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

儿童时期的社会经验对于成人前额叶皮质(PFC)的正常功能的建立至关重要。 以及包括社会行为在内的相关行为，这是跨物种的基本过程。然而，具体的 依赖社会经验的成熟来规范社会行为的电路很差 明白了。鉴于社会过程缺陷是许多神经发育和 精神障碍，识别对经验依赖调制敏感的特定电路将指向 朝着能够改善社会加工缺陷的治疗目标迈进 精神错乱。这项研究的目的是阐明社会经验背后的PFC回路机制。 依赖成熟对于调节适当的社会行为至关重要。在小鼠中，青少年社交孤立导致成年 社会行为缺陷及其伴发的皮层下投射深层内侧PFC(MPFC) 锥体神经元。在各种皮质下靶点中，我们的初步研究确定了边缘丘脑。 它接收信号并将其转发到经典奖励电路的各种组件，因为 来自mPFC的突出投影目标，优先通过社交招募。重要的是，青少年 社会隔离降低了这种投射神经元的兴奋性，增加了它们的抑制性驱动力。在众多 抑制神经元的类型，深层抑制神经元的一个选择性亚类，已知对 震荡的皮质下投射的深层皮质神经元是唯一表现出升高的群体 青少年社交隔离后的兴奋性。这个项目将检验青少年社会经验的假设-- 边缘丘脑深层mPFC投射神经元的依赖成熟及深部对其调节作用 层mPFC抑制神经元驱动mPFC和边缘丘脑的协调活动以有效地调制 社交行为。我们将通过将技术集成到测量(光纤光度成像， 膜片钳/体内电生理学)和操纵(光遗传学/化学遗传学)选择性 在小鼠的社会行为过程中的回路。

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.