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Authors: Guggenhuber, Stephan
Romo-Parra, Hector
Bindila, Laura
Leschik, Julia
Lomazzo, Ermelinda
Remmers, Floortje
Zimmermann, Tina
Lerner, Raissa
Klugmann, Matthias
Pape, Hans-Christian
Lutz, Beat
Title: Impaired 2-AG signaling in hippocampal glutamatergic neurons : aggravation of anxiety-like behavior and unaltered seizure susceptibility
Online publication date: 20-Jun-2022
Language: english
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: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY-NC
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Journal: The international journal of neuropsychopharmacology
Pages or article number: pyv091
Publisher: Oxford Univ. Press
Publisher place: Oxford
Issue date: 2016
ISSN: 1469-5111
Publisher URL:
Publisher DOI: 10.1093/ijnp/pyv091
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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