Transient DREADD Manipulation of the Dorsal Dentate Gyrus in Rats Impairs Initial Learning of Place‐Outcome Associations

ABSTRACT The dentate gyrus subfield of the hippocampus is thought to be critically involved in the disambiguation of similar episodic experiences and places in a context‐dependent manner. However, most empirical evidence has come from lesion and gene knock‐out studies in rodents, in which the dentat...

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Vydáno v:	Hippocampus Ročník 35; číslo 3; s. e70014 - n/a
Hlavní autoři:	Lim, J., Souiki, A., Ahmad, P., Oomen, C. A., Huis in ’t Veld, G. J., Lansink, C. S., Pennartz, C. M. A., Olcese, U.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Hoboken, USA John Wiley & Sons, Inc 01.05.2025 Wiley Subscription Services, Inc
Témata:	Animals Association Learning - drug effects Association Learning - physiology Dentate gyrus Dentate Gyrus - drug effects Dentate Gyrus - physiology Discrimination Learning - drug effects Discrimination Learning - physiology DREADDs episodic memory hippocampus Learning Male place‐reward associations Rats Rats, Long-Evans Reinforcement Reward episodic memory place‐reward associations DREADDs dentate gyrus rats hippocampus
ISSN:	1050-9631, 1098-1063, 1098-1063
On-line přístup:	Získat plný text
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Shrnutí:	ABSTRACT The dentate gyrus subfield of the hippocampus is thought to be critically involved in the disambiguation of similar episodic experiences and places in a context‐dependent manner. However, most empirical evidence has come from lesion and gene knock‐out studies in rodents, in which the dentate gyrus is permanently perturbed and compensation of affected functions via other areas within the memory circuit could take place. The acute and causal role of the dentate gyrus herein remains therefore elusive. The present study aimed to investigate the acute role of the dorsal dentate gyrus in disambiguation learning using reversible inhibitory DREADDs. Rats were trained on a location discrimination task and learned to discriminate between a rewarded and unrewarded location with either small (similar condition) or large (dissimilar condition) separation. Reward contingencies switched after applying a reversal rule, allowing us to track the temporal engagement of the dentate gyrus during the task. Bilateral DREADD modulation of the dentate gyrus impaired the initial acquisition learning of place‐reward associations, but performance rapidly recovered to baseline levels within the same session. Modeling of the behavioral patterns revealed that reward sensitivity and alternation behavior were temporally associated with the DG‐dependent impairment during acquisition learning. Our study thus provides novel evidence that the dorsal dentate gyrus is acutely engaged during the initial acquisition learning of place‐reward associations.
Bibliografie:	Funding A. Souiki and P. Ahmad are contributed equally to this work. This work was supported by ZonMw and Amsterdam Neuroscience. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Funding: This work was supported by ZonMw and Amsterdam Neuroscience.
ISSN:	1050-9631 1098-1063 1098-1063
DOI:	10.1002/hipo.70014