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.
