The Development of Spontaneous Synchronized Activity in Mouse Cerebral Cortex

哺乳动物的大脑可以说是所有生物中最复杂的器官，它的1000多亿个神经元和它们之间的几万亿个连接是如何发展起来的，在很大程度上仍然是一个谜。PIS和其他研究人员已经证明，大脑发育的基本特征之一是发生自发的电波活动，这些电波在大脑中的大型结构中传播，并允许发育中的神经元相互通信。PI的实验室使用应用于小鼠大脑的光学和电生理学方法来研究这些自发波是如何在适当的发育阶段在大脑中启动的。拟议的实验旨在证明特定群体的起搏器神经元启动这些波，并且这些起搏器群体在早期发育过程中发生变化。起搏器特性的这种变化被认为允许活动波发生在比单一起搏器类型更长的发育时期。这些研究的预期结果是要了解：(1)在发育的每个阶段，哪些神经元充当自发活动的起搏器；(2)起搏器之间的转换是如何发生的；以及(3)这种转换是否涉及胚胎大脑的一种学习形式。人脑自发活动波的中断很可能是许多大脑发育临床异常的原因，了解活动是如何启动的，应该能让我们深入了解这些疾病涉及的基本机制。该项目将为学习发育神经科学的研究生提供良好的培训机会。

The mammalian brain is arguably the most complex organ of any living being, and how its more than 100 billion neurons and several trillion connections among them develop remains largely a mystery. The PIs and other researchers have shown that one of the essential features of brain development is the occurrence of spontaneous waves of electrical activity that propagate across large structures in the brain and which serve to allow developing neurons to communicate with each other. The PI's laboratory uses optical and electrophysiological methods applied to the mouse brain to study how these spontaneous waves are initiated in the brain at the appropriate stages of development. The proposed experiments aim to show that specific populations of pacemaker neurons initiate these waves, and that these pacemaker populations change during early development. This change in pacemaker identity is thought to allow waves of activity to occur over longer periods of development than would be possible with a single pacemaker type. The expected results of these studies are to understand: (1) which neurons serve as pacemakers for spontaneous activity at each stage of development; (2) How the transition between pacemakers occurs; and (3) whether this transition involves a form of learning by the embryonic brain. Disruptions of spontaneous waves of activity in the human brain is likely to be the cause of many clinical abnormalities of brain development, and understanding how activity is initiated should allow us to gain insights into the basic mechanism involved in such ailments. This project will provide outstanding training opportunities for graduate students studying developmental neuroscience.