Advances in Development and Function of Neural Circuits and Behavior

神经回路和行为的发育和功能的进展

• 批准号: 10023660
• 负责人: Hirofumi Morishita
• 金额: $ 5.93万
• 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/10023660
• 关键词: Action Potentials; Acute; Adolescent; Adult; Affect; Animals; Behavior; Calcium; Cells; Childhood; Coupled; Development; Dimensions; Disease; Electrophysiology (science); Exhibits; Female; Fiber; Frequencies; Goals; Image; Interneurons; Measures; Medial; Mediating; Mental disorders; Monitor; Motor Activity; Mus; Neurodevelopmental Disorder; Neurons; Neurophysiology - biologic function; Photometry; Play; Population; Positioning Attribute; Prefrontal Cortex; Process; Pyramidal Cells; Shapes; Signal Transduction; Slice; Social Behavior; 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; neural circuit; 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.

童年时期的社会经验对于成年前额叶皮层（PFC）的正常功能至关重要。 以及相关的行为，包括社会行为，这是一个跨物种的基本过程。但具体 经历社会经验依赖性成熟以调节社会行为的回路 明白鉴于社会过程缺陷是许多神经发育和 精神疾病，识别对经验依赖性调制敏感的特定回路将指向 治疗目标，允许改善社会处理缺陷共享的范围内， 紊乱本研究的目的是阐明社会经验背后的PFC电路机制， 依赖性成熟对调节适当的社会行为至关重要。在小鼠中，幼年的社会隔离导致成年 社交行为缺陷和伴随皮质下投射的深层内侧PFC（mPFC）缺陷 锥体神经元在各种皮层下靶点中，我们的初步研究确定了边缘丘脑 它接收信号并将信号中继到经典奖励电路的各个组件， mPFC的突出投射目标，优先被社会互动招募。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，并增加了它们的抑制性驱动。各个 类型的抑制性神经元，深层抑制性神经元的一个选择性亚类，已知对 振荡皮层下投射的深层皮层神经元是唯一表现出升高的群体， 青少年社会隔离后的兴奋性。这个项目将测试假设，青少年的社会经验- mPFC深层投射神经元向边缘丘脑的依赖性成熟及深部脑电的调节 mPFC层抑制性神经元驱动mPFC和边缘丘脑的协调活动，以有效地调节 社会行为我们将通过整合技术来测量（纤维光度成像， 膜片钳/体内电生理学）和操纵（光遗传学/化学遗传学）选择性的活性。 在老鼠的社会行为中的回路。