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Edited by Edward E. Smith, Columbia University, New York, NY, and approved April 15, 2011 (received for review January 27, 2011)
Abstract
Converging data from rodents and humans have demonstrated an age-related decline in pattern separation abilities (the ability to discriminate among similar experiences). Several studies have proposed the dentate and CA3 subfields of the hippocampus as the potential locus of this change. Specifically, these studies identified rigidity in place cell remapping in similar environments in the CA3. We used high-resolution fMRI to examine activity profiles in the dentate gyrus and CA3 in young and older adults as stimulus similarity was incrementally varied. We report evidence for “representational rigidity” in older adults’ dentate/CA3 that is linked to behavioral discrimination deficits. Using ultrahigh-resolution diffusion imaging, we quantified both the integrity of the perforant path as well as dentate/CA3 dendritic changes and found that both were correlated with dentate/CA3 functional rigidity. These results highlight structural and functional alterations in the hippocampal network that predict age-related changes in memory function and present potential targets for intervention.
Footnotes
- 1To whom correspondence may be addressed. E-mail: yassa{at}jhu.edu or cestark{at}uci.edu.
Author contributions: M.A.Y. and C.E.L.S. designed research; M.A.Y., A.T.M., S.M.S., and C.E.L.S. performed research; M.A.Y., A.T.M., S.M.S., and C.E.L.S. analyzed data; and M.A.Y., A.T.M., and C.E.L.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1101567108/-/DCSupplemental.
Age-related memory deficits linked to circuit-specific disruptions in the hippocampus
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