CAREER - Maturation of Synaptic Properties During Early Postnatal Development.

Wright State University, Dayton OH

Investigators

Abstract

The brain and spinal cord function through networks of neurons that communicate with each other at specialized sites called synapses. Generally speaking, synaptic inputs are divided into excitatory and inhibitory. Unchecked excitation provokes the breakdown of processing capabilities (as in an epileptic seizure) and frequently drives the postsynaptic neuron to death (i.e. excitotoxicity). Too much inhibition will silence the neuron. The awardee will explore how neurons adjust the strength of their inhibitory synapses to counteract particular patterns of excitatory input. The model system is the Renshaw cell, a spinal cord interneuron that provides feedback recurrent inhibition over motoneuron output. This interneuron receives major excitatory input from motor axon collaterals inside the spinal cord. They also express a specialized complement of inhibitory glycinergic synapses characterized by very large postsynaptic receptor fields that we have hypothesized increase their strength. The awardee will analyze the structural and functional maturation of glycinergic synapses on Renshaw cells during the first postnatal month using anatomical and electrophysiological techniques. These data will then be related to the development of the connection between motor axons and Renshaw cells and the expression of cholinergic receptors that mediate function at these synapses. Finally, a relationship will be sought between the development of the excitatory and inhibitory synapses by attempting to block the former using Botulinum toxin-A at various developmental stages. It is expected that the results will provide insights into mechanisms that could explain the unique characteristics of glycinergic synapses on Renshaw cells. Extension of these results to other neurons in the brain might provide clues on how individual neurons adjust the strength of their inhibitory inputs in conjunction with the excitatory input that they aim to counteract. This research program will be used by the Principal Investigator to introduce research topics and techniques to a variety of undergraduate, Masters level and Ph.D. students. A series of postgraduate lectures in synaptic mechanisms will also be developed to fill a need in postgraduate education at Wright State University.