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Thomas F Giustino, Paul J Fitzgerald, Stephen Maren
The medial prefrontal cortex (mPFC) plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL) and infralimbic (IL) subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear...
2016: PloS One
Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist, MGS0039 shows antidepressant effects. However, there are no reports comparing these two compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice, after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluA1) and postsynaptic density protein 95 (PSD-95), and dendritic spine density in selected brain regions were measured...
October 7, 2016: International Journal of Neuropsychopharmacology
Kathryn D Baker, Amy C Reichelt
Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet...
October 5, 2016: Neurobiology of Learning and Memory
Antonio Ferragud, Adam D Howell, Catherine F Moore, Tina L Ta, Marius C Hoener, Valentina Sabino, Pietro Cottone
Compulsive, binge eating of highly palatable food constitutes a core feature of some forms of obesity and eating disorders, as well as of the recently proposed disorder of food addiction. Trace Amine-Associated Receptor 1 (TAAR1) is a highly conserved G-protein-coupled receptor bound by endogenous trace amines. TAAR1 agonists have been shown to reduce multiple behavioral effects of drugs of abuse through their actions on the mesocorticolimbic system. In this study, we hypothesized that TAAR1 may play a role in compulsive, binge-like eating; we tested this hypothesis by assessing the effects of a TAAR1 agonist, RO5256390, in multiple excessive feeding-related behaviors induced by limiting access to a highly palatable diet in rats...
October 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jesus Martin-Cortecero, Angel Nuñez
The medial prefrontal cortex (mPFC) plays a key role in higher functions such as memory and attention. In order to demonstrate sensory responses in the mPFC, we used electrophysiological recordings of urethane-anesthetized rats to record somatosensory-evoked potentials (SEPs) or auditory-evoked potentials (AEPs) elicited by whisker deflections and click stimulation, respectively. Contralateral whisker stimulation or auditory stimuli were also applied to study sensory interference in the mPFC. Interference with other sensory stimuli or recent stimulation history reduced whisker responses in the infralimbic and prelimbic cortices of the ventral mPFC...
October 1, 2016: Neuroscience
Martijn M Selten, Francisca Meyer, Wei Ba, Astrid Vallès, Dorien A Maas, Moritz Negwer, Vivian D Eijsink, Ruben W M van Vugt, Josephus A van Hulten, Nick H M van Bakel, Joey Roosen, Robert J van der Linden, Dirk Schubert, Michel M M Verheij, Nael Nadif Kasri, Gerard J M Martens
Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats...
September 30, 2016: Scientific Reports
Maurizio S Riga, Vicent Teruel-Martí, Connie Sánchez, Pau Celada, Francesc Artigas
Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food...
September 23, 2016: Neuropharmacology
Kai-Wen Geng, Ting He, Rui-Rui Wang, Chun-Li Li, Wen-Jun Luo, Fang-Fang Wu, Yan Wang, Zhen Li, Yun-Fei Lu, Su-Min Guan, Jun Chen
Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats...
October 2016: Neuroscience Bulletin
Cristina Mediavilla, Mar Martin-Signes, Severiano Risco
Flavour aversion learning (FAL) and conditioned flavour preference (CFP) facilitate animal survival and play a major role in food selection, but the neurobiological mechanisms involved are not completely understood. Neuroanatomical bases of CFP were examined by using Fos immunohistochemistry to record neuronal activity. Rats were trained over eight alternating one-bottle sessions to acquire a CFP induced by pairing a flavour with saccharin (grape was CS+ in Group 1; cherry in Group 2; in Group 3, grape/cherry in half of animals; Group 4, grape/cherry in water)...
2016: Scientific Reports
Chengji Piao, Xiaofei Deng, Xingyue Wang, Yiran Yuan, Zhengkui Liu, Jing Liang
The medial prefrontal cortex (mPFC) and its output area, the nucleus accumbens (NAc), are implicated in mediating attentional set-shifting. Patients with posttraumatic stress disorder (PTSD) exhibit difficulties in the disengagement of attention from traumatic cues, which is associated with impairments in set-shifting ability. However, unknown is whether alterations in corticostriatal function underlie deficits in this behavioral flexibility in individuals with PTSD. An animal model of single prolonged stress (SPS) has been partially validated as a model for PTSD, in which SPS rats recapitulate the pathophysiological abnormalities and behavioral characteristics of PTSD...
September 8, 2016: Behavioural Brain Research
Manoel Jorge Nobre
Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use...
September 9, 2016: International Journal of Developmental Neuroscience
Laura M McGarry, Adam G Carter
UNLABELLED: Interactions between the prefrontal cortex (PFC) and basolateral amygdala (BLA) regulate emotional behaviors. However, a circuit-level understanding of functional connections between these brain regions remains incomplete. The BLA sends prominent glutamatergic projections to the PFC, but the overall influence of these inputs is predominantly inhibitory. Here we combine targeted recordings and optogenetics to examine the synaptic underpinnings of this inhibition in the mouse infralimbic PFC...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Julie A D Dela Cruz, Tricia Coke, Richard J Bodnar
This study uses cellular c-fos activation to assess effects of novel ingestion of fat and sugar on brain dopamine (DA) pathways in rats. Intakes of sugars and fats are mediated by their innate attractions as well as learned preferences. Brain dopamine, especially meso-limbic and meso-cortical projections from the ventral tegmental area (VTA), has been implicated in both of these unlearned and learned responses. The concept of distributed brain networks, wherein several sites and transmitter/peptide systems interact, has been proposed to mediate palatable food intake, but there is limited evidence empirically demonstrating such actions...
