Loss of thin spines and small synapses contributes to defective hippocampal function in aged mice

Neurobiol Aging. 2018 Nov:71:91-104. doi: 10.1016/j.neurobiolaging.2018.07.010. Epub 2018 Jul 24.

Abstract

Aging is a normal physiological process associated with impairments in cognitive function, including learning and memory. Here, the underlying synaptic mechanisms by which aging leads to the decline of spatial learning and memory function were investigated in 25-month-old aged mice versus 2-month-old young mice. Deficits of spatial learning and memory, as well as selective loss of thin spines, but not mushroom-type spines on apical dendrites of CA1 pyramidal cells were found in aged mice. Specifically, loss of thin spines in aged mice with memory deficits was primarily found on dendritic segments located in the Schaffer pathway, and the density of thin spines significantly correlated with spatial memory performance. The loss of thin spines was evidenced by a decrease in small synapses that express diminutive amounts of postsynaptic density protein-95 and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1. Furthermore, mushroom-type spines and GluR1-expressed large synapses were not affected in aged mice with impaired memory. Taken together, these data suggest that the selective loss of those highly plastic thin spines with sparse postsynaptic density protein-95 and GluR1 receptors may significantly contribute to cognitive deficits in aged individuals.

Keywords: AMPA receptor; Aging; Hippocampus; Learning and memory; PSD-95; Spines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / physiology*
  • Dendritic Spines / physiology*
  • Male
  • Mice, Inbred C57BL
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology
  • Receptors, AMPA / metabolism
  • Spatial Learning / physiology*
  • Spatial Memory / physiology*
  • Synapses / physiology*

Substances

  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 1