Influence of Synaptic Inhibition on the Development of Neuronal Function

在大脑发育的早期，神经细胞之间的突触联系或强或弱。这个过程在很大程度上取决于这些突触在发育过程中的使用，它显然导致了感觉和运动系统的最佳功能。在这方面，兴奋性突触，如肌肉细胞的突触，已经得到了很好的研究。相比之下，我们对抑制性突触的发育知之甚少。抑制性突触，顾名思义，是用来减少中枢神经系统的活动的。我们以前已经表明，抑制性突触活动影响中枢听觉系统的结构和功能发育。例如，突触抑制的丧失会导致树突形状的改变和突触强度的改变。本研究旨在研究抑制性突触发挥这些强大作用的机制。特别是，我们将研究一种抑制性递质受体甘氨酸受体的作用，以及当甘氨酸在突触释放时，氯离子和碳酸氢盐两种离子渗透膜的作用。这些研究的结果将有助于我们深入了解中枢抑制性连接的发展和可塑性。

9630544 PI: Sanes During early brain development, the synaptic contacts between nerve cells become stronger or weaker. This process depends in large part upon the use of these synapses during development, and it apparently leads to optimal function of sensory and motor systems. In this regard, excitatory synapses, such as those at muscle cells, have been well studied. In contrast, we know relatively little about the development of inhibitory synapses which, as their name implies, serve to decrease activity in the central nervous system. We have previously shown that inhibitory synaptic activity influences the structural and functional development in the central auditory system. For example, loss of synaptic inhibition leads to changes in dendrite shape and changes in the strength of synapses. The present proposal seeks to study the mechanisms whereby inhibitory synapses exert these strong effects. In particular, we will examine the contribution of an inhibitory transmitter receptor, the glycine receptor, and the role of two ions that permeate the membrane when glycine is released at the synapse, chloride and bicarbonate. The results from these studies should provide insight into the development and plasticity of central inhibitory connections.