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

控制社会行为的前额叶回路的经验依赖性成熟

• 批准号: 9980495
• 负责人: Hirofumi Morishita
• 金额: $ 52.35万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-18 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980495
• 关键词: Action Potentials; Acute; Adolescent; Adult; Affect; Animals; Behavior; Calcium; Cells; Childhood; Coupled; Dimensions; Disease; Electrophysiology (science); Exhibits; Female; Fiber; Frequencies; Goals; Image; Interneurons; Measures; Medial; Mediating; Mental disorders; Monitor; Motor Activity; Mus; Neurodevelopmental Disorder; Neurons; Photometry; Play; Population; Positioning Attribute; Prefrontal Cortex; Process; Pyramidal Cells; Shapes; Signal Transduction; Slice; Social Behavior; Social Controls; Social Interaction; Social isolation; Somatostatin; Source; Structure of paraventricular nucleus of thalamus; Synapses; Techniques; Technology; Testing; Thalamic structure; Wireless Technology; anxiety-related behavior; base; cell type; experience; hippocampal pyramidal neuron; improved; in vivo; inhibitory neuron; insight; male; novel; optogenetics; p65; patch clamp; preference; recruit; relating to nervous system; reward circuitry; sensory cortex; social; social deficits; therapeutic target

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.

儿童时期的社会经验对于成人前额叶皮层（PFC）正常功能的建立至关重要。