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Neuroscience Graduate Program at UCSF

Faculty - Roger Nicoll, M.D.

The Cellular and Molecular Basis of Synaptic Plasticity

Research Description

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.

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Current Projects

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

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Lab Members

Meryl Horn, Graduate Student
Jonathan Levy, Graduate Student
Samantha Ancona Esselmann, Graduate Student
Kate Lovero, Graduate Student
Salvatore Incontro, Postdoctoral Fellow
Bruce Herring, Postdoctoral Fellow
Quynh Anh Nguyen, Graduate Student
Nenyin Sheng, Postdoctoral Fellow

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Selected Publications

Link to Publications via PubMed

Incontro, S., Asensio, C.S., Edwards, R.H., and Nicoll, R.A.: Efficient, complete deletion of synaptic proteins using CRISPR. Neuron. 83:1051-7 (2014).

Shipman, S.L., Herring, B.E., Suh, Y.H., Roche, K.W. and Nicoll, R.A.: Distance-dependent scaling of AMPARs is cell-autonomous and GluA2 dependent. J. Neurosci. 33:13312-12219 (2013).

Lu, W., Bushong E.A., Shih, T.P., Ellisman, M.H. and Nicoll, R.A.: The cell-autonomous role of excitatory synaptic transmission in the regulation of neuronal structure and function. Neuron 78:433-439 (2013).

Herring, B.E., Shi, Y., Suh, Y.H., Schmid, S.M., Roche, K.W., and Nicoll, R.A.: Cornichon proteins determine the subunit composition of synaptic AMPARs. Neuron 77:1083-1096 (2013).

Granger, A.J., Shi, Y., Lu, W., Cerpas, M., and Nicoll, R.A.: LTP requires a reserve pool of glutamate receptors independent of subunit type. Nature (Article) 493:495-500 (2013).

Shipman, S.L. and Nicoll, R.A.: A subunit specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Neuron 76:309-316 (2012).

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).

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Roger Nicoll, M.D.





Office Address

UCSF MC 2140
Genentech Hall, room N-272D
600 16th Street
San Francisco, CA 94143-2140

Other Websites

Lab Website

Cellular and Molecular Pharmacology

Institute for Neurodegenerative Diseases

PIBS Website

The Wheeler Center for the Neurobiology of Addiction