Synapses are the essential point of contact between neurons and their targets for the directional flow of information in the nervous system. The study of how synapses form and how they function is fundamental to our understanding of nervous system connectivity and communication. It is now believed that deficiencies in synaptic function are central to many psychiatric and neurodegenerative diseases such as schizophrenia, Alzheimer’s, Parkinson’s and Huntington’s disease. Thus, it is anticipated that a better understanding of the molecular mechanisms that control these highly specialized structures holds great promise for the development of urgently needed, novel therapies for these diseases.
The principle research objective of my laboratory is to elucidate the cellular and molecular mechanisms underlying the formation, stability, and elimination of CNS synapses. We primarily utilize cultured hippocampal neurons as a model system, and extend these studies to genetically modified mouse models when appropriate. Fundamental questions addressed in the lab include; 1) how does cell-cell contact result in the assembly of pre- and postsynaptic compartments, 2) what are the contributions of pre- and postsynaptic elements to the integrity of the synapse, 3) what are the transsynaptic signals that regulate synaptic plasticity, and 4) is synapse elimination a stereotypical process and, if so, what is the sequence of molecular events underlying synapse disassembly?
Answers to these questions will not only reveal mechanisms underlying developmental and neurodegenerative disorders, but will also provide insight into the molecular signals involved in synaptic strengthening, a process believed essential for learning and memory.