Chinfei Chen MD, PhD
Assistant Professor of Neurology
Harvard Medical School/Children's Hospital
Department of Neurology (Neuroscience)

MRRC Project(s)

Research Description

The formation of precise synaptic connections in the developing central nervous system (CNS) is essential for neurological function. After the initial mapping of a neuron to its target, there is marked rearrangement of the connections, during which some inputs are strengthened while others are eliminated. The mechanisms by which this process of synaptic refinement and maturation occur are not well delineated. A powerful model system for the study of synaptic remodeling can be found at the connection between the retina and the dorsal lateral geniculate nucleus (LGN), the retinogeniculate synapse. Our previous studies have characterized, using electrophysiological techniques, the normal developmental sequence of remodeling at this connection in a mouse LGN brain slice preparation. Using the normal developmental sequence of physiologic changes at this synapse for comparison, we are identifying and characterizing the mechanisms involved in the refinement of the retinogeniculate synapses. Both the role of neuronal activity and specific molecules are being examined by a number of approaches. First, we are altering neuronal activity in vivo using pharmacological and genetic tools. Second, we are screening various mutant mice to identify specific molecules involved in synaptic remodeling. Candidate molecules include those associated with axon guidance cues, growth factors, and cell signaling. Finally, we are developing an in vitro culture system that recapitulates many aspects of synaptic remodeling found in vivo. With this system we can screen for novel molecules and factors involved in synaptic remodeling. Elucidation of the mechanisms underlying developmental synaptic remodeling will be important in the understanding of neurological disorders that result from aberrant connections, such as some forms of epilepsy and mental retardation.

Publications

Chen C, Regehr W. The mechanism of cAMP-mediated enhancement at a cerebellar synapse. J Neurosci 1997; 17: 8687-8694.

Chen C, Regehr W. Contributions of residual calcium to fast synaptic transmission. J Neurosci 1999; 19:6257-6266.

Chen C, Regehr W. Developmental remodeling of the retinogeniculate synapse. Neuron 2000; 28:955-966.

Contact Information

Chinfei Chen - Ph: - 617-355-8137; Fax: - 617-738-1542

Mac Hooks, graduate student
Ellie Edson, graduate student
Xiaojin Liu, postdoctoral fellow
Chris Testa, technician
Angela Chen, technician