The brain is especially vulnerable to environmental influences during the perinatal period. While the effects of environmental factors are usually studied in isolation, it is more typical to be exposed to multiple influences during early development, necessitating study of synergistic actions on the developing brain. Both maternal infection and endocrine disrupting phthalates can decrease cell number in the medial prefrontal cortex (mPFC), a region critical for executive functioning. In the present study, groups of pregnant Long Evans rats were treated with either (1) 100 μg/kg (i.p.) lipopolysaccharide (LPS) on embryonic days 15 and 16 combined with a low-dose (1 mg/kg) phthalate mixture throughout gestation and the neonatal period, (2) LPS alone, (3) phthalates alone, or (4) neither phthalates nor LPS (control). Neurons and glial cells were stereologically quantified in the mPFC. The adult offspring previously exposed to LPS or phthalates alone had reduced mPFC neuron number in exposed males, but not females, while the combination treatment did not produce significant effects. In males, LPS alone also reduced the number of glia in the mPFC. Additionally, the combination of LPS and phthalates resulted in fewer pregnancies to term and decreased litter size. These results provide insight into how common environmental factors can interact to alter the developmental trajectory of the mPFC.

The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are synchronously activated during social fear expression. Moreover, optogenetic inhibition of the mPFC-LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal-habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear. These results unravel a crucial role of the prefrontal-habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptom often observed in many psychiatric disorders.

Chronic stress leads to hypofunction of the medial prefrontal cortex (mPFC), mechanisms of which remain to be determined. Enhanced activation of GABAergic of parvalbumin (PV) expressing interneurons (INs) is thought to play a role in stress-induced prefrontal inhibition. In this study, we tested whether chemogenetic inhibition of mPFC PV INs after chronic stress can rescue chronic stress-related behavioral and physiological phenotypes. Mice underwent 2 weeks of chronic variable stress (CVS) followed by a battery of behavioral tests known to be affected by chronic stress exposure, e.g. an open field (OF), novel object recognition (NOR), tail suspension test (TST), sucrose preference test (SPT), and light dark (LD) box. Inhibitory DREADDs were actuated by 3 mg/kg CNO administered 30 min prior to each behavioral test. CVS caused hyperactivity in the OF, reduced sucrose preference in the SPT (indicative of enhanced anhedonia), and increased anxiety-like behavior in the LD box. Inhibition of PV IN after stress mitigated these effects. In addition, CVS also resulted in reduced thymus weight and body weight loss, which were also mitigated by PV IN inhibition. Our results indicate that chronic stress leads to plastic changes in PV INs that may be mitigated by chemogenetic inhibition. Our findings implicate cortical GABAergic INs as a therapeutic target in stress-related diseases.

Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (Δ9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.

Addiction is a complex behavioral disorder characterized by compulsive drug-seeking and drug use despite harmful consequences. The prefrontal cortex (PFC) plays a crucial role in cocaine addiction, involving decision-making, impulse control, memory, and emotional regulation. The PFC interacts with the brain\'s reward system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc). The PFC also projects to the lateral habenula (LHb), a brain region critical for encoding negative reward and regulating the reward system. In the current study, we examined the role of PFC-LHb projections in regulating cocaine reward-related behaviors. We found that optogenetic stimulation of the PFC-LHb circuit during cocaine conditioning abolished cocaine preference without causing aversion. In addition, increased c-fos expression in LHb neurons was observed in animals that received optic stimulation during cocaine conditioning, supporting the circuit\'s involvement in cocaine preference regulation. Molecular analysis in animals that received optic stimulation revealed that cocaine-induced alterations in the expression of GluA1 subunit of AMPA receptor was normalized to saline levels in a region-specific manner. Moreover, GluA1 serine phosphorylation on S845 and S831 were differentially altered in LHb and VTA but not in the PFC. Together these findings highlight the critical role of the PFC-LHb circuit in controlling cocaine reward-related behaviors and shed light on the underlying mechanisms. Understanding this circuit\'s function may provide valuable insights into addiction and contribute to developing targeted treatments for substance use disorders.

There are mutual neural projections between the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC),which form a circuit.Recent studies have shown that this circuit is vital in regulating arousal from sleep and general anesthesia.This paper introduces the anatomical structures of VTA and mPFC and the roles of various neurons and projection pathways in the regulation of arousal,aiming to provide new ideas for further research on the mechanism of arousal from sleep and general anesthesia.
腹侧被盖区(VTA)与内侧前额叶皮层(mPFC)之间存在相互神经投射,并形成环路,近年来的研究显示该环路在睡眠与全身麻醉的觉醒调控中发挥着重要的作用。本文通过对VTA与mPFC的解剖结构、二者中的各种神经元及投射通路在觉醒调控过程中的作用进行综述,期望为睡眠觉醒与全身麻醉机制研究提供新的思路。.

