Transcriptomic signatures of hippocampal active place avoidance memory maintenance.

Overview

1. School of Graduates Studies, Program in Neural and Behavioral Sciences, State University of New York, Downstate Health Sciences University, Brooklyn, NY, United States
2. Institute of Genomics in Health, State University of New York, Downstate Health Sciences University, Brooklyn, NY, United States
3. School of Graduates Studies, Program in Molecular and Cell Biology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, United States
4. Department of Pathology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, United States
5. The Robert F. Furchgott Center for Neural & Behavioral Science, State University of New York, Downstate Health Sciences University, Brooklyn, NY, United States
6. Department of Cell Biology, State University of New York, Downstate Health Sciences University, Brooklyn, NY, United States
7. Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, United States

Abstract

The gene expression changes associated with memory acquisition, consolidation and reconsolidation–all active epochs in memory formation–have been well characterized in the rodent hippocampus. Less is known, however, of the changes in gene expression during the offline maintenance of memory. In this study, we measured the gene expression changes in the dorsal hippocampus of four mice 3 days after consolidation of an active place avoidance memory. We examined gene expression changes in a putative subset of memory-associated neurons by leveraging the immediate early gene in vivo tagging system of the Arc-Cre/flox-eYFP transgenic mouse line. Through spatial transcriptomics we found that memory trained animals exhibited spatially regionalized expression of genes involved in post-synaptic function in CA1, synaptic vesicle transport in CA3, and neuronal differentiation in DG. Surprisingly, these gene expression enrichments were not observed in eYFP mRNA positive spatial spots. To gain granularity into this finding, we carried out single nuclear RNA sequencing, which confirmed enrichment of differentially expressed genes associated with synaptic plasticity and post-synaptic signaling unique to each subregion in trained animals, but not from their eYFP mRNA positive nuclei. Notably, nuclei of hippocampal neurons were largely characterized by their down regulation of genes involved in ATP synthesis and cytoplasmic translation. Our results suggest that two overarching transcriptomic patterns contribute to the functional changes in hippocampal cells during offline memory maintenance: regionally distributed expression of genes linked to synaptic functions (with concomitant sparseness of memory-associated neuronal ensembles) and a reduction of metabolic activity related genes across hippocampal sub-regions.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE330153, at NCBI GEO; found in “Data availability statement”

Data availability statement

The original contributions presented in the study are publicly available. This data can be found here: Spatial Transcriptomic s– GSE330153, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330153; Single Nuclei – GSE330161, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330161.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 6 authors, 8 keywords, 87 references.

Cite

This paper

Vingan, I., Phatarpekar, S., Tung, V. S. K., Hernández, A. I., Evgrafov, O. V., & Alarcon, J. M. (2026). Transcriptomic signatures of hippocampal active place avoidance memory maintenance. Frontiers in cellular neuroscience, 20, 1769317. https://doi.org/10.3389/fncel.2026.1769317

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