Synaptic homeostasis and synaptic maturation.

Virtually all developing neural circuitry undergoes at some point a spontaneous bursting activity called spontaneous network activity (or SNA): which in the spinal cord drives embryonic movements. We have determined that the normal levels of spinal SNA are maintained, in part, by compensatory changes in synaptic strength. In this way SNA acts to coordinate the maturation of excitatory and inhibitory synaptic strength. We are attempting to understand the mechanisms underlying synaptic homeostasis in vivo. The study has implications for conditions of hyperexcitability.

Synaptic refinement of an inhibitory interneuron.

Synaptic refinement is the developmental process whereby early projections are pruned back to form a more focused set of connections. The process has been studied extensively in excitatory projection neurons that map some part of the sensory world. We are studying synaptic refinement in an inhibitory interneuron that we have characterized in the embryonic spinal cord. We are currently testing the possibility that SNA drives this process. Errors in such a process could result in circuitry that has inappropriate levels and/or patterns of network activity.

Synaptic specificity.

Formation of specific connections in developing circuits is critical to proper behavioral output of those networks. We are studying molecules that may mediate the formation and specificity of these connections. These studies will provide insights into the hurdles that must be overcome when reconnecting an injured nervous system.