Electrical Coupling among Irregular-Spiking GABAergic Interneurons Expressing Cannabinoid Receptors

Abstract

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 ϳ6%. 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.

Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor

“…CCK ϩ interneurons exhibit a predominant regular-spiking phenotype in vivo (5,22). Whole-cell recordings of cultured CB 1 R ϩ cells revealed irregular or regular discharge patterns (Fig.…”

“…To determine whether eCBs affect interneuron migration and differentiation, we generated subset-specific interneuron cultures from E19͞20 rat cortices by immunomagnetic sorting for the CB 1 R (13, 16). Isolated neurons (72,000 Ϯ 16,000 cells per embryo) exhibited bipolar or multipolar somatodendritic morphologies (22) and were immunoreactive for the GABA-synthesizing enzyme GAD (Ͼ96%), vesicular GABA transporter, ␤-III-tubulin, fatty-acid amide hydrolase, and CB 1 Rs (Fig. 1 B-FЈ; see also Supporting Materials and Methods and Table 1, which are published as supporting information on the PNAS web site).…”

Gap Junctions and Emergent Rhythms

“…Another form of gap junction modulation can be traced to cannabinoids. Gap junction coupling can be found among irregular spiking GABAergic interneurons that express cannabinoid receptors [23]. Interestingly, the potentiation of such coupling by cannabinoids has recently been reported [10].…”

Properties of external plexiform layer interneurons in mouse olfactory bulb slices

“…The transgenic mice expressed enhanced green fluorescent protein (GFP) under control of the regulatory region of the 65 kDa mouse glutamic acid decarboxylase (GAD) 65 gene (Erdélyi et al, 2002;Galarreta et al, 2004). Horizontal slices (400 m thick) were obtained using a vibratome (Series 1000, Ted Pella Inc., Redding, CA, USA) as previously described (Heyward et al, 2001).…”