title: Endocannabinoids limit metabotropic glutamate 5 receptor-mediated synaptic inhibition of striatal principal neurons.
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.
authors: Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy. centonze@uniroma2.it
authors: Diego
authors: D
authors: Centonze
authors: Silvia
authors: S
authors: Rossi
authors: Chiara
authors: C
authors: Prosperetti
authors: Valeria
authors: V
authors: Gasperi
authors: Valentina
authors: V
authors: De Chiara
authors: Monica
authors: M
authors: Bari
authors: Anne
authors: A
authors: Tscherter
authors: Fabia
authors: F
authors: Febbraro
authors: Giorgio
authors: G
authors: Bernardi
authors: Mauro
authors: M
authors: Maccarrone
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology*; D004347:Drug Interactions; D063388:Endocannabinoids; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D063385:Cannabinoid Receptor Modulators; D002867:Chromones; D063388:Endocannabinoids; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013779:Tetrodotoxin; D008734:Methoxyhydroxyphenylglycol; D005680:gamma-Aminobutyric Acid; C010117:3,4-dihydroxyphenylglycol