Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation
- 1Pennsylvania State University
Abstract
Existing memories can be updated with new information through a process known as reconsolidation, though the molecular mechanisms underlying this process are poorly understood. Additionally, memory updating is impaired with aging, but little is known about how this impairment occurs. Here, we used a hippocampus-dependent memory updating task alongside transcriptomics to identify which genes are upregulated in the dorsal hippocampus specifically during a memory update in both young adult mice, which show successful memory updating, and in old mice, which do not. In young mice, we observed that distinct transcriptional programs were activated by reconsolidation-dependent memory updating and memory retrieval without new information. In old mice, similar transcriptional programs were engaged by both memory updating and memory retrieval. From our sequencing results, we identified Tent5a as a novel regulator of reconsolidation-mediated memory updating, and we demonstrate that hippocampal expression of Tent5a is necessary for this process. Together, these results expand our understanding of both the underlying transcriptional mechanisms of memory updating and how these mechanisms go awry in the aged brain.
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BibTeX
@misc{brunswick2026aging,
title = {{Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation}},
author = {C. A. Brunswick and A. G. Defina and T. A. Wood and A. Sebastian and A. R. McKenna and S. Murakami and P.-H. Chiu and S. M. Jordan and G. C. Pifer and I. Albert and J. L. Kwapis},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.750076},
url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750076v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation
AU - C. A. Brunswick
AU - A. G. Defina
AU - T. A. Wood
AU - A. Sebastian
AU - A. R. McKenna
AU - S. Murakami
AU - P.-H. Chiu
AU - S. M. Jordan
AU - G. C. Pifer
AU - I. Albert
AU - J. L. Kwapis
PY - 2026
DA - 2026/09/08
PB - bioRxiv
DO - 10.64898/2026.09.08.750076
UR - https://www.biorxiv.org/content/10.64898/2026.09.08.750076v1
AB - Existing memories can be updated with new information through a process known as reconsolidation, though the molecular mechanisms underlying this process are poorly understood. Additionally, memory updating is impaired with aging, but little is known about how this impairment occurs. Here, we used a hippocampus-dependent memory updating task alongside transcriptomics to identify which genes are upregulated in the dorsal hippocampus specifically during a memory update in both young adult mice, which show successful memory updating, and in old mice, which do not. In young mice, we observed that distinct transcriptional programs were activated by reconsolidation-dependent memory updating and memory retrieval without new information. In old mice, similar transcriptional programs were engaged by both memory updating and memory retrieval. From our sequencing results, we identified Tent5a as a novel regulator of reconsolidation-mediated memory updating, and we demonstrate that hippocampal expression of Tent5a is necessary for this process. Together, these results expand our understanding of both the underlying transcriptional mechanisms of memory updating and how these mechanisms go awry in the aged brain.
ER -