Richard Tsien

Honors and Awards

• Member, National Academy of Sciences (1997)
• Bauer Lectureship, Brandeis University (March 2007)
• MERIT Award, National Institutes of Mental Health (July 2004)
• Member, Institute of Medicine of the National Academy of Sciences (1994)
• Kaiser Award for Outstanding and Innovative Teaching, Stanford University (1991, 1995, 1999)

Postdoctoral Advisees

Patrick Bader , Rachel Groth , Yulong Li , Hyokeun Park , Damon Poburko , Michael Tadross

Graduate & Fellowship Program Affiliations

• Molecular and Cellular Physiology
• Neurosciences

Web Site Links

• http://www-leland.stanford.edu/group/MCP

Research Interests

We are studying how the location and identity of presynaptic calcium channels is regulated. Voltage-gated Ca2+ channels provide the critical link between the firing of a presynaptic nerve terminal and its release of neurotransmitter. The Ca2+ channels must be positioned very close to sites of vesicle fusion, and come in diverse forms with distinct activity-dependence, responsiveness to GABA, dopamine, acetylcholine and other neuromodulators, and susceptibility to neurological disorders such as migraine, ataxia or dystonia. Our working hypothesis involves molecular “slots” for particular types of channels. Slots regulate the mix of channel types and also help explain how defective channels might displace normal ones in genetically dominant disorders.

Our lab is particularly interested in studying multiple modes of synaptic vesicle fusion. The opening of Ca2+ channels drives at least two distinct forms of fusion. In the classical mode, the vesicle membrane fully merges with and flattens into the presynaptic membrane (“full collapse fusion”). In a newly characterized mode, termed “kiss-and-run” the connection between the vesicle interior and the external medium lasts long enough to allow passage of neurotransmitter, but the connection is severed before the identity of the vesicle is lost. We study the dynamic properties and functional implications of both fusion modes by loading single synaptic vesicles with single photoluminescent reporter particles—quantum dots. Sharp distinctions between full collapse fusion and kiss-and-run are now in hand. Experiments are underway to monitor the same fusion event optically and electrophysiologically.

One area of intense attention in our lab is the fundamental unit of cell-cell communication between brain neurons: quantal synaptic transmission. Presynaptic release of a packet of neurotransmitter, for example, glutamate, causes activation of postsynaptic receptors and a brief flow of current that promotes firing of...

Publications

• The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles. Zhang Q, Li Y, Tsien RW. Science. 2009; 323 (5920): 1448-53
• Uncoupling dendrite growth and patterning: single-cell knockout analysis of NMDA receptor 2B. Espinosa JS, Wheeler DG, Tsien RW, Luo L. Neuron. 2009; 62 (2): 205-17
• CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation-transcription coupling. Wheeler DG, Barrett CF, Groth RD, Safa P, Tsien RW. J Cell Biol. 2008; 183 (5): 849-63
• A role for retinoic acid in homeostatic plasticity. Groth RD, Tsien RW. Neuron. 2008; 60 (2): 192-4
• The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. Barrett CF, Tsien RW. Proc Natl Acad Sci U S A. 2008; 105 (6): 2157-62