Molecular Mechanisms of Synaptic Plasticity and Neurodegeneration
Our laboratory is interested in understanding the molecular mechanisms that underlie neuronal plasticity and those that lead to certain neurodegenerative diseases. Plasticity is the property of the nervous system that enables it to undergo long-lasting, sometimes permanent adaptive responses to brief stimuli, and it is important for establishing precise patterns of synaptic connections during early neuronal development and for learning and memory in older animals. Disturbances in plasticity and synaptic function could contribute significantly to memory disorders characteristic of some neurodegenerative diseases such as Huntington’s, Parkinson’s, and Alzheimer’s disease.
We are focusing on two problems related to plasticity. Work from several laboratories has suggested that brief stimuli lead to lasting adaptive responses in part through changes in new gene expression. We aim to elucidate the signal transduction pathways by which specific stimuli regulates synaptic function through gene transcription. We also aim to understand how new gene products get delivered to the specific synapses undergoing plasticity. During the course of this work, we have focused on particular genes, such as Arc, that are critical for memory consolidation. Recently, we have discovered a new kinase that is under the control of key glutamate receptors, which regulates AMPAR trafficking, neuronal gene transcription, synaptic plasticity and learning. We use multiple approaches to study mechanisms of neuronal plasticity and neurodegeneration. We use molecular biology and biochemistry techniques to identify and manipulate molecules that are involved in these processes and electrophysiology and imaging techniques to test the effects of these manipulations and to understand the roles of these molecules in synaptic structure and function. In selected cases, we make transgenic mice to study the effects of these pathways in vivo using behavior, physiology, imaging and histology.
Academic community service and committee membership:
Gladstone mentoring and management committee, Gladstone Scientific Executive commuter, Department of neurology junior faculty mentor