Journal article
Control of inhibition by the direct action of cannabinoids on GABAA receptors
Cerebral Cortex, Vol.25(9), pp.2440-2455
2015
Abstract
Cannabinoids are known to regulate inhibitory synaptic transmission via activation of presynaptic G protein-coupled cannabinoid CB1 receptors (CB1Rs). Additionally, recent studies suggest that cannabinoids can also directly interact with recombinant GABAA receptors (GABAARs), potentiating currents activated by micromolar concentrations of γ-aminobutyric acid (GABA). However, the impact of this direct interaction on GABAergic inhibition in central nervous system is unknown. Here we report that currents mediated by recombinant GABAARs activated by high (synaptic) concentrations of GABA as well as GABAergic inhibitory postsynaptic currents (IPSCs) at neocortical fast spiking (FS) interneuron to pyramidal neuron synapses are suppressed by exogenous and endogenous cannabinoids in a CB1R-independent manner. This IPSC suppression may account for disruption of inhibitory control of pyramidal neurons by FS interneurons. At FS interneuron to pyramidal neuron synapses, endocannabinoids induce synaptic low-pass filtering of GABAAR-mediated currents evoked by high-frequency stimulation. The CB1R-independent suppression of inhibition is synapse specific. It does not occur in CB1R containing hippocampal cholecystokinin-positive interneuron to pyramidal neuron synapses. Furthermore, in contrast to synaptic receptors, the activity of extrasynaptic GABAARs in neocortical pyramidal neurons is enhanced by cannabinoids in a CB1R-independent manner. Thus, cannabinoids directly interact differentially with synaptic and extrasynaptic GABAARs, providing a potent novel context-dependent mechanism for regulation of inhibition. © The Author 2014. Published by Oxford University Press. All rights reserved.
Details
- Title
- Control of inhibition by the direct action of cannabinoids on GABAA receptors
- Authors
- T Golovko (Author) - University of Heidelberg, GermanyR Min (Author) - VU University, NetherlandsN Lozovaya (Author) - Aix-Marseille Université, FranceC Falconer (Author) - Dundee University, United KingdomN Yatsenko (Author) - Bogomoletz Institute of Physiology, UkraineT Tsintsadze (Author) - Aix-Marseille Université, FranceV Tsintsadze (Author) - Aix-Marseille Université, FranceC Ledent (Author) - Université Libre de Bruxelles, BelgiumRobert J Harvey (Author) - University College London, United KingdomD Belelli (Author) - Dundee University, United KingdomJ J Lambert (Author) - Dundee University, United KingdomA Rozov (Author) - University of Heidelberg, GermanyN Burnashev (Author) - VU University, Netherlands
- Publication details
- Cerebral Cortex, Vol.25(9), pp.2440-2455
- Publisher
- Oxford University Press
- Date published
- 2015
- DOI
- 10.1093/cercor/bhu045
- ISSN
- 1047-3211
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99450416602621
- Output Type
- Journal article
Metrics
216 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Web Of Science research areas
- Neurosciences
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites