Synaptic Competition Between Inhibitory Intracortical Synapses

9726944 Turrigiano哺乳动物中枢神经系统的大部分发育是在出生后发生的，需要经验才能形成功能回路。神经生物学中的一个中心问题是阐明经验以模式神经活动的形式决定哪些突触连接保持，哪些突触失去的规则。一个重要的假设是神经元之间以一种依赖活动的方式相互竞争以建立突触连接。这被认为是通过突触之间竞争一种对维持突触至关重要的神经营养剂的数量而发生的。成功刺激突触后神经元的突触前神经元获得更多的神经营养物质，因此胜过那些不成功的神经元。尽管这一模型已经引起了人们的极大兴趣，但它还没有得到直接测试。皮质回路既有抑制性突触连接，也有兴奋性突触连接。抑制性连接，即突触前神经元的电活动抑制突触后神经元的电活动，对于皮质回路的正常功能是必不可少的，但尽管如此重要，迄今为止大多数研究几乎都集中在阐明兴奋性突触连接形成的规则上。虽然抑制性连接的形成规则尚未建立，但对这些规则的理解对于理解皮质环路的起源至关重要。特里吉亚诺博士的研究项目的目的是询问抑制性突触连接的形成是否涉及竞争机制，以及这种竞争是否通过依赖活性的营养剂摄取而发生。这些实验将有助于完成我们对神经回路发育的理解，并将测试一个关于哺乳动物中枢神经系统活动如何连接的重要模型。

9726944 TURRIGIANO Much of the development of the mammalian central nervous system occurs after birth, and requires experience in order for functional circuits to form. A central problem in neurobiology has been to elucidate the rules by which experience, in the form of patterned neural activity, determines which synaptic connections are maintained and which are lost. An important hypothesis is that neurons compete with each other in an activity-dependent manner for the establishment of synaptic connections. This is thought to occur through competition between synapses for limiting quantities of a neurotrophic agent that is essential for maintenance of the synapse. Presynaptic neurons that are successful at exciting the postsynaptic neuron obtain more neurotrophic agent and therefore out-compete neurons that are not. Although this model has generated much interest, it has not yet been directly tested. Cortical circuits have both inhibitory and excitatory synaptic connections. Inhibitory connections, where electrical activity in a presynaptic neuron inhibits electrical activity in the postsynaptic neuron, is essential for the proper functioning of cortical circuits, but despite this importance most research to date has concentrated almost exclusively on elucidating the rules by which excitatory synaptic connections are formed. While the rules for formation of inhibitory connections have not been established, an understanding of these rules is crucial for understanding the genesis of cortical circuits. The goal of Dr. Turrigiano's research project is to ask whether the formation of inhibitory synaptic connections involves competitive mechanisms, and to ask whether this competition occurs through the activity-dependent uptake of a trophic agent. These experiments will help to complete our understanding of neural circuit development, and will test a prominent model for how activity wires up the mammalian central nervous system.