Impaired 2-AG signaling in hippocampal glutamatergic neurons : aggravation of anxiety-like behavior and unaltered seizure susceptibility

dc.contributor.authorGuggenhuber, Stephan
dc.contributor.authorRomo-Parra, Hector
dc.contributor.authorBindila, Laura
dc.contributor.authorLeschik, Julia
dc.contributor.authorLomazzo, Ermelinda
dc.contributor.authorRemmers, Floortje
dc.contributor.authorZimmermann, Tina
dc.contributor.authorLerner, Raissa
dc.contributor.authorKlugmann, Matthias
dc.contributor.authorPape, Hans-Christian
dc.contributor.authorLutz, Beat
dc.date.accessioned2022-06-20T08:24:54Z
dc.date.available2022-06-20T08:24:54Z
dc.date.issued2016
dc.description.abstractBackground: Postsynaptically generated 2-arachidonoylglycerol activates the presynaptic cannabinoid type-1 receptor, which is involved in synaptic plasticity at both glutamatergic and GABAergic synapses. However, the differential function of 2-arachidonoylglycerol signaling at glutamatergic vs GABAergic synapses in the context of animal behavior has not been investigated yet. Methods: Here, we analyzed the role of 2-arachidonoylglycerol signaling selectively in hippocampal glutamatergic neurons. Monoacylglycerol lipase, the primary degrading enzyme of 2-arachidonoylglycerol, is expressed at presynaptic sites of excitatory and inhibitory neurons. By adeno-associated virus-mediated overexpression of monoacylglycerol lipase in glutamatergic neurons of the mouse hippocampus, we selectively interfered with 2-arachidonoylglycerol signaling at glutamatergic synapses of these neurons. Results: Genetic modification of monoacylglycerol lipase resulted in a 50% decrease in 2-arachidonoylglycerol tissue levels without affecting the content of the second major endocannabinoid anandamide. A typical electrophysiological read-out for 2-arachidonoylglycerol signaling is the depolarization-induced suppression of excitation and of inhibition. Elevated monoacylglycerol lipase levels at glutamatergic terminals selectively impaired depolarization-induced suppression of excitation, while depolarization-induced suppression of inhibition was not significantly changed. At the behavioral level, mice with impaired hippocampal glutamatergic 2-arachidonoylglycerol signaling exhibited increased anxiety-like behavior but showed no alterations in aversive memory formation and seizure susceptibility. Conclusion: Our data indicate that 2-arachidonoylglycerol signaling selectively in hippocampal glutamatergic neurons is essential for the animal’s adaptation to aversive situations.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.identifier.doihttp://doi.org/10.25358/openscience-7173
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7187
dc.language.isoengde
dc.rightsCC-BY-NC-4.0*
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleImpaired 2-AG signaling in hippocampal glutamatergic neurons : aggravation of anxiety-like behavior and unaltered seizure susceptibilityen_GB
dc.typeZeitschriftenaufsatzde
jgu.journal.issue2de
jgu.journal.titleThe international journal of neuropsychopharmacologyde
jgu.journal.volume19de
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number2700
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.alternativepyv091de
jgu.publisher.doi10.1093/ijnp/pyv091de
jgu.publisher.issn1469-5111de
jgu.publisher.issn1461-1457de
jgu.publisher.nameOxford Univ. Pressde
jgu.publisher.placeOxfordde
jgu.publisher.urihttp://dx.doi.org/10.1093/ijnp/pyv091de
jgu.publisher.year2016
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode610de
jgu.type.dinitypeArticleen_GB
jgu.type.resourceTextde
jgu.type.versionPublished versionde
opus.affiliatedGuggenhuber, Stephan
opus.affiliatedBindila, Laura
opus.affiliatedLeschik, Julia
opus.affiliatedLomazzo, Ermelinda
opus.affiliatedRemmers, Floortje
opus.affiliatedZimmermann, Tina
opus.affiliatedLerner, Raissa
opus.affiliatedLutz, Beat
opus.date.modified2017-05-12T07:16:32Z
opus.identifier.opusid56552
opus.institute.number0404
opus.metadataonlyfalse
opus.organisation.stringFB 04: Medizin: Institut für Physiologische Chemie und Pathobiochemiede_DE
opus.subject.dfgcode00-000
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN

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