induced behaviors, including synaptic plasticity, MAPK signaling, and TNF signaling.

  5. Stress-induced impairment of glutamatergic terminals ultrastructure: High vulnerability of medial prefrontal cortex and preventing action of desipramine

    DEFF Research Database (Denmark)

    Nava, N.; Popoli, M.; Musazzi, L.

    2013-01-01

    volume quantified [2]. Distribution of glutamatergic synaptic terminals was evaluated with immunohistochemistry. Asymmetric-glutamatergic synapses were identified and the size of readilyreleasable pool and reserve-pool of vesicles estimated, through serial section electron microscopy. Extension of post...

  6. Stress-induced impairment of glutamatergic terminals ultrastructure: High vulnerability of medial prefrontal cortex and preventing action of desipramine

    DEFF Research Database (Denmark)

    Nava, N.; Popoli, M.; Musazzi, L.

    2013-01-01

    mediators, glucocorticoids, on brain volume and dendritic remodeling, in both humans and rodents. Nevertheless, few is still known on the structural changes exerted by behavioral stress on the features of glutamatergic synapses as sites of neuronal communication. Indeed, in excitatory synapses synaptic...... communication is driven by neurotransmitter which is stored, within the presynaptic terminal, in morphologically distinct pools of vesicles, namely the readily-releasable pool of vesicles (RRP), docked to the active zone and ready for release, and the reserve pool of vesicles. When neurotransmitter is released...

  7. Extinction and retrieval+extinction of conditioned fear differentially activate medial prefrontal cortex and amygdala in rats

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    Hongjoo Joanne Lee

    2016-01-01

    Full Text Available Pairing a previously neutral conditioned stimulus (CS; e.g., a tone to an aversive unconditioned stimulus (US; e.g., a footshock leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing. We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval+extinction attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009. To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval+extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these 2 approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization. Our results demonstrate that extinction and retrieval+extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rats.

  8. Observational Learning in Mice Can Be Prevented by Medial Prefrontal Cortex Stimulation and Enhanced by Nucleus Accumbens Stimulation

    Science.gov (United States)

    Jurado-Parras, M. Teresa; Gruart, Agnes; Delgado-Garcia, Jose M.

    2012-01-01

    The neural structures involved in ongoing appetitive and/or observational learning behaviors remain largely unknown. Operant conditioning and observational learning were evoked and recorded in a modified Skinner box provided with an on-line video recording system. Mice improved their acquisition of a simple operant conditioning task by…

  9. Abnormal Functional Specialization within Medial Prefrontal Cortex in High-Functioning Autism: A Multi-Voxel Similarity Analysis

    Science.gov (United States)

    Gilbert, Sam J.; Meuwese, Julia D. I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in "decoding" mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males)…

  10. LANGUAGE-DRIVEN SPATIOTEMPORAL CAUSAL INTEGRATION IN THE PREFRONTAL AND PREMOTOR CORTICES MODULACIÓN LINGÜÍSTICA DE LA INTEGRACIÓN ESPACIO-TEMPORAL DE LA INFORMACIÓN CAUSAL EN LAS ÁREAS PREFRONTAL Y PREMOTORA DE LA CORTEZA CEREBRAL

    Directory of Open Access Journals (Sweden)

    ROBERTO LIMONGI TIRADO¹

    2011-01-01

    Full Text Available The behavioral literature has reported the differentiation between perceived causality and higher-order causal reasoning. The advent of modern technology such as functional magnetic resonance imaging and the theoretical framework of cognitive linguistics and behavioral experimental designs have raised new hypotheses and opened new possibilities to address the perceptual and higher-order distinction in causality. In this article, we discuss and integrate recent biological and psycholinguistic work on both perceptual and linguistic representations of causality that challenges the modular view of human causal knowledge. We suggest that linguistic and sensory-perceptual representations of causal events might coexist and interact in the brain. In this sense, whereas previous work proposes that the posterior areas of the brain automatically detect the spatiotemporal structure of visual causal events and that the frontal areas integrate such information in a causal representation, results from our research program suggest that this integration process is language-driven. Tw o different semantic representations of causative linguistic structures (lexical and periphrastic causatives might infuence cognitive control mechanisms, memory resources, and preparatory motor responses when observers evaluate the causal nature of visual stimuli.La bibliografía conductual ha reportado diferencias entre los procesos de percepción causal y procesos superiores de razonamiento causal. El desarrollo de nuevas tecnologías como la resonancia magnética nuclear funcional, la perspectiva teórica de la lingüística cognitiva y los diseños experimentales conductuales han propiciado nuevas hipótesis y abierto nuevas posibilidades para abordar la diferencia entre percepción causal y razonamiento causal. En este artículo discutimos e integramos los recientes avances biológicos y psicolingüísticos sobre las representaciones perceptuales y lingüísticas de la causalidad que desafían la visión modular del conocimiento causal en el humano. Sugerimos que las representaciones lingüísticas y sensorio-perceptuales de eventos causales podrían coexistir e interactuar en el cerebro. En este sentido, mientras trabajos anteriores proponen que las áreas posteriores del cerebro detectan automáticamente la estructura espacio-temporal de los eventos causales visuales y que áreas frontales integran esa información en una representación causal, los resultados de nuestro programa de investigación sugieren que este proceso es modulado por el lenguaje. Las representaciones semánticas de dos estructuras lingüísticas diferentes (léxica y perifrástica podrían influir en los mecanismos de control cognoscitivo, los recursos de memoria y las respuestas motoras preparatorias cuando los participantes evalúan la naturaleza causal de los eventos visuales.

