Synapses are fundamental units of neuronal connectivity in the brain. It is at these specialized cell junctions that neurons communicate with one another. Many neuroscientists now look to the synapse for principles of learning and memory, for processes underlying behavior, and for pathogenic mechanisms of various neurological diseases. Our long-term goal is to understand the mechanisms regulating the development and function of synapses and to probe the roles of synaptic and circuitry dysfunction in certain abnormal behaviors and their relevance to neuropsychiatric disorders.
There are currently three major aspects of research in the lab. First, we are interested in the molecular mechanisms regulating the assembly and function of the postsynaptic complex. Although hundreds of proteins have been identified at the postsynaptic complex, little is known about their in vivo functions at synapses. Using genetic approaches in mice we are dissecting the roles of some key synaptic proteins in the assembly, maintenance and plasticity of the postsynaptic complex (see Feng et al., 1998, Science 282:1321-1324; Parker et al., 2004, J. Neurosci. 24:378-88; Lu et al., 2007, J. Cell Biol. 177:1077-1089).
The second aspect of our research is focused on using genetic approaches in mice to dissect the molecular and cellular basis of behavior. We are particularly interested in how changes in synaptic and circuitry function may lead to abnormal behaviors and their implications in neuropsychiatric disorder. We apply a variety of mouse molecular genetic methods, such as inducible knockout mice and regional and cell type-specific knockout and transgenic mice, to elucidate the molecules, the types of neurons, and the circuits involved in generating specific behaviors (see Welch et al., 2007, Nature 448:894-900).
The third line of research in the lab is to develop cutting edge genetic tools for probing synaptic and circuitry function and dysfunction in mice. These include transgenic mice that express GFP in single neurons in the brain for long-term live imaging; single-neuron labeling with inducible cre-mediated knockout (SLICK) in transgenic mice for combined genetic manipulation and imaging in single neurons in the brain; and Channelrhodopsin-2 transgenic mice for light-induced activation and mapping of neural circuits in living mice (see Feng et al., 2000, Neuron 28:41-51; Young and Feng, 2004, Curr Opin Neurobiol. 14:642-646; Arenkiel, et al., 2007, Neuron 54:205-218; Wang et al., 2007, PNAS 104:8143-8148).
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