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The Journal of Neuroscience, November 14, 2007, 27(46):12464-12474; doi:10.1523/JNEUROSCI.0178-07.2007

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Cellular/Molecular
Somatodendritic Release of Glutamate Regulates Synaptic Inhibition in Cerebellar Purkinje Cells via Autocrine mGluR1 Activation

Ian C. Duguid, Yuriy Pankratov, Guy W. J. Moss, and Trevor G. Smart

Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom

Correspondence should be addressed to Prof. Trevor G. Smart, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: t.smart{at}ucl.ac.uk

In the cerebellum, the process of retrograde signaling via presynaptic receptors is important for the induction of short- and long-term changes in inhibitory synaptic transmission at interneuron–Purkinje cell (PC) synapses. Endocannabinoids, by activating presynaptic CB1 receptors, mediate a short-term decrease in inhibitory synaptic efficacy, whereas glutamate, acting on presynaptic NMDA receptors, induces a longer-latency sustained increase in GABA release. We now demonstrate that either low-frequency climbing fiber stimulation or direct somatic depolarization of Purkinje cells results in SNARE-dependent vesicular release of glutamate from the soma and dendrites of PCs. The activity-dependent release of glutamate caused the activation of postsynaptic metabotropic glutamate receptor 1 (mGluR1) on PC somatodendritic membranes, resulting in the cooperative release of endocannabinoids and an mGluR1-mediated slow membrane conductance. The activity of excitatory amino acid transporters regulated the spatial spread of glutamate and thus the extent of PC mGluR1 activation. We propose that activity-dependent somatodendritic glutamate release and autocrine activation of mGluR1 on PCs provides a powerful homeostatic mechanism to dynamically regulate inhibitory synaptic transmission in the cerebellar cortex.

Key words: metabotropic glutamate receptor; synaptic inhibition; GABA_A receptor; dendritic release; DSI; endocannabinoids

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Received July 13, 2006; revised Sept. 18, 2007; accepted Sept. 19, 2007.

Correspondence should be addressed to Prof. Trevor G. Smart, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: t.smart{at}ucl.ac.uk

This article has been cited by other articles:

				P. J. Sjostrom, E. A. Rancz, A. Roth, and M. Hausser Dendritic Excitability and Synaptic Plasticity Physiol Rev, April 1, 2008; 88(2): 769 - 840. [Abstract] [Full Text] [PDF]

				J. H. Shin, Y. S. Kim, and D. J. Linden Dendritic glutamate release produces autocrine activation of mGluR1 in cerebellar Purkinje cells PNAS, January 15, 2008; 105(2): 746 - 750. [Abstract] [Full Text] [PDF]

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