Gutenberg Open Science: Cell type-specific genetic reconstitution of CB1 receptor subsets to assess their role in exploratory behaviour, sociability, and memory

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-6150

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DC Field	Value	Language
dc.contributor.author	De Giacomo, Vanessa	-
dc.contributor.author	Ruehle, Sabine	-
dc.contributor.author	Lutz, Beat	-
dc.contributor.author	Häring, Martin	-
dc.contributor.author	Remmers, Floortje	-
dc.date.accessioned	2022-02-25T08:44:14Z	-
dc.date.available	2022-02-25T08:44:14Z	-
dc.date.issued	2022	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/6159	-
dc.description.abstract	Several studies support the notion that exploratory behaviour depends on the functionality of the cannabinoid type 1 (CB1) receptor in a cell type-specific manner. Mice lacking the CB1 receptor in forebrain GABAergic or dorsal telencephalic glutamatergic neurons have served as essential tools revealing the necessary CB1 receptor functions in these two neuronal populations. However, whether these specific CB1 receptor populations are also sufficient within the endocannabinoid system for wild-type-like exploratory behaviour has remained unknown. To evaluate cell-type-specific sufficiency of CB1 receptor signalling exclusively in dorsal telencephalic glutamatergic neurons (Glu-CB1-RS) or in forebrain GABAergic neurons (GABA-CB1-RS), we utilised a mouse model in which CB1 receptor expression can be reactivated conditionally at endogenous levels from a complete CB1-KO background. The two types of conditional CB1-rescue mice were compared with CB1 receptor-deficient [no reactivation (Stop-CB1)] and wild-type [ubiquitous reactivation of endogenous CB1 receptor (CB1-RS)] controls to investigate the behavioural consequences. We evaluated social and object exploratory behaviour in four different paradigms. Remarkably, the reduced exploration observed in Stop-CB1 animals was rescued in Glu-CB1-RS mice and sometimes even surpassed CB1-RS (wild-type) exploration. In contrast, GABA-CB1-RS animals showed the lowest exploratory drive in all paradigms, with an even stronger phenotype than Stop-CB1 mice. Interestingly, these effects weakened with increasing familiarity with the environment, suggesting a causal role for altered neophobia in the observed phenotypes. Taken together, using our genetic approach, we were able to substantiate the opposing role of the CB1 receptor in dorsal telencephalic glutamatergic versus forebrain GABAergic neurons regarding exploratory behaviour.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY-NC-ND	*
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Cell type-specific genetic reconstitution of CB1 receptor subsets to assess their role in exploratory behaviour, sociability, and memory	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-6150	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	European journal of neuroscience	de
jgu.journal.volume	55	de
jgu.journal.issue	4	de
jgu.pages.start	939	de
jgu.pages.end	951	de
jgu.publisher.year	2022	-
jgu.publisher.name	Wiley	de
jgu.publisher.place	Oxford u.a.	de
jgu.publisher.issn	1460-9568	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1111/ejn.15069	de
jgu.organisation.ror	https://ror.org/023b0x485
Appears in collections:	JGU-Publikationen

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