Crosstalk between inhibitory and excitatory neurotransmitter systems during synapse development in the brain

突触是大脑中神经元交流的关键部位。它们是高度专业化的结构，具有复杂的分子机制，使化学神经传递过程得以发生。最近的证据表明，通过神经递质GABA发出早期信号可能有助于塑造大脑的连通性。然而，这一过程背后的分子和细胞事件仍然知之甚少。在这项发现拨款提案中，我们将面临关于早期GABA信号的功能及其在调节突触连接中的作用的几个悬而未决的问题。首先，我们将使用先进的分子操作、高分辨率共聚焦显微镜和电生理学技术来确定早期GABA传递如何控制谷氨酸突触的形成。我们的初步数据表明，通过神经递质GABA发出的早期信号控制着发育中的海马神经元上兴奋性突触的数量。接下来，我们将监测神经元上GABA突触的发育，并确定它们与谷氨酸突触发育的关系。最后，我们将研究控制早期GABA信号的分子和细胞过程。这一发现资助项目将为对了解大脑回路发展感兴趣的学生提供极好的概念和技术培训。这些学生产生的数据还将为控制突触形成过程的机制创造新的见解。

Synapses are key sites of neuronal communication in the brain. They are highly specialized structures with complex molecular machinery that enables the process of chemical neurotransmission to occur. Recent evidence suggests that early signaling through the neurotransmitter GABA, may serve to sculpt brain connectivity. However, the molecular and cellular events that underlie this process remain poorly understood. In this Discovery Grant proposal, we will confront several unresolved issues with respect to the function of early GABA signaling and its role in regulating synaptic connectivity. First, we will determine how early GABA transmission controls glutamate synapse formation using advanced molecular manipulations, high resolution confocal microscopy, and electrophysiology techniques. Our preliminary data suggests that early signaling through the neurotransmitter GABA controls the number of excitatory synapses on developing hippocampal neurons. Next, we will monitor the development of GABA synapses on neurons and define their relationship to developing glutamate synapses. Finally, we will investigate the molecular and cellular processes that govern early GABA signaling. This Discovery Grant project will provide excellent conceptual and technical training for students interested in understanding the development of brain circuitry. The data produced by these students will also create novel insight into mechanisms that control the process of synapse formation.