• Open Access

A critical role for the glial-derived neuromodulator d-serine in the age-related deficits of cellular mechanisms of learning and memory

Authors

  • J. P. Mothet,

    Search for more papers by this author
    • *

      Present address: Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR 9040, 1 avenue de la Terrasse, Bat 32, 91198, Gif sur Yvette, France.

  • E. Rouaud,

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author
  • P.-M. Sinet,

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author
  • B. Potier,

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author
  • A. Jouvenceau,

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author
  • P. Dutar,

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author
  • C. Videau,

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author
  • J. Epelbaum,

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author
  • J.-M. Billard

    1. Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d’Alésia, 75014 Paris, France
    Search for more papers by this author


Dr J.-M. Billard, INSERM U549, 2 ter rue d’Alésia, 75014 Paris, France. Tel.: 33 1 40 78 86 47; fax: 33 1 45 80 72 93; e-mail: billard@broca.inserm.fr

Summary

Age-associated deficits in learning and memory are closely correlated with impairments of synaptic plasticity. Analysis of N-methyl-D-aspartate receptor (NMDAr)-dependent long-term potentiation (LTP) in CA1 hippocampal slices indicates that the glial-derived neuromodulator d-serine is required for the induction of synaptic plasticity. During aging, the content of d-serine and the expression of its synthesizing enzyme serine racemase are significantly decreased in the hippocampus. Impaired LTP and NMDAr-mediated synaptic potentials in old rats are rescued by exogenous d-serine. These results highlight the critical role of glial cells and presumably astrocytes, through the availability of d-serine, in the deficits of synaptic mechanisms of learning and memory that occur in the course of aging.

Ancillary