Diacylglycerol lipase is not involved in depolarization-induced suppression of inhibition at unitary inhibitory connections in mouse hippocampus

Rogier Min, Guilherme Testa-Silva, Tim S Heistek, Cathrin B Canto, Johannes C Lodder, Tiziana Bisogno, Vincenzo Di Marzo, Arjen B Brussaard, Nail Burnashev, Huibert D Mansvelder

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2710-5
Number of pages6
JournalJournal of Neuroscience
Volume30
Issue number7
DOIs
Publication statusPublished - 17 Feb 2010

Cite this

Min, Rogier ; Testa-Silva, Guilherme ; Heistek, Tim S ; Canto, Cathrin B ; Lodder, Johannes C ; Bisogno, Tiziana ; Di Marzo, Vincenzo ; Brussaard, Arjen B ; Burnashev, Nail ; Mansvelder, Huibert D. / Diacylglycerol lipase is not involved in depolarization-induced suppression of inhibition at unitary inhibitory connections in mouse hippocampus. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 7. pp. 2710-5.
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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.",
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author = "Rogier Min and Guilherme Testa-Silva and Heistek, {Tim S} and Canto, {Cathrin B} and Lodder, {Johannes C} and Tiziana Bisogno and {Di Marzo}, Vincenzo and Brussaard, {Arjen B} and Nail Burnashev and Mansvelder, {Huibert D}",
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Diacylglycerol lipase is not involved in depolarization-induced suppression of inhibition at unitary inhibitory connections in mouse hippocampus. / Min, Rogier; Testa-Silva, Guilherme; Heistek, Tim S; Canto, Cathrin B; Lodder, Johannes C; Bisogno, Tiziana; Di Marzo, Vincenzo; Brussaard, Arjen B; Burnashev, Nail; Mansvelder, Huibert D.

In: Journal of Neuroscience, Vol. 30, No. 7, 17.02.2010, p. 2710-5.

Research output: Contribution to journalArticleAcademicpeer-review

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

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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.

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KW - Benzoxazines/pharmacology

KW - Cyclohexanones/pharmacology

KW - Electric Stimulation/methods

KW - Enzyme Inhibitors/pharmacology

KW - Excitatory Amino Acid Antagonists/pharmacology

KW - GABA Antagonists/pharmacology

KW - Green Fluorescent Proteins/genetics

KW - Hippocampus/cytology

KW - In Vitro Techniques

KW - Inhibitory Postsynaptic Potentials/drug effects

KW - Lipoprotein Lipase/antagonists & inhibitors

KW - Lysine/analogs & derivatives

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Morpholines/pharmacology

KW - Naphthalenes/pharmacology

KW - Neocortex/cytology

KW - Neural Inhibition/drug effects

KW - Neurons/drug effects

KW - Pyridazines/pharmacology

KW - Quinoxalines/pharmacology

KW - Receptor, Cannabinoid, CB1/agonists

KW - Valine/analogs & derivatives

U2 - 10.1523/JNEUROSCI.BC-3622-09.2010

DO - 10.1523/JNEUROSCI.BC-3622-09.2010

M3 - Article

VL - 30

SP - 2710

EP - 2715

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

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ER -