Experience-dependent maturation of prefrontal circuitry in control of social behavior

点击翻译按钮获取中文摘要

Social experience during childhood is essential to establish proper function in the adult prefrontal cortex (PFC) and related behaviors including social behavior, a fundamental process across species. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. Given that social process deficit is a common dimension of many neurodevelopmental and psychiatric disorders, identifying the specific circuits sensitive to experience-dependent modulation will point toward therapeutic targets that allow amelioration of social processing deficits shared across of range of disorders. The objective of this study is to elucidate the PFC circuit mechanisms underlying social experience- dependent maturation crucial to mediate proper social behavior. In mice, juvenile social isolation leads to adult social behavior deficits and accompanies deficits in sub-cortically projecting deep layer medial PFC (mPFC) pyramidal neurons. Among various sub-cortical targets, our preliminary study identified the limbic thalamus which receives and relays signals to various components of the classical reward circuitry, as the most prominent projection target from mPFC that is preferentially recruited by social interaction. Importantly, juvenile social isolation reduced excitability of this projection neuron and increased their inhibitory drive. Among various types of inhibitory neurons, a selective subclass of deep layer inhibitory neuron, known to be essential to oscillate subcortically projecting deep layer cortical neurons, were the only population that exhibited elevated excitability after juvenile social isolation. This project will test the hypothesis that juvenile social experience- dependent maturation of deep layer mPFC projection neurons to limbic thalamus and its modulation by deep layer mPFC inhibitory neurons drives coordinated activity in mPFC and limbic thalamus to effectively modulate social behavior. We will test this hypothesis by integrating techniques to measure (fiber photometry imaging, patch-clamp/ in vivo electrophysiology) and manipulate (optogenetics/chemogenetics) the activities of selective circuits during social behavior in mice.