August 24, 2016: Journal of Visualized Experiments: JoVE
Caitlin V Cosme, Andrea L Gutman, Wensday R Worth, Ryan T LaLumiere
Evidence suggests that the infralimbic cortex (IL), a subregion of the ventromedial prefrontal cortex (vmPFC), suppresses cocaine-seeking behavior in a self-administration paradigm, whereas the more anterior vmPFC subregion, the medial orbitofrontal cortex (mOFC), has received very little attention in this regard. Despite the established dopaminergic innervation of the vmPFC, whether dopamine receptor blockade in each subregion alters the reinstatement of cocaine seeking is unclear. To address this issue, male Sprague-Dawley rats underwent 2 weeks of cocaine self-administration, followed by extinction training and reinstatement testing...
August 31, 2016: Addiction Biology
Joshua D Croteau, Jay Schulkin, Jack D Shepard
The medial prefrontal cortex is a key mediator of behavioral aspects of the defense response. Since chronic exposure to elevated glucocorticoids alters the dendritic structure of neurons in the medial prefrontal cortex, such exposure may alter behavioral responses to danger as well. We examined the effects of chronically elevated corticosterone in discrete regions of the medial prefrontal cortex on exploration of the elevated plus-maze. Chronically elevated corticosterone in the prelimbic or infralimbic cortices reduced open arm exploration...
January 1, 2017: Behavioural Brain Research
Eric C Zimmerman, Anthony A Grace
UNLABELLED: The circuitry mediating top-down control of dopamine (DA) neurons in the ventral tegmental area (VTA) is exceedingly complex. Characterizing these networks will be critical to our understanding of fundamental behaviors, such as motivation and reward processing, as well as several disease states. Previous work suggests that the medial prefrontal cortex (mPFC) exerts a profound influence on VTA DA neuron firing. Recently, our group reported that inhibition of the infralimbic subdivision of the medial prefrontal cortex (ilPFC) increases the proportion of VTA DA neurons that are spontaneously active (i...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Dolores B Vazquez-Sanroman, Reyna D Monje, Michael T Bardo
Nicotine, a major psychoactive component of tobacco smoke, alters gamma-aminobutyric acid (GABA) modulation of dopamine neurons in the ventral tegmental area (VTA). Changes in structural neuroplasticity can occur in GABAergic parvalbumin (PRV) positive neurons, which are enveloped by structures of the extracellular matrix called perineuronal nets (PNNs). In the current study, rats were trained to self-administer intravenous nicotine (0.03 mg/kg/infusion) for 21 days in 1-hour daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions...
August 22, 2016: Addiction Biology
Andrea L Gutman, Victoria A Ewald, Caitlin V Cosme, Wensday R Worth, Ryan T LaLumiere
The infralimbic and prelimbic (IL and PL, respectively) regions of the medial prefrontal cortex regulate the control of drug-seeking behavior. However, their roles in cocaine seeking in a discriminative stimulus (DS)-based self-administration task are unclear. To address this issue, male Sprague Dawley rats were trained on a DS task in which, on a trial-by-trial basis, a DS+ indicated that a lever press would produce a cocaine infusion, whereas a distinct DS- indicated that a lever press would produce nothing...
August 22, 2016: Addiction Biology
Ellen M McGlinchey, Morgan H James, Stephen V Mahler, Caroline Pantazis, Gary Aston-Jones
UNLABELLED: Glutamate inputs to nucleus accumbens (NAc) facilitate conditioned drug-seeking behavior and primarily originate from medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral subiculum of the hippocampus (vSub). These regions express Fos (a marker of neural activity) during cue-induced reinstatement of cocaine seeking, but only subpopulations of neurons within these regions drive drug seeking. One way to identify and functionally distinguish neural subpopulations activated during drug-seeking is to examine their projection targets...
August 17, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Davide D'Amico, Thomas Gener, Maria Martínez de Lagrán, Maria V Sanchez-Vives, Mónica Santos, Mara Dierssen
The inability to properly extinguish fear memories constitutes the foundation of several anxiety disorders, including panic disorder. Recent findings show that boosting prefrontal cortex synaptic plasticity potentiate fear extinction, suggesting that therapies that augment synaptic plasticity could prove useful in rescue fear extinction impairments in this group of disorders. Previously, we reported that mice with selective deregulation of neurotrophic tyrosine kinase receptor, type 3 expression (TgNTRK3) exhibit increased fear memories accompanied by impaired extinction, congruent with an altered activation pattern of the amygdala-hippocampus-medial prefrontal cortex fear circuit...
August 18, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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