While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here, extracellular recordings in awake mice revealed that over half of studied mPFC neurons showed photosensitivity, that was diminished by inhibition of intrinsically photosensitive retinal ganglion cells (ipRGCs), or of the upstream thalamic perihabenular nucleus (PHb). In 15% of mPFC photosensitive neurons, firing rate changed monotonically along light-intensity steps and gradients. These light-intensity-encoding neurons comprised four types, two enhancing and two suppressing their firing rate with increased light intensity. Similar types were identified in the PHb, where they exhibited shorter latency and increased sensitivity. Light suppressed prelimbic activity but boosted infralimbic activity, mirroring the regions\' contrasting roles in fear-conditioning, drug-seeking, and anxiety. We posit that prefrontal photosensitivity represents a substrate of light-susceptible, mPFC-mediated functions, which could be ultimately studied as a therapeutical target in psychiatric and addiction disorders.

Environmental sustainability is characterized by a conflict between short-term self-interest and longer-term collective interests. Self-control capacity has been proposed to be a crucial determinant of people\'s ability to overcome this conflict. Yet, causal evidence is lacking, and previous research is dominated by the use of self-report measures. Here, we modulated self-control capacity by applying inhibitory high-definition transcranial current stimulation (HD-tDCS) above the left dorsolateral prefrontal cortex (dlPFC) while participants engaged in an environmentally consequential decision-making task. The task includes conflicting and low conflicting trade-offs between short-term personal interests and long-term environmental benefits. Contrary to our preregistered expectation, inhibitory HD-tDCS above the left dlPFC, presumably by reducing self-control capacity, led to more, and not less, pro-environmental behavior in conflicting decisions. We speculate that in our exceptionally environmentally friendly sample, deviating from an environmentally sustainable default required self-control capacity, and that inhibiting the left dlPFC might have reduced participants\' ability to do so.

Sporting experience plays a pivotal role in shaping exercise habits, with a mutually reinforcing relationship that enhances cognitive performance. The acknowledged plasticity of cognition driven by sports necessitates a comprehensive examination. Hence, this study delves into the dynamic intricacies of the prefrontal cortex, exploring the impact of orienteering experience on cognitive performance. Our findings contribute empirical evidence regarding the functional activation of specific brain regions bridging the nexus between experiential factors and cognitive capabilities. In this cross-sectional study, a cohort of forty-nine athletes was enrolled to meticulously examine behavioral variances and prefrontal cortex dynamics among orienteering athletes of varying experience levels across diverse non-specialized scenarios. These investigations involved the utilization of functional near-infrared spectroscopy (fNIRS) to detect alterations in oxygenated hemoglobin (HbO2). The high-experience expert group exhibited neurological efficiency, demonstrating significantly diminished brain activation in the dorsolateral prefrontal, left ventral lateral prefrontal, and right orbitofrontal regions compared to the low-experience group. Within the low-experience novice group, superior performance in the spatial memory task was observed compared to the mental rotation task, with consistently lower reaction times across all conditions compared to the high-experience group. Notably, cerebral blood oxygenation activation exhibited a significant reduction in the high-experience expert group compared to the low-experience novice group, irrespective of task type. The dorsolateral prefrontal lobe exhibited activation upon task onset, irrespective of experience level. Correct rates in the spatial memory task were consistently higher than those in the mental rotation task, while brain region activation was significantly greater during the mental rotation task than the spatial memory task.\" This study elucidates disparities in prefrontal cortex dynamics between highly seasoned experts and neophyte novices, showcasing a cognitive edge within the highly experienced cohort and a spatial memory advantage in the inexperienced group. Our findings contribute to the comprehension of the neural mechanisms that underlie the observed cognitive advantage and provide insights into the forebrain resources mobilized by orienteering experience during spatial cognitive tasks.\"

How human prefrontal and insular regions interact while maximizing rewards and minimizing punishments is unknown. Capitalizing on human intracranial recordings, we demonstrate that the functional specificity toward reward or punishment learning is better disentangled by interactions compared to local representations. Prefrontal and insular cortices display non-selective neural populations to rewards and punishments. Non-selective responses, however, give rise to context-specific interareal interactions. We identify a reward subsystem with redundant interactions between the orbitofrontal and ventromedial prefrontal cortices, with a driving role of the latter. In addition, we find a punishment subsystem with redundant interactions between the insular and dorsolateral cortices, with a driving role of the insula. Finally, switching between reward and punishment learning is mediated by synergistic interactions between the two subsystems. These results provide a unifying explanation of distributed cortical representations and interactions supporting reward and punishment learning.