Electrical coupling among irregular-spiking GABAergic interneurons expressing cannabinoid receptors

Anatomical studies have shown that the G-protein-coupled cannabinoid receptor-1 (CB(1)) is selectively expressed in a subset of GABAergic interneurons. It has been proposed that these cells regulate rhythmic activity and play a key role mediating the cognitive actions of marijuana and endogenous cannabinoids. However, the physiology, anatomy, and synaptic connectivity of neocortical CB(1)-expressing interneurons remain poorly studied. We identified a population of CB(1)-expressing interneurons in layer II/III in mouse neocortical slices. These cells were multipolar or bitufted, had a widely extending axon, and exhibited a characteristic pattern of irregular spiking (IS) in response to current injection. CB(1)-expressing-IS (CB(1)-IS) cells were inhibitory, establishing GABA(A) receptor-mediated synapses onto pyramidal cells and other CB(1)-IS cells. Recently, electrical coupling among other classes of cortical interneurons has been shown to contribute to the generation of rhythmic synchronous activity in the neocortex. We therefore tested whether CB(1)-IS interneurons are interconnected via electrical synapses using paired recordings. We found that 90% (19 of 21 pairs) of simultaneously recorded pairs of CB(1)-IS cells were electrically coupled. The average coupling coefficient was similar to6%. Signaling through electrical synapses promoted coordinated firing among CB(1)-IS cells. Together, our results identify a population of electrically coupled CB(1)-IS GABAergic interneurons in the neocortex that share a unique morphology and a characteristic pattern of irregular spiking in response to current injection. The synaptic interactions of these cells may play an important role mediating the cognitive actions of cannabinoids and regulating coherent neocortical activity.