  11. Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

    Directory of Open Access Journals (Sweden)

    Glen eAcosta

    2012-01-01

    Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

  12. Chrna5 genotype determines the long-lasting effects of developmental in vivo nicotine exposure on prefrontal attention circuitry

    Science.gov (United States)

    Bailey, Craig D.C.; Tian, Michael K.; Kang, Lily; O’Reilly, Ryan; Lambe, Evelyn K.

    2015-01-01

    Maternal smoking during pregnancy repeatedly exposes the developing fetus to nicotine and is linked with attention deficits in offspring. Corticothalamic neurons within layer VI of the medial prefrontal cortex are potential targets in the disruption of attention circuitry by nicotine, a process termed teratogenesis. These prefrontal layer VI neurons would be likely targets because they are developmentally excited and morphologically sculpted by a population of nicotinic acetylcholine receptors (nAChRs) that are sensitive to activation and/or desensitization by nicotine. The maturational effects of these α4β2* nAChRs and their susceptibility to desensitization are both profoundly altered by the incorporation of an α5 subunit, encoded by the chrna5 gene. Here, we investigate nicotine teratogenesis in layer VI neurons of wildtype and α5−/− mice. In vivo chronic nicotine exposure during development significantly modified apical dendrite morphology and nAChR currents, compared with vehicle control. The direction of the changes was dependent on chrna5 genotype. Surprisingly, neurons from wildtype mice treated with in vivo nicotine resembled those from α5−/− mice treated with vehicle, maintaining into adulthood a morphological phenotype characteristic of immature mice together with reduced nAChR currents. In α5−/− mice, however, developmental in vivo nicotine tended to normalize both adult morphology and nAChR currents. These findings suggest that chrna5 genotype can determine the effect of developmental in vivo nicotine on the prefrontal cortex. In wildtype mice, the lasting alterations to the morphology and nAChR activation of prefrontal layer VI neurons are teratogenic changes consistent with the attention deficits observed following developmental nicotine exposure. PMID:24055499

  13. Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor.

    Science.gov (United States)

    Kern, Simone; Oakes, Terrence R; Stone, Charles K; McAuliff, Emelia M; Kirschbaum, Clemens; Davidson, Richard J

    2008-05-01

    The prefrontal cortex (PFC) has been well known for its role in higher order cognition, affect regulation and social reasoning. Although the precise underpinnings have not been sufficiently described, increasing evidence also supports a prefrontal involvement in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation during a psychosocial stress exposure in 14 healthy humans. Regional brain metabolism was assessed using positron emission tomography (PET) and injection of fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC, increased glucose metabolic rate was associated with lower or higher salivary cortisol concentration in response to a psychosocial stress condition. Metabolic glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was negatively associated with stress-induced salivary cortisol increases. Furthermore, metabolic glucose rate in these regions was inversely coupled with changes in glucose metabolic rate in other areas, known to be involved in HPA axis regulation such as the amygdala/hippocampal region. In contrast, metabolic glucose rate in areas more lateral to the mPFC was positively associated with saliva cortisol. Subjective ratings on task stressfulness, task controllability and self-reported dispositional mood states also showed positive and negative associations with the glucose metabolic rate in prefrontal regions. These findings suggest that in humans, the PFC is activated in response to psychosocial stress and distinct prefrontal metabolic glucose patterns are linked to endocrine stress measures as well as subjective ratings on task stressfulness, controllability as well as dispositional mood states.

  14. Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Pettit, Lewis D; Bastin, Mark E; Smith, Colin; Bak, Thomas H; Gillingwater, Thomas H; Abrahams, Sharon

    2013-11-01

    , uncinate fasciculus and hippocampal portion of the cingulum bundles. Significant differences also emerged in the anterior corona radiata as well as in white matter underlying the superior, medial and inferior frontal gyri and the temporal gyri. Dual-task performance significantly correlated with fractional anisotropy measures in the middle frontal gyrus white matter and anterior corona radiata. Letter fluency indices significantly correlated with fractional anisotropy measures of the inferior frontal gyrus white matter and corpus callosum in addition to the corticospinal tracts and mean diffusivity measures in the white matter of the superior frontal gyrus. The current study demonstrates that cognitive impairment in amyotrophic lateral sclerosis is not due to generic slowing of processing speed. Moreover, different executive deficits are related to distinct prefrontal tract involvement in amyotrophic lateral sclerosis with dual-task impairment associating with dorsolateral prefrontal dysfunction and letter fluency showing greater dependence on inferolateral prefrontal dysfunction.

