Craig C. Garner

Title
Professor

Department
Psychiatry and Behavioral Sciences
Neurology

Research Interests
Cellular and molecular mechanisms of synapse assembly and function.

Email
cgarner@stanford.edu

Phone
723-4942

Fax
498-7761

Address
1201 Welch Road, Rm P106
Mail Code: 5485

http://garnerlab.stanford.edu/

Faculty Research Description
We are interested in understanding the fundamental cellular and molecular mechanisms that guide the formation, maintenance and elimination of excitatory synapses in the vertebrate CNS. To accomplish these goals, we use molecular and genetic approaches to identify key structural and regulatory proteins of glutamatergic synapses. In recent years, we have used these tools to address basic questions concerning nascent synapse formation. For example, what is the time frame of synapse formation? Which forms first, the presynapse or the postsynapse? What are the cellular mechanisms of assembly? Are synapses formed via the sequential recruitment of individual components or as ensembles? Once assembled what is the half-life of a synapse, how does this relate to the turnover rates of individual components, and does neuronal/synaptic activity modulate synapse life? Answers to these questions are coming from classical biochemistry to purify cellular organelles that carry synaptic proteins to and from the synapse as well as from live cell imaging to follow the dynamics of these proteins.

We are also interested in understanding how synaptic dysfunction in mouse models of Down syndrome contributes to cognitive impairment. Initial studies indicate that, as with individuals with Down syndrome, mice carrying an extra copy of the Down syndrome critical region have cognitive and learning problems. Abnormal synaptic signaling between neuronal cells appears to be one possible underlying cause. Future studies will seek to define the responsible genes and whether drugs that alter synaptic signaling can correct these deficits. Intense research in this area will hopefully lead to practical treatments for cognitive dysfunction in individuals with Down syndrome

Müller BM, Kistner U, Veh RW, Cases-Langhoff C, Becker B, Gundelfinger ED, Garner CC, Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein. J. Neurosci. 15(3):2354-2366, 1995.

Cases-Langhoff, C, B. Voss, A.M. Garner, U. Appeltauer, B.M. Müller, K. Takei, U. Kistner, R.W. Veh, P. De Camilli, E.D. Gundelfinger and C.C. Garner. Piccolo a novel component of the cytomatrix anchoring synaptic vesicles to the presynaptic plasmalemma. Eur. J. Cell Biol. 69:214-223, 1996.

Fenster S.D., W.J. Chung, R. Zhai, C. Cases-Langhoff, B. Voss, A,.M. Garner, U. Kaempf, S. Kindler, E.D. Gundelfinger and C.C. Garner. Piccolo, a presynaptic zinc finger protein structurally related to bassoon. Neuron, 25(1), 203-214, 2000.

Friedmon, H.V., T. Bresler, C.C. Garner, and N. Ziv. The assembly dynamics of individual excitatory synapses in cultured of rat hippocampal neurons. Neuron, 27:57-69, 2000.

Wu, H., Reissner, C., Kuhlendahl, S., Coblentz, B.W., Reuver, S., Kindler, S., Gundelfinger, E.D. and C.C. Garner. Intramolecular interactions regulate SAP97 binding to GKAP. EMBO J. 19: 1-12, 2000.

Ziv, N.E., Garner, C.C. Principles of glutamatergic synapse formation: seeing the forest for the trees. Curr. Opin. Neurobiol. 11(5): 536-43. 2001.

Shapira, M., R. G. Zhai, et al. (2003). "Unitary assembly of presynaptic active zones from Piccolo-Bassoon transport vesicles." Neuron 38(2): 237-52.

Montgomery, J., Zamorano, P. and Garner, C.C. MAGUKs in Synaptic Plasticity: An emerging View. Cell Mol. Life. Sci 61: 911-29 (2004).

Ziv NE, and Garner CC. Cellular and molecular mechanisms of presynaptic assembly. Nat Rev Neurosci 5: 385-99, (2004).

Areas of Study
Cellular Neurobiology
Developmental Neuroscience
Synaptogenesis
Down syndrome
Neuronal Excitability