Premium
Postsynaptic diacylglycerol lipase α mediates retrograde endocannabinoid suppression of inhibition in mouse prefrontal cortex
Author(s) -
Yoshino Hiroki,
Miyamae Takeaki,
Hansen Gwenn,
Zambrowicz Brian,
Flynn Michael,
Pedicord Donna,
Blat Yuval,
Westphal Ryan S.,
Zaczek Robert,
Lewis David A.,
GonzalezBurgos Guillermo
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.212225
Subject(s) - diacylglycerol lipase , endocannabinoid system , anandamide , 2 arachidonoylglycerol , chemistry , cannabinoid receptor , depolarization induced suppression of inhibition , medicine , endocrinology , monoacylglycerol lipase , diacylglycerol kinase , agonist , biochemistry , receptor , biology , protein kinase c , signal transduction
Non‐Technical Summary In 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.