title: Functional CB1 receptors are broadly expressed in neocortical GABAergic and glutamatergic neurons.
abstract: The cannabinoid receptor CB1 is found in abundance in brain neurons, whereas CB2 is essentially expressed outside the brain. In the neocortex, CB1 is observed predominantly on large cholecystokinin (CCK)-expressing interneurons. However, physiological evidence suggests that functional CB1 are present on other neocortical neuronal types. We investigated the expression of CB1 and CB2 in identified neurons of rat neocortical slices using single-cell RT-PCR. We found that 63% of somatostatin (SST)-expressing and 69% of vasoactive intestinal polypeptide (VIP)-expressing interneurons co-expressed CB1. As much as 49% of pyramidal neurons expressed CB1. In contrast, CB2 was observed in a small proportion of neocortical neurons. We performed whole cell recordings of pyramidal neurons to corroborate our molecular findings. Inhibitory postsynaptic currents (IPSCs) induced by a mixed muscarinic/nicotinic cholinergic agonist showed depolarization-induced suppression of inhibition and were decreased by the CB1 agonist WIN-55212-2 (WIN-2), suggesting that interneurons excited by cholinergic agonists (mainly SST and VIP neurons) possess CB1. IPSCs elicited by a nicotinic receptor agonist were also reduced in the presence of WIN-2, suggesting that neurons excited by nicotinic agonists (mainly VIP neurons) indeed possess CB1. WIN-2 largely decreased excitatory postsynaptic currents evoked by intracortical electrical stimulation, pointing at the presence of CB1 on glutamatergic pyramidal neurons. All WIN-2 effects were strongly reduced by the CB1 antagonist AM 251. We conclude that CB1 is expressed in various neocortical neuronal populations, including glutamatergic neurons. Our combined molecular and physiological data suggest that CB1 widely mediates endocannabinoid effects on glutamatergic and GABAergic transmission to modulate cortical networks.
authors.affiliation: Laboratoire de Neurobiologie et Diversité Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7637, Ecole Supérieure de Physique et de Chimie Industrielles, Paris, France.
authors.forename: Elisa L
authors.initials: EL
authors.lastname: Hill
authors.forename: Thierry
authors.initials: T
authors.lastname: Gallopin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Férézou
authors.forename: Bruno
authors.initials: B
authors.lastname: Cauli
authors.forename: Jean
authors.initials: J
authors.lastname: Rossier
authors.forename: Paul
authors.initials: P
authors.lastname: Schweitzer
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lambolez
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D009415:Nerve Net / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis*; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D002186:Cannabinoids; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid