CB2 cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons

NEUROPHARMACOLOGY

卷:63

Article

Atwood, Brady K.¹  Straiker, Alex¹  Mackie, Ken¹ 

[1] Indiana Univ, Dept Psychol & Brain Sci, Gill Ctr Biomol Sci, Bloomington, IN 47405 USA

关键词: CB2;    Cannabinoid receptor;    Autaptic neurons;    DSE;    Endocannabinoid;   

DOI  :  10.1016/j.neuropharm.2012.04.024

来源: Elsevier

【 摘 要 】

The role of CB2 in the central nervous system, particularly in neurons, has generated much controversy. Fueling the controversy are imperfect tools, which have made conclusive identification of CB2 expressing neurons problematic. Imprecise localization of CB2 has made it difficult to determine its function in neurons. Here we avoid the localization controversy and directly address the question if CB2 can modulate neurotransmission. CB2 was expressed in excitatory hippocampal autaptic neurons obtained from CB1 null mice. Whole-cell patch clamp recordings were made from these neurons to determine the effects of CB2 on short-term synaptic plasticity. CB2 expression restored depolarization induced suppression of excitation to these neurons, which was lost following genetic ablation of CBI. The endocannabinoid 2-arachidonylglycerol (2-AG) mimicked the effects of depolarization in CB2 expressing neurons. Interestingly, ongoing basal production of 2-AG resulted in constitutive activation of CB2, causing a tonic inhibition of neurotransmission that was relieved by the CB2 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 CB2 exerts its function at a presynaptic site of action, likely through inhibition of voltage gated calcium channels. Therefore CB2 expressed in neurons effectively mimics the actions of CB1. Thus neuronal CB2 is well suited to integrate into conventional neuronal endocannabinoid signaling processes, with its specific role determined by its unique and highly inducible expression profile. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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