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E J Marijke Achterberg, Ruth Damsteegt, Louk J M J Vanderschuren
Social play behaviour is a vigorous, highly rewarding social activity abundant in the young of most mammalian species, including humans. Social play is thought to be important for social, emotional and cognitive development, yet its neural underpinnings are incompletely understood. We have previously shown that low doses of methylphenidate suppress social play behaviour through a noradrenergic mechanism of action, and that methylphenidate exerts its effect within the prefrontal cortex, amygdala and habenula...
March 8, 2018: Behavioural Brain Research
Nura W Lingawi, Nathan M Holmes, R Fredrick Westbrook, Vincent Laurent
Evidence indicates that the infralimbic cortex (IL) encodes and retrieves the inhibitory memory produced by fear extinction. Recently, we have shown that the IL is also involved in the inhibitory memory generated by stimulus pre-exposure that causes latent inhibition. These results are surprising because a stimulus undergoing fear extinction carries aversive motivational value, whereas a pre-exposed stimulus is neutral. The present experiments tested the hypothesis that the IL encodes inhibition irrespective of the motivational information about the stimulus...
March 5, 2018: Neurobiology of Learning and Memory
Daniel W Bloodgood, Jonathan A Sugam, Andrew Holmes, Thomas L Kash
Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role...
March 6, 2018: Translational Psychiatry
Sthitapranjya Pati, Ankit Sood, Sourish Mukhopadhyay, Vidita A Vaidya
The medial prefrontal cortex (mPFC) is implicated in anxiety-like behaviour. In rodent models, perturbations of mPFC neuronal activity through pharmacological manipulations, optogenetic activation of mPFC neurons or cell-type specific pharmacogenetic inhibition of somatostatin interneurons indicate conflicting effects on anxiety-like behaviour. In the present study we examined the effects of pharmacogenetic activation of Ca 2+/calmodulin-dependent protein kinase alpha (CamKII alpha)-positive excitatory neurons on anxiety-like behaviour...
March 2018: Journal of Biosciences
Simone Pfarr, Laura Schaaf, Janine K Reinert, Elisabeth Paul, Frank Herrmannsdörfer, Martin Roßmanith, Thomas Kuner, Anita C Hansson, Rainer Spanagel, Christoph Körber, Wolfgang H Sommer
Cue-reward associations form distinct memories that can drive appetitive behaviors and are involved in craving for both drugs and natural rewards. Distinct sets of neurons, so called neuronal ensembles, in the infralimbic area (IL) of the medial prefrontal cortex play a key role in alcohol seeking. Whether this ensemble is specific for alcohol or controls reward seeking in general remains unclear. Here, we compared IL ensembles formed upon recall of drug (alcohol) or natural reward (saccharin) memories in male Wistar rats...
February 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Douglas W Barrett, F Gonzalez-Lima
This study is a new analysis to obtain novel metabolic data on the functional connectivity of prefrontal-limbic regions in Pavlovian fear acquisition and extinction of tone-footshock conditioning. Mice were analyzed with the fluorodeoxyglucose (FDG) autoradiographic method to metabolically map regional brain activity. New FDG data were sampled from the nuclei of the habenula and other regions implicated in aversive conditioning, such as infralimbic cortex, amygdala and periaqueductal gray regions. The activity patterns among these regions were inter-correlated during acquisition, extinction or pseudorandom training to develop a functional connectivity model...
February 22, 2018: Neuroscience
Aina Luque-García, Vicent Teruel-Martí, Sergio Martínez-Bellver, Albert Adell, Ana Cervera-Ferri, Joana Martínez-Ricós
The stress system coordinates the adaptive reactions of the organism to stressors. So, dysfunctions in this circuit may correlate to anxiety-related disorders, including depression. Comprehending the dynamics of this network may lead to a better understanding of the mechanisms that underlie these diseases. The central nucleus of the amygdala (CeA) activates the hypothalamic-pituitary-adrenal axis and brainstem nodes by triggering endocrine, autonomic and behavioural stress responses. The medial prefrontal cortex plays a significant role in regulating reactions to stressors, and is specifically important for limiting fear responses...
February 23, 2018: Journal of Comparative Neurology
Florence P Varodayan, Harpreet Sidhu, Max Kreifeldt, Marisa Roberto, Candice Contet
Excessive alcohol consumption in humans induces deficits in decision making and emotional processing, which indicates a dysfunction of the prefrontal cortex (PFC). The present study aimed to determine the impact of chronic intermittent ethanol (CIE) inhalation on mouse medial PFC pyramidal neurons. Data were collected 6-8 days into withdrawal from 7 weeks of CIE exposure, a time point when mice exhibit behavioral symptoms of withdrawal. We found that spine maturity in prelimbic (PL) layer 2/3 neurons was increased, while dendritic spines in PL layer 5 neurons or infralimbic (IL) neurons were not affected...
February 19, 2018: Neuropharmacology
Jesús Úbeda-Contreras, Ignacio Marín-Blasco, Roser Nadal, Antonio Armario
Regardless of its particular nature, emotional stressors appear to elicit a widespread and roughly similar brain activation pattern as evaluated by c-fos expression. However, their behavioral and physiological consequences may strongly differ. Here we addressed in adult male rats the contribution of the intensity and the particular nature of stressors by comparing, in a set of brain areas, the number of c-fos expressing neurons in response to open-field, cat odor or immobilization on boards (IMO). These are qualitatively different stressors that are known to differ in terms of intensity, as evaluated by biological markers...
February 15, 2018: Brain Structure & Function
Ling Shan, Hang-Yuan Guo, Corina N A M van den Heuvel, Joop van Heerikhuize, Judith R Homberg
AIMS: One potential risk factor for posttraumatic stress disorder (PTSD) involves the low activity (short; s) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR), possibly due to reduced prefrontal control over the amygdala. Evidence shows that DNA methylation/demethylation is crucial for fear extinction in these brain areas and is associated with neuronal activation marker c-Fos expression. We hypothesized that impaired fear extinction in serotonin transporter knockout (5-HTT-/- ) rats is related to changes in DNA (de) methylation and c-Fos expression in the prefrontal cortex (PFC) and/or amygdala...
February 9, 2018: CNS Neuroscience & Therapeutics
Gourango Talukdar, Ran Inoue, Tomoyuki Yoshida, Hisashi Mori
Syntenin-1 is a PDZ domain-containing intracellular scaffold protein involved in exosome production, synapse formation, and synaptic plasticity. We tested whether syntenin-1 can regulate learning and memory through its effects on synaptic plasticity. Specifically, we investigated the role of syntenin-1 in contextual and cued fear conditioning and extinction of conditioned fear using syntenin-1 knockout (KO) mice. Genetic disruption of syntenin-1 had little effect on contextual and cued fear memory. However, syntenin-1 KO mice exhibited selective impairment in cued fear extinction retention...
February 3, 2018: Neurobiology of Learning and Memory
X Du, K Serena, W Hwang, A M Grech, Y W C Wu, A Schroeder, R A Hill
Brain-derived neurotrophic factor (BDNF) is known to play a critical role early in the development of cortical GABAergic interneurons. Recently our laboratory and others have shown protracted development of specific subpopulations of GABAergic interneurons extending into adolescence. BDNF expression also changes significantly across adolescent development. However the role of BDNF in regulating GABAergic changes across adolescence remains unclear. Here, we performed a week-by-week analysis of the protein expression and cell density of three major GABAergic interneurons, parvalbumin (PV), somatostatin (SST) and calretinin (Cal) in the medial prefrontal cortex from prepubescence (week 3) to adulthood (week 12)...
February 2, 2018: Molecular and Cellular Neurosciences
Roger Marek, Jingji Jin, Travis D Goode, Thomas F Giustino, Qian Wang, Gillian M Acca, Roopashri Holehonnur, Jonathan E Ploski, Paul J Fitzgerald, Timothy Lynagh, Joseph W Lynch, Stephen Maren, Pankaj Sah
The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons in the IL eliminated vHPC-mediated inhibition...
February 5, 2018: Nature Neuroscience
Katharina M Hillerer, Barbara Woodside, Emily Parkinson, Hong Long, Silvanna Verlezza, Claire-Dominique Walker
In early lactation (EL), stressor salience modulates neuroendocrine stress responses, but it is unclear whether this persists throughout lactation and which neural structures are implicated. We hypothesized that this process is specific to EL and that the infralimbic (IL) medial prefrontal cortex (mPFC) might provide a critical link between assessment of threat and activation of the hypothalamo-pituitary-adrenal (HPA) axis in EL. We measured neuroendocrine responses and neuronal Fos induction to a salient (predator odor) or non-salient (tail pinch) psychogenic stressor in EL and late lactation (LL) females...
February 4, 2018: Stress: the International Journal on the Biology of Stress
Lucia Caffino, Giuseppe Giannotti, Giulia Messa, Francesca Mottarlini, Fabio Fumagalli
OBJECTIVES: Long-term abstinence following cocaine exposure up-regulates brain-derived neurotrophic factor (BDNF) expression in the mesocorticolimbic pathway. Given the increased vulnerability to drug abuse typical of adolescence, we hypothesized that changes in BDNF expression may become manifest early after the end of cocaine treatment in the adolescent brain. METHODS: Rats received cocaine injections from postnatal day 28 (PND28) to PND42 and the mesocorticolimbic expression of BDNF was measured by real-time PCR and Western blotting at PND43...
February 21, 2018: World Journal of Biological Psychiatry
Benjamin D Sachs, Ha L Tran, Emily Folse, Marc G Caron
The association between stress and mental illness has been well documented, but the molecular consequences of repeated exposure to stress have not been completely identified. The present study sought to elucidate the combinatorial effects of early life maternal separation stress and adult social defeat stress on alterations in signal transduction and gene expression that have been previously implicated in susceptibility to psychosocial stress. Molecular analyses were performed in the prelimbic/infralimbic cortex, amygdala, and nucleus accumbens, three brain regions that have been suggested to play critical roles in determining stress responses...
January 13, 2018: Neuroscience
Masoumeh Dadkhah, Payman Raise Abdullahi, Ali Rashidy-Pour, Hamid Reza Sameni, Abbas Ali Vafaei
The infralimbic (IL) cortex of the medial prefrontal cortex plays an important role in the extinction of fear memory. Also, it has been showed that both brain glucocorticoid and dopamine receptors are involved in many processes such as fear extinction that drive learning and memory; however, the interaction of these receptors in the IL cortex remains unclear. We examined a putative interaction between the effects of glucocorticoid and dopamine receptors stimulation in the IL cortex on fear memory extinction in an auditory fear conditioning paradigm in male rats...
January 9, 2018: Brain Research
Bing Huang, Youxing Li, Deqin Cheng, Guanhong He, Xing Liu, Lan Ma
Extinction learning of cocaine-associated contextual cues can help prevent cocaine addicts from relapsing. Pharmacological manipulation of β-adrenergic receptor (β-AR) during extinction learning is being developed as a potential strategy to treat drug addiction. We demonstrated that the extinction learning of cocaine-associated memory was mediated by β-arrestin2-biased but not heterotrimeric guanine nucleotide-binding protein (G protein)-dependent β-adrenergic signaling. We found that administration of the nonbiased β-AR antagonist propranolol, but not the G protein-biased β-AR antagonist carvedilol, blocked extinction learning of cocaine-conditioned place preference and the associated ERK activation in the infralimbic prefrontal cortex...
January 9, 2018: Science Signaling
Wesley N Wayman, John J Woodward
Abuse rates for inhalants among adolescents continue to be high, yet preclinical models for studying mechanisms underlying inhalant abuse remain limited. Our lab has previously shown that, in male rats, an acute binge-like exposure to toluene vapor that mimics human solvent abuse modifies the intrinsic excitability of medial prefrontal cortex (mPFC) pyramidal neurons projecting to the nucleus accumbens (NAc). These changes showed region (infralimbic; IL vs. prelimbic; PRL), layer (shallow; 2/3 vs. deep; 5/6), target (core vs...
January 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ankit Sood, Karina Chaudhari, Vidita A Vaidya
Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker...
January 10, 2018: Stress: the International Journal on the Biology of Stress
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