  15. Lack of serotonin reuptake during brain development alters rostral raphe-prefrontal network formation

    Directory of Open Access Journals (Sweden)

    Josefine Storm Witteveen

    2013-10-01

    Full Text Available Besides its ‘classical’ neurotransmitter function, serotonin (5-HT has been found to also act as a neurodevelopmental signal. During development, the 5-HT projection system represents one of the earliest neurotransmitter systems to innervate the brain. One of the targets of the 5-HT projection system, originating in the brainstem raphe nuclei, is the medial prefrontal cortex (mPFC, an area involved in higher cognitive functions and important in the etiology of many neurodevelopmental disorders. Little is known however about the exact role of 5-HT and its signaling molecules in the formation of the raphe-prefrontal network. Using explant essays, we here studied the role of the 5-HT transporter (5-HTT, an important modulator of the 5-HT signal, in rostral raphe-prefrontal network formation. We found that the chemotrophic nature of the interaction between the origin (rostral raphe cluster and a target (mPFC of the 5-HT projection system was affected in rats lacking the 5-HTT (5-HTT-/-. While 5-HTT deficiency did not affect the dorsal raphe 5-HT-positive outgrowing neurites, the median raphe 5-HT neurites switched from a strong repulsive to an attractive interaction when co-cultured with the mPFC. Furthermore, the fasciculation of the mPFC outgrowing neurites was dependent on the amount of 5-HTT. In the mPFC of 5-HTT-/- pups, we observed clear differences in 5-HT innervation and the identity of a class of projection neurons of the mPFC. In the absence of the 5-HTT, the 5-HT innervation in all subareas of the early postnatal mPFC increased dramatically and the number of Satb2-positive callosal projection neurons was decreased. Together, these results suggest a 5-HTT dependency during early development of these brain areas and in the formation of the raphe-prefrontal network. The tremendous complexity of the 5-HT projection system and its role in several neurodevelopmental disorders highlights the need for further research in this largely

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

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.AllAg.Prefrontal_Cortex hg19 RNA polymerase Neural Prefrontal Cortex htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.20.AllAg.Prefrontal_Cortex.bed ...

  17. File list: Pol.Neu.50.AllAg.Prefrontal_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.AllAg.Prefrontal_Cortex hg19 RNA polymerase Neural Prefrontal Cortex htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.50.AllAg.Prefrontal_Cortex.bed ...

  18. File list: Pol.Neu.05.AllAg.Prefrontal_Cortex [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.AllAg.Prefrontal_Cortex hg19 RNA polymerase Neural Prefrontal Cortex htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.05.AllAg.Prefrontal_Cortex.bed ...

  19. a7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the a7 nicotinic acetylcholine receptor (n......AChR) agonist SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be normalized once they have already occurred. Here we use semi-quantitative in situ hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d. for 5 days) subsequent to repeated PCP administration...... (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  20. α7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the α7 nicotinic acetylcholine receptor (n......AChR) agonist SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be normalized once they have already occurred. Here we use semi-quantitative in situ hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d. for 5 days) subsequent to repeated PCP administration...... (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  1. Microsurgical treatment of medial sphenoid ridge meningioma

    Directory of Open Access Journals (Sweden)

    Wei-qi HE

    2011-02-01

    Full Text Available Objective To explore the microsurgical technique of medial sphenoid ridge meningioma resectional therapy.Methods The clinical data were retrospectively analyzed of 29 patients(13 males and 16 females;aged 18-68 years with average of 42 years;duration of disease was 5 months to 8 years,averaged 28 months with medial sphenoidal ridge meningioma and admitted from Jan.2005 to Jan.2010.The anatomical relationship of the tumor to surrounding structures was assessed intraoperatively,the tumor was then completely resected through cutting off the tumor supplying vessels,shrinking the tumor volume and separating the tumors from adjacent vessels and nerves.All the patients were followed up for 4 months to 4 years.Results Of the 29 cases,20 got total tumor removal,7 got subtotal and 2 got partial tumor removal.Of the 20 patients with obviously preoperative visual impairment,12 were obviously relieved,6 showed no improvement and 2 got symptoms aggravation.Hemiplegia occurred in 2 cases and oculomoter nerve palsy in 6 cases.There was no death after surgery.A 6 months to 4 years follow-up showed that no recurrence was found in 27 patients with tumor resection level of Simpson I and II,2 patients with tumor resection level of Simpson III received postoperative radiotherapy or gamma knife surgery,and 1 recurred and received reoperation.Conclusions Fine intraoperative assessment of the anatomical relationship of the tumor to surrounding structures,separating and excising tumor according to the assessed result is the key of medial sphenoid ridge meningioma resection,and the tumor resection is favorable to visual rehabilitation and tumor control.

