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Neuroscience Graduate Program at UCSF
The Cellular and Molecular Basis of Synaptic Plasticity
My lab is interested in elucidating the cellular and molecular mechanisms underlying learning and memory in the mammalian brain. Long-term potentiation (LTP), a phenomenon in which brief repetitive activity causes a long lasting (many weeks) enhancement in the strength of synaptic transmission, is generally accepted to be a key cellular substrate for learning and memory. My lab uses a combination of electrophysiological and molecular techniques to elucidate the molecular basis of LTP. We have found that LTP involves the rapid activity-dependent trafficking of glutamate receptors to the synapse. This trafficking requires the interaction of two families of synaptic proteins. One family is a novel group of proteins that, we discovered which bind to glutamate receptors and act as auxiliary subunits. These proteins are not only essential for the trafficking of the glutamate receptors, but also control the gating of the receptor channel. The other family is comprised of a family of scaffolding proteins that bind to the auxiliary subunits and thereby anchor the receptors at the synapse. Much of the current work in the lab is focused on how activity controls this receptor trafficking and how the increase in synaptic strength during LTP is stabilized and maintained.
AMPA receptor subunits in receptor trafficking
MAGUK scaffolding proteins in anchoring synaptic AMPA receptors
Conditional knock out mice to explore the role of synaptic proteins in glutamate receptor trafficking
TARPs control of AMPA receptor gating
Activity dependent trafficking of NMDA receptors
Guillermo Elias, Graduate Student
Carleton Goold, Graduate Student
Alexander Jackson, Postdoctora Fellow
Geoffrey Kerchner, Postdoctoral Fellow
Wei Lu, Postdoctoral Fellow
Aaron Milstein, Graduate Student
Anastassios Tzingounis, Postdoctoral Fellow
Link to Publications via PubMed
Nicoll, R.A., Tomita, S., and Bredt, D.S.: Auxiliary subunits assist AMPA-types glutamate receptors. Science (Review) 311:1253-1256 (2006).
Tomita, S., Adesnik, H., Sekiguchi, M., Zhang, W., Wada, K., Howe, J.R., Nicoll, R.A., and Bredt, D.S.: Stargazin modulates AMPA rece ptor gating and trafficking by different domains. Nature (Article) 435:1052-1058 (2005).
Fukata, Y., Adesnik, H., Iwanaga, T., Bredt, D.S., Nicoll, R.A., and Fukata, M.: Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulates synaptic transmission. Science 313:1792-1795 (2006).
Tzingounis, T.V. and Nicoll, R.A.: Arc/arg3.1: linking gene expression to synaptic plasticity and memory. Neuron 52:403-408 (2006).
Adesnik, H. and Nicoll, R.A.: Conservation of GluR2-containing AMPA receptors during LTP. J. Neurosci. 27:4598-4602 (2007).
Elias, G.M., Funke, L., Stein, V., Grant, S.G., Bredt, D.S., and Nicoll, R.A.: Synapse specific and developmentally regulated targeting of AMPA receptors by a family of MAGUK scaffolding proteins. Neuron 52:307-320 (2006).
Elias, G.M. and Nicoll, R.A.: Synaptic trafficking of glutamate receptors by MAGUK scaffolding proteins. Trends in Cell Biol. 17:343-352 (2007).
Kato, A.S., Zhou, W.,Milstein, A.D., Knierman, M.D., Siuda, E.R., Dotzlaf, J.E., Yu, H., Hale, J.E., Nisenbaum, E.S., Nicoll, R.A., and Bredt, D.S.: New TARP isoform, g-7, differentially regulates AMPA receptors. J. Neurosci. 27:4969-4977 (2007).
Tzingounis, A.V., Kobayashi, M., Takamatsu, K., and Nicoll, R.A.: The diffusible calcium sensor, hippocalcin, gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal neurons. Neuron 53:487-493 (2007).
Milstein, A.D. Zhou, W., Karimzadegan, S. Bredt, D.S. and Nicoll, R.A.: TARP subtype and stoichiometry control AMPA receptor gating. Neuron 55:905-918 (2007).
Bellone, C. and Nicoll, R.A.: Rapid bidirectional switching of synaptic NMDA receptors. Neuron 55:779-785 (2007).
Menuz, K.A. Stroud, R.M., Nicoll, R.A. and Hays, FA.: TARPs convert AMPA receptor antagonists into agonists. Science (in press).
Roger Nicoll, M.D.
Phone
415-476-2018
Physical Address
Genentech Hall
600 16th Street
N-272D
Mission Bay Campus
Mailing Address
UCSF, Genentech Hall 600 16th Street
Box 2140
San Francisco, CA 94143-2140
For Internal Campus Mail
Box 2140
Other Websites
Cellular and Molecular Pharmacology