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Nat Neurosci. 2004 May;7(5):525-33. Epub 2004 Apr 18.

Retrograde activation of presynaptic NMDA receptors enhances GABA release at cerebellar interneuron-Purkinje cell synapses.

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Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.


Synaptic inhibition is a vital component in the control of cell excitability within the brain. Here we report a newly identified form of inhibitory synaptic plasticity, termed depolarization-induced potentiation of inhibition, in rodents. This mechanism strongly potentiated synaptic transmission from interneurons to Purkinje cells after the termination of depolarization-induced suppression of inhibition. It was triggered by an elevation of Ca(2+) in Purkinje cells and the subsequent retrograde activation of presynaptic NMDA receptors. These glutamate receptors promoted the spontaneous release of Ca(2+) from presynaptic ryanodine-sensitive Ca(2+) stores. Thus, NMDA receptor-mediated facilitation of transmission at this synapse provides a regulatory mechanism that can dynamically alter the synaptic efficacy at inhibitory synapses.

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