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bioRxiv · 10.1101/2025.03.07.641976

Distinct representations of an anxiogenic environment in different cell types of the ventral hippocampus

Berry, J. E.·Jimenez, J.·Chang, W.-l.·Ogbu, K. M.·Manfred, N.·Tegang, K.·Fusi, S.·Hen, R.·Lacefield, C.
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Abstract

In addition to its role in episodic memory and spatial navigation, the hippocampus has also been found to influence mood-related disorders such as anxiety and depression. These seemingly distinct roles are consistent with a functional dissociation between the two anatomical poles of the hippocampus: whereas the dorsal portion of the hippocampus in rodents is necessary for spatial tasks, the ventral portion controls affective behaviors. We have recently found that neurons in the ventral, but not dorsal, CA1 area of mice encode anxiety-related information (i.e. are "anxiety cells") in diverse defensive and exploratory behaviors. Still it is unclear how general threat-related information is computed within the hippocampal circuit. In this work, we have examined how distinct hippocampal subregions and cell types encode anxiety-related information by imaging calcium activity in large populations of genetically-defined neurons in the ventral hippocampus while mice explore the elevated plus maze (EPM), a conflict-based anxiety test. We compared the neural encoding of task-related features within the ventral CA1 (vCA1) and ventral dentate gyrus (vDG) regions in order to examine the emergence of anxiety-related activity through the hippocampal circuit. We found that granule cells (vGCs) of the vDG represented similar valence information to neurons in vCA1 in the form of arm-type specific encoding in the EPM, which suggests that encoding of anxiety-related features is already present at this first stage of hippocampal processing. When compared with ventral granule cells (vGCs), ventral mossy cells (vMCs) underlying the DG had stronger spatial encoding and less valence encoding, suggesting that they may be more functionally connected with the highly spatially sensitive dorsal hippocampus. Together these findings will help to understand the encoding of anxiety-related information in the hippocampus and how it relates to neural circuit defects in mood-related disorders.

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Berry, J. E., Jimenez, J., Chang, W.-l., Ogbu, K. M., Manfred, N., Tegang, K., Fusi, S., Hen, R., Lacefield, C.. 2025-03-10. Distinct representations of an anxiogenic environment in different cell types of the ventral hippocampus. https://doi.org/10.1101/2025.03.07.641976

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