PMID- 24646614
OWN - NLM
STAT- MEDLINE
DCOM- 20160505
LR  - 20220129
IS  - 1460-2199 (Electronic)
IS  - 1047-3211 (Linking)
VI  - 25
IP  - 9
DP  - 2015 Sep
TI  - Control of Inhibition by the Direct Action of Cannabinoids on GABAA Receptors.
PG  - 2440-55
LID - 10.1093/cercor/bhu045 [doi]
AB  - 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 gamma-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.
CI  - (c) The Author 2014. Published by Oxford University Press. All rights reserved. For 
      Permissions, please e-mail: journals.permissions@oup.com.
FAU - Golovko, Tatiana
AU  - Golovko T
AD  - Department of Clinical Neurobiology, University Hospital for Neurology, 
      University of Heidelberg, 69120 Heidelberg, Germany Current Address: Research 
      Group Computational Neuroscience, Central Institute of Mental Health, 68159 
      Mannheim, Germany.
FAU - Min, Rogier
AU  - Min R
AD  - Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive 
      Research, VU University, 1081 HV Amsterdam, The Netherlands Current Address: 
      Molecular Visual Plasticity Group, Netherlands Institute for Neuroscience, 1105 
      BA Amsterdam, The Netherlands.
FAU - Lozovaya, Natalia
AU  - Lozovaya N
AD  - Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01204 
      Kiev, Ukraine INSERM U901, Institut de Neurobiologie de la Mediterranee (INMED), 
      13273 Marseille, France UMR901, Aix-Marseille Universite, 13273 Marseille, 
      France.
FAU - Falconer, Caroline
AU  - Falconer C
AD  - Division of Neuroscience, Medical Research Institute, Ninewells Hospital and 
      Medical School, Dundee University, Dundee DD1 9SY, UK.
FAU - Yatsenko, Natalia
AU  - Yatsenko N
AD  - Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01204 
      Kiev, Ukraine.
FAU - Tsintsadze, Timur
AU  - Tsintsadze T
AD  - INSERM U901, Institut de Neurobiologie de la Mediterranee (INMED), 13273 
      Marseille, France UMR901, Aix-Marseille Universite, 13273 Marseille, France.
FAU - Tsintsadze, Vera
AU  - Tsintsadze V
AD  - INSERM U901, Institut de Neurobiologie de la Mediterranee (INMED), 13273 
      Marseille, France UMR901, Aix-Marseille Universite, 13273 Marseille, France.
FAU - Ledent, Catherine
AU  - Ledent C
AD  - Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire 
      (IRIBHM), Universite Libre de Bruxelles, 1050 Bruxelles, Belgium.
FAU - Harvey, Robert J
AU  - Harvey RJ
AD  - Department of Pharmacology, UCL School of Pharmacy, London WC1N 1AX, UK.
FAU - Belelli, Delia
AU  - Belelli D
AD  - Division of Neuroscience, Medical Research Institute, Ninewells Hospital and 
      Medical School, Dundee University, Dundee DD1 9SY, UK.
FAU - Lambert, Jeremy J
AU  - Lambert JJ
AD  - Division of Neuroscience, Medical Research Institute, Ninewells Hospital and 
      Medical School, Dundee University, Dundee DD1 9SY, UK.
FAU - Rozov, Andrei
AU  - Rozov A
AD  - Department of Clinical Neurobiology, University Hospital for Neurology, 
      University of Heidelberg, 69120 Heidelberg, Germany Division of Neuroscience, 
      Medical Research Institute, Ninewells Hospital and Medical School, Dundee 
      University, Dundee DD1 9SY, UK Laboratory of Neurobiology, Kazan Federal 
      University, Kazan, Russia.
FAU - Burnashev, Nail
AU  - Burnashev N
AD  - Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive 
      Research, VU University, 1081 HV Amsterdam, The Netherlands INSERM U901, Institut 
      de Neurobiologie de la Mediterranee (INMED), 13273 Marseille, France UMR901, 
      Aix-Marseille Universite, 13273 Marseille, France.
LA  - eng
GR  - MR/J004049/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20140318
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Cannabinoids)
RN  - 0 (GABA Agents)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptors, GABA)
SB  - IM
MH  - Action Potentials/drug effects/genetics
MH  - Animals
MH  - Animals, Newborn
MH  - Cannabinoids/*metabolism/pharmacology
MH  - GABA Agents/pharmacology
MH  - Hippocampus/cytology
MH  - Humans
MH  - In Vitro Techniques
MH  - Inhibitory Postsynaptic Potentials/drug effects/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neural Inhibition/drug effects/*physiology
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Receptor, Cannabinoid, CB1/genetics/metabolism
MH  - Receptors, GABA/*metabolism
MH  - Synaptic Transmission/drug effects/genetics
MH  - Transfection
OTO - NOTNLM
OT  - CB1 receptors
OT  - DSI
OT  - endocannabinoids
OT  - fast-spiking interneurons
OT  - inhibitory synaptic transmission
OT  - neocortex
EDAT- 2014/03/22 06:00
MHDA- 2016/05/06 06:00
CRDT- 2014/03/21 06:00
PHST- 2014/03/21 06:00 [entrez]
PHST- 2014/03/22 06:00 [pubmed]
PHST- 2016/05/06 06:00 [medline]
AID - bhu045 [pii]
AID - 10.1093/cercor/bhu045 [doi]
PST - ppublish
SO  - Cereb Cortex. 2015 Sep;25(9):2440-55. doi: 10.1093/cercor/bhu045. Epub 2014 Mar 
      18.