Postsynaptic diacylglycerol lipase α mediates retrograde endocannabinoid suppression of inhibition in mouse prefrontal cortex

摘要

Non-technical summaryIn multiple brain regions, endogenous cannabinoids suppress inhibitory synaptic transmission; however, the biochemical/molecular pathways for endocannabinoid synthesis are poorly understood. Endocannabinoid signalling may be crucial for microcircuit function in the prefrontal cortex (PFC), a cortical region involved in complex behaviours. However, endocannabinoid signalling remains largely unexplored in the PFC. Using enzymatic inhibitors, we show that modulation of inhibitory synaptic transmission in PFC neurons is mediated by the endocannabinoid 2-arachidonoylglycerol synthesized postsynaptically. Interestingly, diacylglycerol lipase (DAGL), the 2-arachidonoylglycerol synthesis enzyme, has two isoforms: DAGLα and DAGLβ. Studying PFC neurons from DAGLα^−/−, DAGLβ^−/− and wild-type mice, we show that only DAGLα is involved in the suppression of inhibitory transmission in the PFC.