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Genes, Neural Circuits, and Behavior

基因、神经回路和行为

基本信息

批准号：
10159753
负责人：
Il Hwan Kim
金额：
$ 38.08万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-18 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10159753
关键词：
Amygdaloid structure Anxiety Axon Behavior Behavioral Biological Assay Brain Brain imaging Cells Characteristics Communication impairment Complex Electrophysiology (science)Foundations Gene Deletion Gene Mutation Genes Goals Halorhodopsins Human Impairment Interneurons Knock-in Knock-in Mouse Knock-out Knockout Mice Knowledge Label Mental Depression Mental disorders Methods Monitor Morphology Mus Mutant Strains Mice Names Neural Pathways Neurons Optics Pathogenicity Pathway interactions Pattern Prefrontal Cortex Reporting Research Research Domain Criteria Schizophrenia Series Social Behavior Social Controls Social Interaction Social Processes Social support Synapses Synaptic Cleft System Testing Therapeutic Intervention Ventral Tegmental Area Vertebral column Work autism spectrum disorder base endophenotype excitatory neuron experimental study genetic approach genetic manipulation in vivo mouse model mutant neural circuit neural network novel reconstitution relating to nervous system response restoration risk variant selective expression social social deficits

项目摘要

ABSTRACT Impaired social processes are a common feature in diverse psychiatric disorders such as communication disorders, autism-spectrum disorder, depression, and schizophrenia. Despite extensive studies using mouse models and human brain imaging, the mechanisms underlying deficiencies in social processes are obscure. Experiments with ArpC3 or Shank3 mice reveal that homozygous mutants from both strains are deficient in social behavior. We have developed a system where selected genes can be disrupted within a specific neural circuit and have some preliminary results that a prefrontal cortex (PFC) to basolateral amygdala (BLA) circuit can modulate social behavior. The Overall Goal of this proposal is to use this novel circuit-based gene manipulation approach to identify neural circuits in the ArpC3 and Shank3 mutant mice that may regulate social behaviors. Our Central Hypothesis is that disturbances in a PFC-BLA neural circuit produce abnormal social behaviors. In Aim #1 we will determine whether the PFC-BLA circuit is a common neural pathway controlling abnormal social behavior in ArpC3 and Shank3 mice. Aim #2 will analyze the collateral circuit projecting from the PFC to both BLA and VTA, and test the distinctive responses of recipient neurons in the BLA and VTA during social interaction. Aim #3 will focus on identifying additional neural circuits downstream of the PFC-BLA circuit that can modulate social processes.

抽象的社交过程受损是多种精神疾病（例如沟通障碍）的共同特征障碍、自闭症谱系障碍、抑郁症和精神分裂症。尽管使用小鼠进行了大量研究模型和人脑成像，社会过程缺陷的潜在机制尚不清楚。使用 ArpC3 或 Shank3 小鼠进行的实验表明，这两种品系的纯合突变体均缺乏社交能力行为。我们开发了一种系统，可以在特定的神经回路中破坏选定的基因并有一些初步结果表明前额皮质（PFC）到基底外侧杏仁核（BLA）回路可以调节社会行为。该提案的总体目标是使用这种新颖的基于电路的基因操作方法来识别 ArpC3 和 Shank3 突变小鼠中可能调节社会行为的神经回路。我们的中心假设是 PFC-BLA 神经回路的紊乱会产生异常的社会行为。在目标 #1 我们将确定 PFC-BLA 回路是否是控制异常社交的常见神经通路 ArpC3 和 Shank3 小鼠的行为。目标 #2 将分析从 PFC 投射到两者的并行电路 BLA 和 VTA，并测试 BLA 和 VTA 中受体神经元在社交互动过程中的独特反应。目标 #3 将重点关注识别 PFC-BLA 电路下游的额外神经电路，这些神经电路可以调节社会进程。