PT  - JOURNAL ARTICLE
AU  - Gergely G. Szabó
AU  - Nora Lenkey
AU  - Noemi Holderith
AU  - Tibor Andrási
AU  - Zoltan Nusser
AU  - Norbert Hájos
TI  - Presynaptic Calcium Channel Inhibition Underlies CB<sub>1</sub> Cannabinoid Receptor-Mediated Suppression of GABA Release
AID  - 10.1523/JNEUROSCI.0247-14.2014
DP  - 2014 Jun 04
TA  - The Journal of Neuroscience
PG  - 7958--7963
VI  - 34
IP  - 23
4099  - http://www.jneurosci.org/content/34/23/7958.short
4100  - http://www.jneurosci.org/content/34/23/7958.full
SO  - J. Neurosci.2014 Jun 04; 34
AB  - 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 [Ca2+] transients in mouse hippocampal slices. Our results reveal a power function with an exponent of 2.2 between the amplitude of uIPSCs and intrabouton [Ca2+]. Altering CB1 function by either increasing endocannabinoid production or removing its tonic activity allowed us to demonstrate that CB1 controls GABA release by inhibiting Ca2+ entry into presynaptic axon terminals via N-type (Cav2.2) Ca2+ channels. These results provide evidence for modulation of intrabouton Ca2+ influx into GABAergic axon terminals by CB1, leading to the effective suppression of synaptic inhibition.