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The Journal of Neuroscience, June 1, 2002, 22(11):4346-4356

Role of P/Q-Ca²⁺ Channels in Metabotropic Glutamate Receptor 2/3-Dependent Presynaptic Long-Term Depression at Nucleus Accumbens Synapses

David Robbe¹, Gérard Alonso², Séverine Chaumont³, Joël Bockaert¹, and Olivier J. Manzoni¹

Centre National de la Recherche Scientifique ¹ Unité Propre de Recherche 9023, ² Unité Mixte de Recherche 5101, and ³ Unité Propre de Recherche 1142, 34094 Montpellier Cedex 05, France

The nucleus accumbens (NAc) is an important cerebral area involved in reward and spatial memory (Pennartz et al., 1994), but little is known about synaptic plasticity in this region. Here, electron microscopy revealed that, in the NAc, metabotropic glutamate receptors 2/3 (mGlu2/3) immunostaining was essentially associated with axonal terminals and glial processes, whereas postsynaptic dendrites and neuronal cell bodies were unstained. Electrophysiological techniques in the NAc slice preparation demonstrated that activation of mGlu2/3 with synaptically released glutamate or specific exogenous agonist, such as LY354740 (200 nM, 10 min), induced long-term depression of excitatory synaptic transmission (mGlu2/3-LTD). Tetanic-LTD and pharmacological mGlu2/3-LTD occluded each other, suggesting common mechanisms. The mGlu2/3-LTD did not require synaptic activity but depended on the cAMP-protein kinase A cascade. Selective inhibition of P/Q-type Ca²⁺ channels with -agatoxin-IVA occluded the expression of mGlu2/3-LTD, and, conversely, the inhibitory effects of -agatoxin-IVA were abolished during mGlu2/3-LTD. Thus, mGlu2/3 play an important role in the control of use-dependent synaptic plasticity at prelimbic cortex-NAc synapses: their activation causes a form of LTD mediated by the long-lasting reduction of P/Q-type Ca²⁺channels contribution to transmitter release.

Key words: nucleus accumbens; long-term depression; metabotropic glutamate receptors; mGlu2/3; presynaptic inhibition; mice; prelimbic cortex; calcium channels

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22114346-11$05.00/0

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