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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, including pyramidal glutamatergic neurons. 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) 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. IPSCs induced by a mixed muscarinic/nicotinic cholinergic agonist showed depolarization-induced suppression of inhibition and were decreased by the CB1 agonist 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 EPSCs 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.
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Submitted on : Thursday, November 26, 2020 - 6:25:01 PM
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Elisa L. Hill, Thierry Gallopin, Isabelle Ferezou, Bruno Cauli, Jean Rossier, et al.. Functional CB1 receptors are broadly expressed in neocortical GABAergic and glutamatergic neurons.. Journal of Neurophysiology, American Physiological Society, 2007, 97, pp.000. ⟨10.1152/jn.00603.2006⟩. ⟨hal-00134867⟩



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