title: Diacylglycerol lipase is not involved in depolarization-induced suppression of inhibition at unitary inhibitory connections in mouse hippocampus.
abstract: Endocannabinoids control hippocampal inhibitory synaptic transmission through activation of presynaptic CB(1) receptors. During depolarization-induced suppression of inhibition (DSI), endocannabinoids are synthesized upon postsynaptic depolarization. The endocannabinoid 2-arachidonoylglycerol (2-AG) may mediate hippocampal DSI. Currently, the best studied pathway for biosynthesis of 2-AG involves the enzyme diacylglycerol lipase (DAGL). However, whether DAGL is necessary for hippocampal DSI is controversial and was not systematically addressed. Here, we investigate DSI at unitary connections between CB(1) receptor-containing interneurons and pyramidal neurons in CA1. We found that the novel DAGL inhibitor OMDM-188, as well as the established inhibitor RHC-80267, did not affect DSI. As reported previously, effects of the DAGL inhibitor tetrahydrolipstatin depended on the application method: postsynaptic intracellular application left DSI intact, while incubation blocked DSI. We show that all DAGL inhibitors tested block slow self-inhibition in neocortical interneurons, which involves DAGL. We conclude that DAGL is not involved in DSI at unitary connections in hippocampus.
authors.affiliation: Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Min
authors.forename: Guilherme
authors.initials: G
authors.lastname: Testa-Silva
authors.forename: Tim S
authors.initials: TS
authors.lastname: Heistek
authors.forename: Cathrin B
authors.initials: CB
authors.lastname: Canto
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Lodder
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Arjen B
authors.initials: AB
authors.lastname: Brussaard
authors.forename: Nail
authors.initials: N
authors.lastname: Burnashev
authors.forename: Huibert D
authors.initials: HD
authors.lastname: Mansvelder
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000172:deficiency; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D048588:Benzoxazines; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009025:Morpholines; D009281:Naphthalenes; D011724:Pyridazines; D011810:Quinoxalines; D043884:Receptor, Cannabinoid, CB1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; C049853:gabazine; D008071:Lipoprotein Lipase; C013411:biocytin; D014633:Valine; D008239:Lysine