TY - JOUR
T1 - Diacylglycerol Lipase Is Not Involved in Depolarization-Induced Suppression of Inhibition at Unitary Inhibitory Connections in Mouse Hippocampus
AU - Min, Rogier
AU - Testa-Silva, Guilherme
AU - Heistek, Tim S.
AU - Canto, Cathrin B.
AU - Lodder, Johannes C.
AU - Bisogno, Tiziana
AU - Di Marzo, Vincenzo
AU - Brussaard, Arjen B.
AU - Burnashev, Nail
AU - Mansvelder, Huibert D.
PY - 2010/2/17
Y1 - 2010/2/17
N2 - 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.
AB - 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.
U2 - 10.1523/JNEUROSCI.BC-3622-09.2010
DO - 10.1523/JNEUROSCI.BC-3622-09.2010
M3 - Article
C2 - 20164355
SN - 0270-6474
VL - 30
SP - 2710
EP - 2715
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 7
ER -