Cannabinoid type 2 receptors mediate a cell type-specific self-inhibition in cortical neurons

Neuropharmacology
Alexander StumpfDietmar Schmitz

Abstract

Endogenous cannabinoids are diffusible lipid ligands of the main cannabinoid receptors type 1 and 2 (CB1R and CB2R). In the central nervous system endocannabinoids are produced in an activity-dependent manner and have been identified as retrograde modulators of synaptic transmission. Additionally, some neurons display a cell-autonomous slow self-inhibition (SSI) mediated by endocannabinoids. In these neurons, repetitive action potential firing triggers the production of endocannabinoids, which induce a long-lasting hyperpolarization of the membrane potential, rendering the cells less excitable. Different endocannabinoid receptors and effector mechanisms have been described underlying SSI in different cell types and brain areas. Here, we investigate SSI in neurons of layer 2/3 in the somatosensory cortex. High-frequency bursts of action potentials induced SSI in pyramidal cells (PC) and regular spiking non-pyramidal cells (RSNPC), but not in fast-spiking interneurons (FS). In RSNPCs the hyperpolarization was accompanied by a change in input resistance due to the activation of G protein-coupled inward-rectifying K+ (GIRK) channels. A CB2R-specific agonist induced the long-lasting hyperpolarization, whereas preincubation with a CB...Continue Reading

Citations

Sep 5, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Berhanu GeresuEphrem Engidawork
Jan 19, 2019·Brain Sciences·Balapal S Basavarajappa, Shivakumar Subbanna
Dec 4, 2020·Journal of Neuroscience Research·Moritoshi Hirono, Yuchio Yanagawa
Jan 16, 2021·Neuropharmacology·Lindsey ShapiroAndrew Escayg
Dec 30, 2020·International Journal of Molecular Sciences·Qing-Rong LiuEmmanuel S Onaivi
Dec 31, 2020·International Journal of Molecular Sciences·Joanna Agnieszka Komorowska-Müller, Anne-Caroline Schmöle
Nov 8, 2020·Neurochemistry International·Bao XueYing Wang
Jun 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rebecca FerrisiFrancesca Gado
Oct 31, 2021·Reviews in the Neurosciences·Robin VisvanatharMartina Blunder

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