Reduced cognitive performance in aged rats correlates with increased excitation/inhibition ratio in the dentate gyrus in response to lateral entorhinal input

Neurobiol Aging. 2019 Oct:82:120-127. doi: 10.1016/j.neurobiolaging.2019.07.010. Epub 2019 Jul 23.


Aging often impairs cognitive functions associated with the medial temporal lobe (MTL). Anatomical studies identified the layer II pyramidal cells of the lateral entorhinal cortex (LEC) as one of the most vulnerable elements within the MTL. These cells provide a major excitatory input to the dentate gyrus hippocampal subfield through synapses onto granule cells and onto local inhibitory interneurons, and a fraction of these contacts are lost in aged individuals with impaired learning. Using optogenetics, we evaluated the functional status of the remaining inputs in an outbred rat model of aging that distinguishes between learning-impaired and learning-unimpaired individuals. We found that aging affects the presynaptic and postsynaptic strength of the LEC inputs onto granule cells. However, the magnitude of these changes was similar in impaired and unimpaired rats. In contrast, the recruitment of inhibition by LEC activation was selectively reduced in the aged impaired subjects. These findings are consistent with the notion that the preservation of an adequate balance of excitation and inhibition is crucial to maintaining proficient memory performance during aging.

Keywords: Disynaptic inhibition; E/I balance; Excitation/inhibition balance; Granule cells; Lateral entorhinal cortex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Cognitive Dysfunction / physiopathology*
  • Dentate Gyrus / chemistry
  • Dentate Gyrus / physiology*
  • Entorhinal Cortex / chemistry
  • Entorhinal Cortex / physiology*
  • Excitatory Postsynaptic Potentials / physiology*
  • Inhibitory Postsynaptic Potentials / physiology*
  • Male
  • Organ Culture Techniques
  • Rats
  • Rats, Long-Evans