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 CB1controls 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.
Copyright © 2014 the authors 0270-6474/14/347958-06$15.00/0.

PMID:

 24899717
[PubMed – as supplied by publisher]