| First Author | Atwood BK | Year | 2012 |
| Journal | Neuropharmacology | Volume | 63 |
| Issue | 4 | Pages | 514-23 |
| PubMed ID | 22579668 | Mgi Jnum | J:196536 |
| Mgi Id | MGI:5488698 | Doi | 10.1016/j.neuropharm.2012.04.024 |
| Citation | Atwood BK, et al. (2012) CB(2) cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons. Neuropharmacology 63(4):514-23 |
| abstractText | The role of CB(2) in the central nervous system, particularly in neurons, has generated much controversy. Fueling the controversy are imperfect tools, which have made conclusive identification of CB(2) expressing neurons problematic. Imprecise localization of CB(2) has made it difficult to determine its function in neurons. Here we avoid the localization controversy and directly address the question if CB(2) can modulate neurotransmission. CB(2) was expressed in excitatory hippocampal autaptic neurons obtained from CB(1) null mice. Whole-cell patch clamp recordings were made from these neurons to determine the effects of CB(2) on short-term synaptic plasticity. CB(2) expression restored depolarization induced suppression of excitation to these neurons, which was lost following genetic ablation of CB(1). The endocannabinoid 2-arachidonylglycerol (2-AG) mimicked the effects of depolarization in CB(2) expressing neurons. Interestingly, ongoing basal production of 2-AG resulted in constitutive activation of CB(2), causing a tonic inhibition of neurotransmission that was relieved by the CB(2) antagonist AM630 or the diacylglycerol lipase inhibitor RHC80267. Through immunocytochemistry and analysis of spontaneous EPSCs, paired pulse ratios and coefficients of variation we determined that CB(2) exerts its function at a presynaptic site of action, likely through inhibition of voltage gated calcium channels. Therefore CB(2) expressed in neurons effectively mimics the actions of CB(1). Thus neuronal CB(2) is well suited to integrate into conventional neuronal endocannabinoid signaling processes, with its specific role determined by its unique and highly inducible expression profile. |
