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
Seth Shipman, Graduate Student
Jonathan Levy, Graduate Student
Yun Shi, Postdoctora Fellow
John Gray, Postdoctoral Fellow
Adam Granger, Graduate Student
Kate Lovero, Graduate Student
Alexander Jackson, Postdoctoral Fellow
Bruce Herring, Postdoctoral Fellow
Quynh Anh Nguyen, Graduate Student
Maya Yamazaki , Postdoctora Fellow
Nenyin Sheng, Postdoctoral Fellow
Granger, A.J., Shi, Y., Lu, W., Cerpas, M., and Nicoll, R.A.: LTP requires a pool of extrasynaptic glutamate receptors independent of subunit type. Nature (in revision).
Shipman, S.L. and Nicoll, R.A.: A subunit specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Neuron (in press).
Gray, J.A., Shi, Y., Usui, H., During, M.J., Sakimura, K., and Nicoll, R.A.: Distinct modes of AMPA receptor suppression at developing synapses by GluN2A and GluN2B: analysis of single-cell GluN2 subunit deletion in vivo. Neuron 71:1085-1101 (2011).
Jackson, A.C., Milstein, A.D., Soto, D., Farrant, M., Cull-Candy, S.G. and Nicoll, R.A.: Probing TARP modulation of AMPA receptor conductance with polyamine toxins. J. Neurosci. 31:7511-7520 (2011).
Shipman, S.L., Schnell, E., Hirai, T., Chen, B.S., Roche, K.W., and Nicoll, R.A.: Functional dependence of neuroligin on a novel, non-PDZ intracellular domain. Nat. Neurosci. 14:718-726 (2011).
Jackson, A.C. and Nicoll, R.A.: The Expanding Social Network of Ionotropic Glutamate Receptors: TARPs and Other Transmembrane Auxiliary Subunits. Neuron 70:178-199 (2011).
Goold, C.P. and Nicoll, R.A.: Single-Cell Optogenetic Excitation Drives Homeostatic Synaptic Depression. Neuron 68:512-528 (2010).
Shi, Y., Lu, W., Milstein, A.D. and Nicoll, R.A.: The stoichiometry of AMPA receptors and TARPs varies by neuronal cell type. Neuron 62:633-640 (2009).
Lu, W., Shi, Y., Jackson, A.C., Bjorgan, K., During, M.J. Sprengel, R., Seeburg, P.H., and Nicoll, R.A.: Subunit composition of AMPA receptors revealed by a single-cell genetic approach. Neuron 62:254-268 (2009).
Roger Nicoll, M.D.
UCSF MC 2140
Genentech Hall, room N-272D
600 16th Street
San Francisco, CA 94143-2140