Significance of inhibitory recruitment in aging with preserved cognition: limiting gamma-aminobutyric acid type A α5 function produces memory impairment

Ming Teng Koh, Audrey Branch, Rebecca Haberman, Michela Gallagher

Research output: Contribution to journalArticle

Abstract

Numerous aging studies have identified a shift in the excitatory/inhibitory (E/I) balance with heightened hippocampal neural activity associated with age-related memory impairment across species, including rats, monkeys, and humans. Neurobiological investigations directed at the hippocampal formation have demonstrated that unimpaired aged rats performing on par with young adult rats in a spatial memory task exhibit gene expression profiles, mechanisms for plasticity, and altered circuit/network function, which are distinct from younger rats. Particularly striking is a convergence of observational evidence that aged unimpaired rats augment recruitment of mechanisms associated with neural inhibition, a finding that may represent an adaptive homeostatic adjustment necessary to maintain neural plasticity and memory function in aging. In this study, we test the effect of limiting inhibition via administration of TB21007, a negative allosteric modulator of the alpha 5 subtype of gamma-aminobutyric acid type A α5 receptor, on a radial arm maze assessment of memory function. Impaired memory performance produced by this intervention in otherwise high-performing aged rats supports an adaptive role for gamma-aminobutyric acid in the functional maintenance of intact cognition in aging.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalNeurobiology of Aging
Volume91
DOIs
StatePublished - Jul 2020

Keywords

  • Aging
  • GABA α5 receptor
  • Inhibition
  • Spatial memory

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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