Synaptic integration in the periaqueductal grey circuit of defensive behaviour

防御行为的导水管周围灰色回路中的突触整合

• 批准号: 259603355
• 负责人: Dr. Sabine Rühle
• 金额: --
• 依托单位: Sainsbury Wellcome Centre
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/259603355?language=en
• 关键词: Synaptic; integration; periaqueductal; grey; circuit

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.

神经科学的主要挑战之一是了解神经回路如何在行为过程中实现计算。例如，传入的感官信息如何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换为动作电位输出。神经元在其树突树上接收大量突触输入，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对其进行预处理。这种独立的计算实现应该允许体内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的大型网络的一部分，并充当引导防御行为的上升和下降信息汇聚的共同路径。与执行更高认知功能的细胞相比，PAG 神经元具有更简单的结构，但具有突出的树突树和少量分支。 PAG 中的神经元激活是实施防御反应的关键步骤，但对于驱动 PAG 神经元放电的原因知之甚少。通过结合行为、遗传、电生理和光学技术，我的目标是解决三个具体问题：（1）PAG 神经元在防御行为期间如何激活整合兴奋信号？ (2)抑制性突触如何设定PAG神经元的兴奋水平？ (3) 杏仁核的激活如何调节冻结行为期间活跃的 PAG 神经元的输入输出转换？这项关于 PAG 中树突整合的研究结果将加深我们对电路中神经元如何处理信息和产生防御反应的理解，这些神经元对于实现基本行为至关重要。

项目成果

Ultrafast tissue staining with chemical tags

• DOI: 10.1073/pnas.1411087111
• 发表时间: 2014-09-09
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Kohl, Johannes;Ng, Julian;Jefferis, Gregory S. X. E.
• 通讯作者: Jefferis, Gregory S. X. E.