Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors

T Maejima; K Hashimoto; T Yoshida; A Aiba; M Kano

doi:10.1016/s0896-6273(01)00375-0

Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors

Neuron. 2001 Aug 16;31(3):463-75. doi: 10.1016/s0896-6273(01)00375-0.

Authors

T Maejima¹, K Hashimoto, T Yoshida, A Aiba, M Kano

Affiliation

¹ Department of Physiology, Kanazawa University School of Medicine, Takara-machi, Kanazawa 920-8640, Japan.

PMID: 11516402
DOI: 10.1016/s0896-6273(01)00375-0

Abstract

We report a type of synaptic modulation that involves retrograde signaling from postsynaptic metabotropic glutamate receptors (mGluRs) to presynaptic cannabinoid receptors. Activation of mGluR subtype 1 (mGluR1) expressed in cerebellar Purkinje cells (PCs) reduced neurotransmitter release from excitatory climbing fibers. This required activation of G proteins but not Ca2+ elevation in postsynaptic PCs. This effect was occluded by a cannabinoid agonist and totally abolished by cannabinoid antagonists. Depolarization-induced Ca2+ transients in PCs also caused cannabinoid receptor-mediated presynaptic inhibition. Thus, endocannabinoid production in PCs can be initiated by two distinct stimuli. Activation of mGluR1 by repetitive stimulation of parallel fibers, the other excitatory input to PCs, caused transient cannabinoid receptor-mediated depression of climbing fiber input. Our data highlight a signaling mechanism whereby activation of postsynaptic mGluR retrogradely influences presynaptic functions via endocannabinoid system.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism
Cannabinoid Receptor Modulators
Cannabinoids / metabolism*
Cerebellum / physiology*
Evoked Potentials / drug effects
Evoked Potentials / physiology*
In Vitro Techniques
Methoxyhydroxyphenylglycol / analogs & derivatives*
Methoxyhydroxyphenylglycol / pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Presynaptic Terminals / drug effects
Presynaptic Terminals / physiology*
Promoter Regions, Genetic
Purkinje Cells / drug effects
Purkinje Cells / physiology*
Rats
Receptors, Cannabinoid
Receptors, Drug / drug effects
Receptors, Drug / physiology*
Receptors, Metabotropic Glutamate / deficiency
Receptors, Metabotropic Glutamate / genetics
Receptors, Metabotropic Glutamate / physiology*
Signal Transduction / drug effects
Signal Transduction / physiology

Substances

Cannabinoid Receptor Modulators
Cannabinoids
Receptors, Cannabinoid
Receptors, Drug
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1
Methoxyhydroxyphenylglycol
Calcium
3,4-dihydroxyphenylglycol