Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release

CB1 cannabinoid receptors (CB1) are located at axon terminals and effectively control synaptic communication and thereby circuit operation widespread in the CNS. Although it is partially uncovered how CB1 activation leads to the reduction of synaptic excitation, the mechanisms of the decrease of GAB...

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Veröffentlicht in:The Journal of neuroscience 2014-06, Vol.34 (23), p.7958-7963
Hauptverfasser: Szabó, Gergely G, Lenkey, Nora, Holderith, Noemi, Andrási, Tibor, Nusser, Zoltan, Hájos, Norbert
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container_end_page 7963
container_issue 23
container_start_page 7958
container_title The Journal of neuroscience
container_volume 34
creator Szabó, Gergely G
Lenkey, Nora
Holderith, Noemi
Andrási, Tibor
Nusser, Zoltan
Hájos, Norbert
description CB1 cannabinoid receptors (CB1) are located at axon terminals and effectively control synaptic communication and thereby circuit operation widespread in the CNS. Although it is partially uncovered how CB1 activation leads to the reduction of synaptic excitation, the mechanisms of the decrease of GABA release upon activation of these cannabinoid receptors remain elusive. To determine the mechanisms underlying the suppression of synaptic transmission by CB1 at GABAergic synapses, we recorded unitary IPSCs (uIPSCs) at cholecystokinin-expressing interneuron-pyramidal cell connections and imaged presynaptic [Ca(2+)] transients in mouse hippocampal slices. Our results reveal a power function with an exponent of 2.2 between the amplitude of uIPSCs and intrabouton [Ca(2+)]. Altering CB1 function by either increasing endocannabinoid production or removing its tonic activity allowed us to demonstrate that CB1 controls GABA release by inhibiting Ca(2+) entry into presynaptic axon terminals via N-type (Cav2.2) Ca(2+) channels. These results provide evidence for modulation of intrabouton Ca(2+) influx into GABAergic axon terminals by CB1, leading to the effective suppression of synaptic inhibition.
doi_str_mv 10.1523/JNEUROSCI.0247-14.2014
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Animals
Animals, Newborn
Brief Communications
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Cholecystokinin - genetics
Cholecystokinin - pharmacology
Female
gamma-Aminobutyric Acid - metabolism
Hippocampus - cytology
In Vitro Techniques
Inhibitory Postsynaptic Potentials - drug effects
Inhibitory Postsynaptic Potentials - physiology
Interneurons - drug effects
Interneurons - physiology
Luminescent Proteins - genetics
Male
Mice
Mice, Transgenic
omega-Conotoxin GVIA - pharmacology
Piperidines - pharmacology
Presynaptic Terminals - drug effects
Presynaptic Terminals - metabolism
Pyrazoles - pharmacology
Receptor, Cannabinoid, CB1 - metabolism
Synapses - drug effects
Synapses - physiology
title Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release
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