Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals

Lenkey, Nora and Kirizs, Tekla and Holderith, Noemi and Máté, Zoltán and Szabó, Gábor and Vizi, E. Sylvester and Hájos, Norbert and Nusser, Zoltan (2015) Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals. Nature communications, 6 (6557). pp. 1-14. ISSN 2041-1723

Preview

Text Lenkey Nat Comm 15.pdf Download (7MB) | Preview

Abstract

The release of GABA from cholecystokinin-containing interneurons is modulated by type-1 cannabinoid receptors (CB1). Here we tested the hypothesis that the strength of CB1-mediated modulation of GABA release is related to the CB1 content of axon terminals. Basket cell boutons have on average 78% higher CB1 content than those of dendritic-layer-innervating (DLI) cells, a consequence of larger bouton surface and higher CB1 density. The CB1 antagonist AM251 caused a 54% increase in action potential-evoked [Ca2+] in boutons of basket cells, but not in DLI cells. However, the effect of AM251 did not correlate with CB1 immunoreactivity of individual boutons. Moreover, a CB1 agonist decreased [Ca2+] in a cell type- and CB1-content-independent manner. Replica immunogold labelling demonstrated the colocalization of CB1 with the Cav2.2 Ca2+ channel subunit. Our data suggest that only a subpopulation of CB1s, within nanometre distances from their target Cav2.2 channels, are responsible for endocannabinoid-mediated modulation of GABA release.

Actions (login required)

Edit Item