Cannabinoid sensitivity and synaptic properties of 2 GABAergic networks in the neocortex

Distinct networks of gamma-aminobutyric acidergic interneurons connected by electrical synapses can promote different patterns of activity in the neocortex. Cannabinoids affect memory and cognition by powerfully modulating a subset of inhibitory synapses; however, very little is known about the synaptic properties of the cannabinoid receptor-expressing neurons (CB(1)-positive irregular spiking [CB(1)-IS]) in the neocortex. Using paired recordings in neocortical slices, we 1st report here that synapses of CB(1)-IS cells, but not synapses of fast-spiking (FS) cells, are suppressed by release of endocannabinoids from pyramidal neurons. CB(1)-IS synapses were characterized by a very high failure rate that contrasted with the high reliability of FS synapses. Furthermore, CB(1)-IS cells received excitatory inputs less frequently compared with FS cells and made significantly less frequent inhibitory contacts onto local pyramids. These distinct synaptic properties together with their characteristic irregular firing suggest that CB(1)-IS cells play different role in neocortical function than that of FS cells. Thus, whereas the synaptic properties of FS cells can allow them to impose high-frequency rhythmic oscillatory activity, those of CB(1)-IS cells may lead to disruption of fast rhythmic oscillations. Our results suggest that activity-dependent release of cannabinoids, by blocking CB(1)-IS synapses, may alter the role of inhibition in neocortical circuits.