Endocannabinoids limit metabotropic glutamate 5 receptor-mediated synaptic inhibition of striatal principal neurons

Diego Centonze; Silvia Rossi; Chiara Prosperetti; Valeria Gasperi; Valentina De Chiara; Monica Bari; Anne Tscherter; Fabia Febbraro; Giorgio Bernardi; Mauro Maccarrone

doi:10.1016/j.mcn.2007.03.005

Endocannabinoids limit metabotropic glutamate 5 receptor-mediated synaptic inhibition of striatal principal neurons

Mol Cell Neurosci. 2007 Jun;35(2):302-10. doi: 10.1016/j.mcn.2007.03.005. Epub 2007 Mar 15.

Authors

Diego Centonze¹, Silvia Rossi, Chiara Prosperetti, Valeria Gasperi, Valentina De Chiara, Monica Bari, Anne Tscherter, Fabia Febbraro, Giorgio Bernardi, Mauro Maccarrone

Affiliation

¹ Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy. [email protected]

PMID: 17434747
DOI: 10.1016/j.mcn.2007.03.005

Abstract

Synaptic transmission in the striatum is regulated by metabotropic glutamate (mGlu) receptors through pre- and postsynaptic mechanisms. We investigated the involvement of mGlu 1 and 5 receptors in the control of both excitatory and inhibitory transmission in the striatum. The mGlu 1 and 5 receptor agonist 3,5-DHPG failed to affect glutamate transmission, while it caused a biphasic effect on GABA transmission, characterized by early increase and late decrease in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from striatal principal neurons. Both mGlu 1 and 5 receptors were involved in the early response to 3,5-DHPG, through membrane depolarization of striatal GABAergic interneurons and action potential generation. The 3,5-DHPG-mediated late depression of inhibitory inputs to striatal principal neurons was conversely secondary to mGlu 5 receptor activation and subsequent endocannabinoid release. In conclusion, we have identified an mGlu-dependent mechanism of GABA transmission regulation of potential relevance for physiological neuronal activity.

Publication types

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

MeSH terms

Action Potentials / drug effects
Action Potentials / physiology
Animals
Cannabinoid Receptor Modulators / antagonists & inhibitors
Cannabinoid Receptor Modulators / pharmacology*
Chromones / pharmacology
Corpus Striatum / cytology*
Drug Interactions
Endocannabinoids*
Excitatory Amino Acid Agonists / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
In Vitro Techniques
Interneurons / drug effects
Interneurons / physiology*
Methoxyhydroxyphenylglycol / analogs & derivatives
Methoxyhydroxyphenylglycol / pharmacology
Mice
Mice, Inbred C57BL
Neural Inhibition / drug effects
Neural Inhibition / physiology*
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / physiology*
Synaptic Transmission / drug effects*
Synaptic Transmission / physiology
Tetrodotoxin / pharmacology
Time Factors
gamma-Aminobutyric Acid / metabolism

Substances

7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester
Cannabinoid Receptor Modulators
Chromones
Endocannabinoids
Excitatory Amino Acid Agonists
Excitatory Amino Acid Antagonists
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
Tetrodotoxin
Methoxyhydroxyphenylglycol
gamma-Aminobutyric Acid
3,4-dihydroxyphenylglycol