Functional Imbalance of Anterolateral Entorhinal Cortex and Hippocampal Dentate/CA3 Underlies Age-Related Object Pattern Separation Deficits

Neuron. 2018 Mar 7;97(5):1187-1198.e4. doi: 10.1016/j.neuron.2018.01.039.

Abstract

The entorhinal cortex (EC) is among the earliest brain areas to deteriorate in Alzheimer's disease (AD). However, the extent to which functional properties of the EC are altered in the aging brain, even in the absence of clinical symptoms, is not understood. Recent human fMRI studies have identified a functional dissociation within the EC, similar to what is found in rodents. Here, we used high-resolution fMRI to identify a specific hypoactivity in the anterolateral EC (alEC) commensurate with major behavioral deficits on an object pattern separation task in asymptomatic older adults. Only subtle deficits were found in a comparable spatial condition, with no associated differences in posteromedial EC between young and older adults. We additionally linked this condition to dentate/CA3 hyperactivity, and the ratio of activity between the regions was associated with object mnemonic discrimination impairment. These results provide novel evidence of alEC-dentate/CA3 circuit dysfunction in cognitively normal aged humans.

Keywords: CA3; LEC; aging; alEC; dentate gyrus; entorhinal; fMRI; lateral entohrinal; memory; pattern separation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • CA3 Region, Hippocampal / diagnostic imaging
  • CA3 Region, Hippocampal / physiology*
  • Dentate Gyrus / diagnostic imaging
  • Dentate Gyrus / physiology*
  • Discrimination, Psychological / physiology*
  • Entorhinal Cortex / diagnostic imaging
  • Entorhinal Cortex / physiology*
  • Female
  • Humans
  • Male
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiology*
  • Photic Stimulation / methods
  • Young Adult