  2. Prefrontal Cortex: A Mystery of Belated Memories.

    Science.gov (United States)

    Eichenbaum, Howard

    2017-06-05

    A recent study suggests that the prefrontal cortex gradually becomes critical as a storage site for remotely acquired memories. How do we interpret this observation in light of the well-known functional role of the prefrontal cortex in cognition and memory? Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Discourse Production Following Injury to the Dorsolateral Prefrontal Cortex

    Science.gov (United States)

    Coelho, Carl; Le, Karen; Mozeiko, Jennifer; Krueger, Frank; Grafman, Jordan

    2012-01-01

    Individuals with damage to the prefrontal cortex, and the dorsolateral prefrontal cortex (DLPFC) in particular, often demonstrate difficulties with the formulation of complex language not attributable to aphasia. The present study employed a discourse analysis procedure to characterize the language of individuals with left (L) or right (R) DLPFC…

  4. Magnetoencephalographic signatures of right prefrontal cortex involvement in response inhibition.

    Science.gov (United States)

    Hege, Maike A; Preissl, Hubert; Stingl, Krunoslav T

    2014-10-01

    The prefrontal cortex has a pivotal role in top-down control of cognitive and sensory functions. In complex go-nogo tasks, the right dorsolateral prefrontal cortex is considered to be important for guiding the response inhibition. However, little is known about the temporal dynamics and neurophysiological nature of this activity. To address this issue, we recorded magnetoencephalographic brain activity in 20 women during a visual go-nogo task. The right dorsolateral prefrontal cortex showed an increase for the amplitude of the event-related fields and an increase in induced alpha frequency band activity for nogo in comparison to go trials. The peak of this prefrontal activity preceded the mean reaction time of around 360 ms for go trials, and thus supports the proposed role of right dorsolateral prefrontal cortex in gating the response inhibition and further suggests that right prefrontal alpha band activity might be involved in this gating. However, the results in right dorsolateral prefrontal cortex were similar for both successful and unsuccessful response inhibition. In these conditions, we instead observed pre- and poststimulus differences in alpha band activity in occipital and central areas. Thus, successful response inhibition seemed to additionally depend on prestimulus anticipatory alpha desynchronization in sensory areas as it was reduced prior to unsuccessful response inhibition. In conclusion, we suggest a role for functional inhibition by alpha synchronization not only in sensory, but also in prefrontal areas.

  5. rTMS of the left dorsolateral prefrontal cortex modulates dopamine release in the ipsilateral anterior cingulate cortex and orbitofrontal cortex.

    Directory of Open Access Journals (Sweden)

    Sang Soo Cho

    Full Text Available BACKGROUND: Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson's disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC (areas 9/46 stimulation on prefrontal dopamine (DA. METHODOLOGY/PRINCIPAL FINDINGS: Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [(11C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [(11C]FLB 457 binding potential (BP in the ipsilateral subgenual anterior cingulate cortex (ACC (BA 25/12, pregenual ACC (BA 32 and medial orbitofrontal cortex (BA 11. There were no significant changes in [(11C]FLB 457 BP following right DLPFC rTMS. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [(11C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help to identify the neurobiological effects of TMS for the treatment of different neurological and psychiatric diseases.

  6. Lucid dreaming and ventromedial versus dorsolateral prefrontal task performance.

    Science.gov (United States)

    Neider, Michelle; Pace-Schott, Edward F; Forselius, Erica; Pittman, Brian; Morgan, Peter T

    2011-06-01

    Activity in the prefrontal cortex may distinguish the meta-awareness experienced during lucid dreams from its absence in normal dreams. To examine a possible relationship between dream lucidity and prefrontal task performance, we carried out a prospective study in 28 high school students. Participants performed the Wisconsin Card Sort and Iowa Gambling tasks, then for 1 week kept dream journals and reported sleep quality and lucidity-related dream characteristics. Participants who exhibited a greater degree of lucidity performed significantly better on the task that engages the ventromedial prefrontal cortex (the Iowa Gambling Task), but degree of lucidity achieved did not distinguish performance on the task that engages the dorsolateral prefrontal cortex (the Wisconsin Card Sort Task), nor did it distinguish self-reported sleep quality or baseline characteristics. The association between performance on the Iowa Gambling Task and lucidity suggests a connection between lucid dreaming and ventromedial prefrontal function. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

    Science.gov (United States)

    Wolf, Richard C; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

    2014-06-01

    The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion.