Medial prefrontal cortex

Accurate decision-making under imminent threat is critical to survival. However, arousal states, regulated by the neuromodulator norepinephrine, can cause both attentiveness and anxiety. Thus, adaptive decision making that scales with threat valence is crucial. To study proper decision-making under threat and the role of norepinephrine, we developed a novel task in which mice descend from a height toward an illusion of safe and unsafe visual cues. This virtual stimulus --- where there is a mismatch between actual safety and perceived safety --- relies on the evolutionarily conserved, innate fe

Short-term plasticity (STP) dynamically regulates synaptic strength on the timescale of milliseconds to seconds, playing a critical role in moment-to-moment information processing within neural circuits. Deficits in STP have been implicated in neurological and psychiatric disorders, but its precise contribution to higher cognitive functions and behavioral flexibility remains poorly understood. Here, we address this gap by focusing on synaptotagmin-7 (SYT7), a calcium sensor essential for facilitation---a form of STP in which high-frequency stimulation briefly enhances neurotransmitter release.

…control of social choice, such as the medial prefrontal cortex (mPFC). One potential, but unexplored role of the estrogen surge is to enable persistent neural states to facilitate costly behavio

Humans and other animals must sometimes “think outside the box” to discover better strategies that solve old problems under novel conditions, but how the metaphorical “box” itself constrains learning is unknown. In operant tasks, the mechanisms behind learning are often framed just in terms of reinforcing success or punishing failure, and any predisposed strategies for guiding actions are ignored. In ethological behaviors though, animals often have instinctive predispositions in how they approach an evolutionarily adapted task but can also learn new ways to do better. Combining chemogenetics,

…highly interconnected with the neocortex, encodes decision variables and aids in sustaining their representations in cerebral cor

Animals compose low-level actions in the service of high-level goals. Prefrontal cortex is essential for this organization when the goals are externally imposed, as in tasks where reward contingencies switch over time. Here we asked if it plays a similar role during spontaneous exploratory behaviors in the mouse. Using a hierarchical model, we identify stable patterns of action selection that capture emergent ‘task-states’ like wall following, object investigation or social interaction. These states align with distinct epochs of activity in medial prefrontal cortex (mPFC) – a coincidence that

…sulcus (IPS), anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC) in exploratory behaviors. However, the roles of these regions in signaling specific aspects of exploratory behaviors remain unclear. Based on earlier studies, we classified exploratory behaviors into two types driven by different motives: internal and external explorations. Internal exploration involves encountering options with uncertain outcomes and seeking in

Cognitive flexibility plays a key role in ensuring an individual's survival. The prefrontal cortex and striatum are both essential to cognitive flexibility but competing theories debate which structure among these two leads the role in detecting and representing new circumstances for a change, giving largely opposing predictions on neural activities in the prefrontal cortex and striatum during flexible behavior. We trained head-restrained mice to perform an action-outcome based dynamic foraging task and simultaneously recorded single-neuron activities in the medial prefrontal cortex (mPFC)

Rebound depolarization (RD) is a form of membrane depolarization triggered in some neurons following hyperpolarization. Typically, a series of action potentials are evoked during RD plateau. RD converts an inhibitory signal arriving to the neuron into an excitation signal, which is subsequently synaptically transmitted to other cells. The nature of RD in cortical neurons has been tested for several years without satisfactory explanation. The aim of our study was to evaluate the influence of adrenergic receptors activation in RD generation. Alpha-1, alpha-2, and beta-receptors have been tested.

…often occurring in the frontal cortex. FCDIIB is a common cause of pharmaco-resistant epilepsies and altered local neuronal activity has been reported in human FCDIIB tissue samples. Local cortical microcircuits are extensively modulated by monoaminergic axonal projections arising from the brain stem. Previous analysis of monoaminergic modulatory inputs in human FCDIIB biopsies suggested altered density and distrib

The medial prefrontal cortex (mPFC) is involved in cognitive and emotional functions housing neurons and astrocytes, impacting mPFC activity. To this end, astrocytes express several GPCR to fine-tune synaptic transmission such as CB1R and adenosine A1 and A2A receptors (A1R, A2AR). Since interactions of these receptors in astrocytes are not known, this work aims to fill the gap of the crosstalk between CB1R and adenosine receptors and their contribution for mPFC synaptic plasticity.CB1R-A1R and CB1R-A2AR complexes were observed in primary cultures of astrocytes, by using Proximation Ligation a

…The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) are essential for the consolidation of fear memories. This consolidation occurs in particular when BLA neurons responding to aversive stimuli are reactivated during non-REM sleep. However, the neural circuit mechanism during non-REM sleep remains unclear. We focus on the role of neocortical slow waves, a hallmark of non-REM sleep, in fear memory formation. By recording l

…such as hippocampus, striatum and prefrontal cortex. Nevertheless, the mechanism underlying depression remain elusive, and so, an effective treatment. To tackle this issue, cannabidiol (CBD) treatment has emerged as a

Binge eating disorder (BED) is the most prevalent eating disorder. Binge episodes are characterized by the consumption of a large amount of high-calorie food in a short period, accompanied by a sense of loss of control. BED is associated with comorbidities such as obesity and mood disorders. Several studies suggest that neuroinflammation occurs in reward-related brain circuit following bingeing on food high in sugar. In addition, preclinical studies in rat highlight cognitive consequences of binge-sucrose intake, affecting both anxiety levels and memory performance, with inconsistent results.

…of schizophrenia indicate that the medial prefrontal cortex (mPFC) is the main structure where PV neurons exhibit aberrant function. However, it is still

…phase shift of Bmal1 expression in the medial prefrontal cortex (mPFC) of a mouse model of depression (depression-like behavior and anhedonia induced by daily 10 min swim sessions for 5 consecutive days). Selective disruption of mPFC clockwork with viral Bmal1KO in CaMK2a excitatory neurons blocks the development of depressive-like phenotype in our model of depre

…electrophysiological recordings in the prefrontal cortex revealed compromised neuronal activity to some extent. The present study tested whether hearing loss would lead to altered expression of the GABA and dopamine (DA) systems in key re

Introduction: Early life stress (ELS) significantly increases predisposition to depression. Here, we examined whether the restoring effects of treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597, which elevates anandamide levels, are associated with alterations in microRNAs (miRNAs) related with depression and whether specific miRNAs have a crucial role in the antidepressant-like effect of URB597. Methods: In experiment 1, male rats were exposed to ELS using the "Limited Bedding and Nesting" paradigm from postnatal day (P)7 to P14. During P45 to P60 (late-adolescence), URB59

Navigating space to retrieve uncued rewards at remembered locations depends on intact hippocampal function. Indeed, learning novel reward locations in familiar environments requires synaptic plasticity and lasting reorganization of spatial representations in the CA1 area of the dorsal hippocampus. Such reorganization is absent when learning associations between rewards and non-spatial cues, for which spatial memory is not involved. Thus, the rodent brain selectively adjusts weights of hippocampal inputs, plasticity processes, and the stability of spatial representations, supporting adaptive be

…The medial prefrontal cortex (mPFC) is a key integration hub within the associative recognition memory circuit as it receives long range excitatory inputs from the nucleus reuniens (NRe) and intermediate hippocampus (iCA1), both pathways being critical for learning. Inhibitory interneurons play essential roles in spatial and working memory function by gating signal flow and sculpting microcircuit d

…that undergo massive PCD in the cortex include the first wave of oligodendrocyte precursor cells (firstOPCs) and most of GABAergic interneurons, which die postnatally within the same period. Furthermore, firstOPCs and most interneurons share common embryonic origins. Here we investigated how PCD of both firstOPCs and their lineage-related interneurons impact behavior and cortical networks. We used behavioral assays, patch-clamp recordings and immunostainings in two mouse models in

Metabolic Associated Fatty Liver Disease (MAFLD) has recently emerged as a major health concern in Western countries, being characterized by hepatic fat accumulation, altered metabolism, increased oxidative stress, and inflammation. This condition triggers the release of hormones, free radicals, and inflammatory mediators in blood, potentially affecting central nervous system. Unfortunately, limited studies have explored the impact of MAFLD on the brain and its potential association with neuronal metabolism and activity. In our study, we utilized preclinical MAFLD model induced by a six-week e

Neuroactive steroids such as allopregnanolone that act as a positive allosteric modulator of synaptic and extrasynaptic δ-subunit-containing GABAA receptors, has shown antidepressant effects on depressive symptoms in both clinical and preclinical studies. However, the neuronal dynamics associated with these effects are still unknown. In the present study, we discovered that allopregnanolone, but not the benzodiazepine diazepam, has antidepressant-like effects in the social interaction test (SIT) of social defeat stress (SDS) model mice by decreasing intervals of repetitive social interaction (

The Ventral Tegmental Area (VTA) is a crucial component of the brain's reward system and is known to regulate motivated behaviour. Recent studies have shown that activation of VTA dopaminergic (DA) neurons can stimulate anti-bacterial and anti-tumour immunity, suggesting a potential link between mental states and an organism's immune response to disease. However, the specific mechanisms underlying these peripheral effects are still unclear. Given that VTA-DA neurons project to multiple brain regions, and each pathway promote different behaviour we considered that also the immune effects of eac