Biology subjects

Brunswick, C. A.

Publications and source records attributed to Brunswick, C. A..

3 recordsLinked to original sources

bioRxiv2026

Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation

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.

neuroscience↗

bioRxiv2026

Old mice fail to integrate a memory update into an existing hippocampal engram.

Existing memories can be updated by the presentation of new information during memory retrieval. Memory updating is impaired with age, and recent reports indicate this process is more susceptible to age-related impairments than the formation of new memories. However, the neuronal mechanisms underlying age-related updating impairments are unknown. Here, we investigated how memory engrams within the dorsal hippocampus encode a memory update in the young and old brain. We found that old mice tended to re-engage a smaller proportion of the original memory engram during the update session and chemogenetically increasing the activation of this engram alleviated age-related updating deficits. A range of therapeutically relevant behavioral and pharmacological approaches promoting re-engagement of the training engram also improved memory updating in old mice. Together, these results identify a novel mechanism by which memory updating is impaired with age and expand our understanding of how the brain organizes related information.

neuroscience↗

bioRxiv2024

Pharmacological HDAC3 inhibition alters memory updating in young and old mice

Long-term memories are not stored in a stable state but must be flexible and dynamic to maintain relevance in response to new information. Existing memories are thought to be updated through the process of reconsolidation, in which memory retrieval initiates destabilization and updating to incorporate new information. Memory updating is impaired in old age, yet little is known about the mechanisms that go awry. One potential mechanism is the repressive histone deacetylase 3 (HDAC3), which is a powerful negative regulator of memory formation that contributes to age-related impairments in memory formation. Here, we tested whether HDAC3 also contributes to age-related impairments in memory updating using the Objects in Updated Locations (OUL) paradigm. We show that blocking HDAC3 immediately after updating with the pharmacological inhibitor RGFP966 ameliorated age-related impairments in memory updating in 18-m.o. mice. Surprisingly, we found that post-update HDAC3 inhibition in young (3-m.o.) mice had no effect on memory updating but instead impaired memory for the original information, suggesting that the original and updated information may compete for expression at test and HDAC3 helps regulate which information is expressed. To test this idea, we next assessed whether HDAC3 inhibition would improve memory updating in young mice given a weak, subthreshold update. Consistent with our hypothesis, we found that HDAC3 blockade strengthened the subthreshold update without impairing memory for the original information, enabling balanced expression of the original and updated information. Together, this research suggests that HDAC3 may contribute to age-related impairments in memory updating and may regulate the strength of a memory update in young mice, shifting the balance between the original and updated information at test.

neuroscience↗