Dynamic connectivity in neocortical networks

 描述（由申请人提供）：在感觉和感知期间以及在网络活动的背景下，突触如何在其原生环境中发挥作用，对于理解它们如何传输信息以及如何通过经验进行修改至关重要。传统上，电生理学研究是在与完整大脑完全不同的实验条件下进行的，其中最关键的区别之一是急性脑切片中几乎不存在背景活动。因此，在不同的大脑状态下，活跃的皮层回路中的神经元之间的功能连接仍然是未知的。我们建议调查兴奋性突触的性质，而不是孤立的，但它们的功能嵌入在一个动态的神经网络，使用在体外和体内记录。分析将集中在啮齿动物躯体感觉皮层（哺乳动物新皮层的一个典型例子）表层中的锥体神经元对之间的单个突触连接。我们的初步数据表明，在高网络活动的条件下，兴奋性突触连接到多种神经元细胞类型可以有效地沉默GABAb激活。我们将确定负责这种抑制的GABA的细胞来源，并研究GABAb信号是如何在体内调节的。了解新皮层中突触连接的静态和动态模式对于了解健康和疾病中的回路功能和可塑性至关重要。

 DESCRIPTION (provided by applicant): How synapses function in their native environment, during sensation and perception and in the context of network activity, are critical to understanding how they can transmit information and be modified by experience. Traditionally, electrophysiological studies have been carried out under experimental conditions that are profoundly different from the intact brain, where one of the most critical differences is the near absence of background activity in acute brain slices. Thus, the functional connectivity between neurons in active cortical circuits, across different brain states, remains unknown. We propose to investigate the properties of excitatory synapses, not in isolation, but as they function embedded in a dynamic neural network, using both in vitro and in vivo recordings. Analysis will focus on individual synaptic connections between pairs of pyramidal neurons in superficial layers of the rodent somatosensory cortex, a well-characterized exemplar of the mammalian neocortex. Our preliminary data indicates that under conditions of high network activity, excitatory synaptic connections onto multiple neuronal cell types can be effectively silenced by GABAb activation. We will identify the cellular source of GABA responsible for this suppression and examine how GABAb signaling is regulated in vivo. Understanding both the static and dynamic patterns of synaptic connectivity in the neocortex will be essential for understanding circuit function and plasticity in health and disease.