Elsevier

Brain Research

Volume 530, Issue 1, 15 October 1990, Pages 142-146
Brain Research

NMDA depolarizations and long-term potentiation are reduced in the aged rat neocortex

https://doi.org/10.1016/0006-8993(90)90671-WGet rights and content

Abstract

N-Methyl-d-aspartate (NMDA) responses were recorded intracellularly in layer V neocortical neurons in in vitro slices taken from young (4–6 months) and aged (27–29 months) Fischer 344 rats. Increasing amounts of NMDA produced membrane depolarizations in both groups of cells. The regression analysis showed significantly reduced sensitivity to NMDA in old neurons compared to young. A significant long-term potentiation of the field potential evoked by subcortical white matter stimulation was present in young but not in old slices. These results suggest that aging results in a decreased sensitivity to NMDA and impaired synaptic plasticity in the neocortex.

References (26)

  • WilsonD.A. et al.

    The postnatal development of post-activation potentiation in the rat neocortex

    Dev. Brain Res.

    (1983)
  • ArtolaA. et al.

    Long-term potentiation and NMDA receptors in rat visual cortex

    Nature

    (1987)
  • BarnesC.A.

    Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat

    J. Comp. Physiol. Psychol.

    (1979)
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    This work was supported by the Ontario Mental Health Foundation and Medical Research Council of Canada. Authors wish to thank Dr. Martin Wojtowicz for his valuable suggestions and criticisms.

    *

    Present address: Faculty of Medicine, Memorial University of Newfoundland, St. John's Newfoundland A1B 3V6, Canada.

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