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http://doi.org/10.25358/openscience-7173
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 |
Erscheinungsdatum: | 2016 |
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 |
Enthalten in den Sammlungen: | DFG-OA-Publizieren (2012 - 2017) |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | ||
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impaired_2ag_signaling_in_hip-20220616160918345.pdf | 21.19 MB | Adobe PDF | Öffnen/Anzeigen |