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
Year of first publication:	2016
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
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7173
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY-NC
Information on rights of use:	https://creativecommons.org/licenses/by-nc/4.0/
Journal:	The international journal of neuropsychopharmacology 19 2
Pages or article number:	pyv091
Publisher:	Oxford Univ. Press
Publisher place:	Oxford
Issue date:	2016
ISSN:	1469-5111 1461-1457
Publisher URL:	http://dx.doi.org/10.1093/ijnp/pyv091
Publisher DOI:	10.1093/ijnp/pyv091
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)