Synaptic integration in the periaqueductal grey circuit of defensive behaviour

神经科学中的主要挑战之一是理解神经电路如何在行为过程中执行计算。例如，传入的感觉信息是如何转化为适当的行为输出的？回答这个问题需要详细了解单个神经元是如何处理信息并将突触输入转换为动作电位输出的。神经元接受大量的突触输入到树突上，最近的体外实验表明，树突在突触输入到达动作电位起始点之前对突触输入进行预处理。这种计算的独立实现应该允许活体中的单个神经元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回路中的突触整合，并分析中脑导水管周围灰质(PAG)中的单个神经元如何参与导致防御性冻结行为的计算。PAG是包括下丘脑和杏仁核在内的一个大型网络的一部分，它是指导防御行为的上行和下行信息汇聚的共同路径。与执行更高认知功能的细胞相比，PAG神经元的结构更简单，但有一个突出的树状树，有少量的分支。PAG中的神经元激活是实施防御反应的关键一步，但人们对PAG神经元放电的原因知之甚少。通过结合行为学、遗传学、电生理学和光学技术，我旨在解决三个具体问题：(1)在防御行为中激活的PAG神经元如何整合兴奋信号？(2)抑制性突触如何设定PAG神经元的兴奋性水平？(3)杏仁核的激活如何调节PAG神经元在冰冻行为中激活的输入-输出转换？这项关于PAG中树突整合的研究结果将促进我们对对执行基本行为至关重要的电路中的神经元如何处理信息和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.