Abstract
The ventral portion of the medial prefrontal cortex (vmPFC) regulates mood, sociability, and context-dependent behaviors. Consequently, altered vmPFC activity has been implicated in the biological basis of emotional disorders. Recent methodological advances have greatly enhanced the ability to investigate how specific prefrontal cell populations regulate mood-related behaviors, as well as the impact of long-term stress on vmPFC function. However, emerging preclinical data identify prominent sexual divergence in vmPFC behavioral regulation and stress responsivity. Notably, the rodent infralimbic cortex (IL), a vmPFC subregion critical for anti-depressant action, shows marked functional divergence between males and females. Accordingly, this review examines IL encoding and modulation of mood-related behaviors, including coping style, reward, and sociability, with a focus on sex-based outcomes. We also review how these processes are impacted by prolonged stress exposure. Collectively, the data suggest that chronic stress has sex-specific effects on IL excitatory/inhibitory balance that may account for sex differences in the prevalence and course of mood disorders.
Highlights
Negative mood states are a feature of numerous psychiatric conditions, including anxiety and depressive disorders
Chemogenetic activation of infralimbic cortex (IL) PV interneurons induces anxietylike behavior only in females. These results indicate that estrogen is protective for female IL glutamatergic neurons, sex differences in chronic stress effects are projection-dependent, and interneuron populations are more susceptible to chronic stress in females
Less work has examined stress coping in females, but IL glutamate neurons have sexually divergent effects on physiological stress responses
Summary
Negative mood states are a feature of numerous psychiatric conditions, including anxiety and depressive disorders. While pharmacological and lesion studies have linked IL activity with depression-relevant behaviors, advances in cell-type specificity have identified sex-dependent roles in stress, reward, and social processes. Activation of male IL glutamatergic neurons 24 h before testing reduces FST passive coping (Fuchikami et al, 2015), suggesting IL stimulation induces pyramidal neuron plasticity.
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