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The Journal of Neuroscience, November 19, 2003, 23(33):10585-10592

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Cellular/Molecular
Glutamate Spillover in the Striatum Depresses Dopaminergic Transmission by Activating Group I Metabotropic Glutamate Receptors

Hui Zhang¹ and David Sulzer^1,2,3

Departments of ¹Neurology and ²Psychiatry, Columbia University, New York, New York 10032, and ³Department of Neuroscience, New York State Psychiatric Institute, New York, New York 10032

Cortical glutamate and substantia nigra dopamine (DA) afferents converge onto the dendritic spines of medium spiny neurons (MSNs) in the striatum where they act to modulate motor and cognitive functions. The released DA spills over from its synapse and is thought to regulate glutamatergic input by acting on distal DA receptors located on corticostriatal axon terminals. By monitoring evoked DA release directly using fast-scan cyclic voltammetry, we report a reciprocal modulation by glutamate spillover on evoked striatal DA release, induced by either glutamate uptake blockade or high-frequency stimulation of corticostriatal tracts. We demonstrate that this modulation is attributable to the activation of group I metabotropic glutamate receptors. Thus, under conditions in which glutamate escapes the confines of its synapse, it can elicit the presynaptic suppression of dopaminergic neurotransmission.

Key words: corticostriatal; glutamate spillover; EAATs blockers; dopamine; cyclic voltammetry; mGluRs; striatal slice

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Received June 25, 2003; revised September 9, 2003; accepted September 22, 2003.

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