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Stephen Rayport, M.D., Ph.D.

Associate Professor

E-mail: sgr1@columbia.edu

Synaptic Actions of Mesoaccumbens Dopamine Neurons:

rayport picture Ventral tegmental area dopaminergic neurons project to the nucleus accumbens where they appear to mediate the rewarding effects of abused drugs as well as positive symptoms in schizophrenia. We are examining their synaptic actions using two strategies. In the presynaptic strategy, we aim to elucidate the synaptic actions of individual dopamine neuron varicosities. Recent findings from this laboratory have shown that dopamine neurons in cell culture release glutamate as a co-transmitter from a subset of their synapses. Using transgenic mice with fluorescent dopamine neurons, we are now examining dopamine neuron synaptic actions in the brain slice using multiphoton microscopy and patch recording. The presence of glutamate as a cotransmitter suggests that dopamine neuron synapses may have novel neuroplastic capabilities. To address the functional role of colocalized glutamate, we are making transgenic mice where glutaminase, the enzyme that produces neurotransmitter glutamate, is selectively deleted from dopamine neurons. One prediction is that these mice will have less propensity to develop drug dependence. In the postsynaptic strategy, we aim to identify important actions of dopamine on accumbens neurons. In cell culture, we have shown that the GABAergic synapses made by accumbens neurons with each other are potently modulated by dopamine. We plan to extend these studies to accumbens brain slices using multiphoton microscopy, calcium imaging and patch recording. The hope here is that reversing psychostimulant-induced plastic changes will provide new means to treat drug dependence and potentially offer insight into the pathogenesis of schizophrenia.

Selected publications
Joyce MP, Rayport S (2000) Mesoaccumbens dopamine neuron synapses reconstructed in vitro are glutamatergic. Neuroscience 99:445-456.

Wong AC, Shetreat ME, Clarke JO, Rayport S (1999) D1- and D2-like dopamine receptors are colocalized on the presynaptic varicosities of striatal and nucleus accumbens neurons in vitro. Neuroscience 89:221-233.

Sulzer D, Joyce MP, Lin L, Geldwert D, Haber SN, Hattori T, Rayport S (1998) Dopamine neurons make glutamatergic synapses in vitro. Journal of Neuroscience 18:4588-4602.

Shetreat ME, Lin L, Wong AC, Rayport S (1996) Visualization of D1 dopamine receptors on living nucleus accumbens neurons and their colocalization with D2 receptors. Journal of Neurochemistry 66:1475-1482.

Shi W-X, Rayport S(1994) GABA synapses formed in vitro by local axon collaterals of nucleus accumbens neurons. Journal of Neuroscience 14:4548-4560.

Stephen Rayport's Medline citations

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Last modified on August 8, 2001