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Research Article

Age-related memory deficits linked to circuit-specific disruptions in the hippocampus

Michael A. Yassa, Aaron T. Mattfeld, Shauna M. Stark, and Craig E. L. Stark
  1. aDepartment of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, MD 21218;
  2. bDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697; and
  3. cCenter for Neurobiology of Learning and Memory, Irvine, CA 92697

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PNAS first published May 9, 2011; https://doi.org/10.1073/pnas.1101567108
Michael A. Yassa
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  • For correspondence: yassa@jhu.edu cestark@uci.edu
Aaron T. Mattfeld
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Shauna M. Stark
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Craig E. L. Stark
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  • For correspondence: yassa@jhu.edu cestark@uci.edu
  1. Edited by Edward E. Smith, Columbia University, New York, NY, and approved April 15, 2011 (received for review January 27, 2011)

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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.

  • medial temporal lobe
  • diffusion tensor imaging
  • functional MRI
  • generalization
  • pattern completion

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.

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Age-related memory deficits linked to circuit-specific disruptions in the hippocampus
Michael A. Yassa, Aaron T. Mattfeld, Shauna M. Stark, Craig E. L. Stark
Proceedings of the National Academy of Sciences May 2011, 201101567; DOI: 10.1073/pnas.1101567108

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Age-related memory deficits linked to circuit-specific disruptions in the hippocampus
Michael A. Yassa, Aaron T. Mattfeld, Shauna M. Stark, Craig E. L. Stark
Proceedings of the National Academy of Sciences May 2011, 201101567; DOI: 10.1073/pnas.1101567108
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