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Autoren: Guggenhuber, Stephan
Romo-Parra, Hector
Bindila, Laura
Leschik, Julia
Lomazzo, Ermelinda
Remmers, Floortje
Zimmermann, Tina
Lerner, Raissa
Klugmann, Matthias
Pape, Hans-Christian
Lutz, Beat
Titel: Impaired 2-AG signaling in hippocampal glutamatergic neurons : aggravation of anxiety-like behavior and unaltered seizure susceptibility
Online-Publikationsdatum: 20-Jun-2022
Sprache des Dokuments: Englisch
Zusammenfassung/Abstract: Background: 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.
DDC-Sachgruppe: 610 Medizin
610 Medical sciences
Veröffentlichende Institution: Johannes Gutenberg-Universität Mainz
Organisationseinheit: FB 04 Medizin
Veröffentlichungsort: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-7173
Version: Published version
Publikationstyp: Zeitschriftenaufsatz
Nutzungsrechte: CC BY-NC
Informationen zu den Nutzungsrechten: https://creativecommons.org/licenses/by-nc/4.0/
Zeitschrift: The international journal of neuropsychopharmacology
19
2
Seitenzahl oder Artikelnummer: pyv091
Verlag: Oxford Univ. Press
Verlagsort: Oxford
Erscheinungsdatum: 2016
ISSN: 1469-5111
1461-1457
URL der Originalveröffentlichung: http://dx.doi.org/10.1093/ijnp/pyv091
DOI der Originalveröffentlichung: 10.1093/ijnp/pyv091
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