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Aged rats with preserved memory dynamically recruit hippocampal inhibition in a local/global cue mismatch environment.

ABSTRACT: Similar to elderly humans, aged outbred Long-Evans rats exhibit individual differences in memory abilities, including a subset of aged rats that maintain memory function on par with young adults. Such individuals provide a basis for investigating mechanisms of resilience to age-related decline. The present study examined hippocampal gene expression in young adults and aged rats with preserved memory function under behavioral task conditions well established for assessing information processing central to the formation of episodic memory. Although behavioral measures and hippocampal gene induction associated with neural activity and synaptic plasticity were similar across age groups, a marker for inhibitory interneuron function in the hippocampal formation was distinctively increased only in aged rats but not in young adults. Because heightened hippocampal neural activity is associated with age-related memory impairment across species, including rats, monkeys, and humans, this finding may represent an adaptive homeostatic adjustment necessary to maintain neural plasticity and memory function in aging.

SUBMITTER: Branch A

PROVIDER: S-EPMC6392444 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Aged rats with preserved memory dynamically recruit hippocampal inhibition in a local/global cue mismatch environment.

Branch Audrey A Monasterio Amy A Blair Grace G Knierim James J JJ Gallagher Michela M Haberman Rebecca P RP

Neurobiology of aging 20190108

Similar to elderly humans, aged outbred Long-Evans rats exhibit individual differences in memory abilities, including a subset of aged rats that maintain memory function on par with young adults. Such individuals provide a basis for investigating mechanisms of resilience to age-related decline. The present study examined hippocampal gene expression in young adults and aged rats with preserved memory function under behavioral task conditions well established for assessing information processing c ...[more]

PMID: 30716540

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Project description:Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions. RNA profiles from cognitively unimpaired and impaired aged rats were compared under 2 conditions: spatial learning task and a non-spatial learning task.

Dataset Information

Aged rats with preserved memory dynamically recruit hippocampal inhibition in a local/global cue mismatch environment.

Publications

Aged rats with preserved memory dynamically recruit hippocampal inhibition in a local/global cue mismatch environment.

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