Genes, Neural Circuits, and Behavior

摘要 社交过程障碍是各种精神障碍的共同特征，如沟通障碍 精神障碍、自闭症谱系障碍、抑郁症和精神分裂症。尽管使用鼠标进行了广泛的研究 在模型和人脑成像方面，社交过程缺陷的潜在机制尚不清楚。 用ArpC3或Shank3小鼠进行的实验表明，这两个菌株的纯合子突变在社会生活中存在缺陷 行为。我们已经开发出一种系统，在这种系统中，选定的基因可以在特定的神经回路中被破坏 并有一些初步结果表明，前额叶皮质(PFC)到杏仁基底外侧核(BLA)的环路可以 调节社会行为。这项提议的总体目标是使用这种基于电路的新基因操作 确定ArpC3和Shank3突变小鼠中可能调节社会行为的神经回路的方法。 我们的中心假设是，PFC-BLA神经回路中的干扰会产生异常的社会行为。在……里面 目的#1我们将确定PFC-BLA回路是否是控制异常社会的常见神经通路 ArpC3和Shank3小鼠的行为学。目标#2将分析从PFC投射到两者的支路 BLA和VTA，并测试BLA和VTA中受体神经元在社会互动过程中的独特反应。 目标#3将专注于识别PFC-BLA电路下游可以调制的额外神经回路 社会进程。

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.