Our laboratory is interested in understanding the molecular mechanisms that underlie neuronal plasticity. Plasticity is the property of the nervous system that enables it to undergo long-lasting, sometimes permanent adaptive responses to brief stimuli. The process of plasticity is believed to be 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 disease and Alzheimer 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 such as the influx of extracellular calcium or neurotrophin application regulates synaptic function through gene transcription. As we identify pathway components, we manipulate their function within neurons to better understand the role that these molecules play in plasticity. In a complementary approach, we are studying how a mutation in a single gene leads to memory disturbances and neurodegeneration in the neurological disorder, Huntington's disease. We have developed a cellular model of the disease that has allowed us to manipulate the mutant gene to better understand the relationship between its structure and function.

We use multiple approaches to study mechanisms of neuronal plasticity and neurodegeneration. Molecular biology and biochemistry techniques are used 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.