Synaptic integration in the periaqueductal grey circuit of defensive behaviour

神经科学的主要挑战之一是理解神经回路如何在行为过程中实现计算。例如，如何将传入的感官信息转化为适当的行为输出？回答这个问题需要详细了解单个神经元如何处理信息并将突触输入转化为动作电位输出。神经元在树突树上接收大量的突触输入，最近的体外实验表明树突在突触输入到达动作电位起始位点之前就对其进行了预处理。这种独立的计算实现应该允许个体神经元在体内执行高度复杂的信息处理。在这个项目中，我的目标是研究小鼠防御行为背后的突触整合电路，并分析导水管周围灰质（PAG）中的单个神经元如何促进导致防御冻结行为的计算。PAG是包括下丘脑和杏仁核在内的一个大网络的一部分，是指导防御行为的上升和下降信息汇聚的共同路径。与执行高级认知功能的细胞相比，PAG神经元的结构更简单，但其树突树的分支数量较少。PAG神经元的激活是防御反应实现的关键步骤，但鲜为人知是什么驱使PAG神经元放电。通过结合行为学、遗传学、电生理学和光学技术，我的目标是解决三个具体问题：(1)在防御行为中活跃的PAG神经元如何整合兴奋信号？(2)抑制性突触如何调节PAG神经元的兴奋性水平？(3)杏仁核的激活如何调节冻结行为中活动的PAG神经元的输入-输出转换？这项关于PAG树突整合的研究结果将促进我们对神经元如何在执行基本行为的关键电路中处理信息并产生防御反应的理解。

One of the main challenges in Neuroscience is to understand how neural circuits implement computations during behaviour. For example, how is incoming sensory information transformed into the appropriate behavioural output? Answering this question requires detailed knowledge on how individual neurons process information and convert synaptic input into action potential output. Neurons receive a plethora of synaptic inputs onto their dendritic tree, and recent in vitro experiments have shown that dendrites pre-process synaptic input before it reaches the action potential initiation site. This independent implementation of computations should allow individual neurons in vivo to perform highly complex information processing. In this project, I aim to investigate synaptic integration in a circuit underlying defensive behaviour in the mouse, and analyse how single neurons in the periaqueductal grey (PAG) contribute to the computations leading to defensive freezing behaviour. The PAG is part of a large network that includes the hypothalamus and the amygdala, and acts as a common path where ascending and descending information directing defensive behaviour converges. PAG neurons have a simpler structure compared to cells carrying out higher cognitive functions, yet have a prominent dendritic tree with a small number of branches. Neuronal activation in the PAG is a crucial step in the implementation of defensive responses, but little is known about what drives PAG neurons to fire. By combining behavioural, genetic, electrophysiological and optical techniques, I aim to address three specific questions: (1) How do PAG neurons active during defensive behaviour integrate excitatory signals? (2) How do inhibitory synapses set the excitability level of PAG neurons? (3) How does activation of the amygdala modulate the input-output transformation of PAG neurons active during freezing behaviour? The results of this study on dendritic integration in the PAG will advance our understanding of how neurons in a circuit critical for implementing basic behaviours process information and generate defensive responses.