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Somatodendritic release of glutamate regulates synaptic inhibition in cerebellar Purkinje cells via autocrine mGluR1 activation

Duguid, IC; Pankratov, Y; Moss, GWJ; Smart, TG; (2007) Somatodendritic release of glutamate regulates synaptic inhibition in cerebellar Purkinje cells via autocrine mGluR1 activation. J NEUROSCI , 27 (46) 12464 - 12474. 10.1523/JNEUROSCI.0178-07.2007.

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Abstract

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 PCsomatodendritic 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.

Type: Article
Title: Somatodendritic release of glutamate regulates synaptic inhibition in cerebellar Purkinje cells via autocrine mGluR1 activation
DOI: 10.1523/JNEUROSCI.0178-07.2007
Keywords: metabotropic glutamate receptor, synaptic inhibition, GABA(A) receptor, dendritic release, DSI, endocannabinoids, DEPOLARIZED POSTSYNAPTIC NEURONS, PRESYNAPTIC NMDA RECEPTORS, LONG-TERM DEPRESSION, ENDOGENOUS CANNABINOIDS, CLIMBING FIBER, ENDOCANNABINOID RELEASE, RETROGRADE INHIBITION, CALCIUM TRANSIENTS, PYRAMIDAL CELLS, SYNAPSES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: http://discovery.ucl.ac.uk/id/eprint/177024
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