Endocannabinoids limit metabotropic glutamate 5 receptor-mediated synaptic inhibition of striatal principal neurons.
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.
Centonze
Diego
D
Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy. centonze@uniroma2.it
Rossi
Silvia
S
Prosperetti
Chiara
C
Gasperi
Valeria
V
De Chiara
Valentina
V
Bari
Monica
M
Tscherter
Anne
A
Febbraro
Fabia
F
Bernardi
Giorgio
G
Maccarrone
Mauro
M
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
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