Age-related effects of the neuromodulator D-serine on neurotransmission and synaptic potentiation in the CA1 hippocampal area of the rat

J Neurochem. 2006 Aug;98(4):1159-66. doi: 10.1111/j.1471-4159.2006.03944.x. Epub 2006 Jun 21.


The effects of the co-agonist of the N-methyl-D-aspartate receptor (NMDAr) D-serine on glutamatergic neurotransmission and synaptic potentiation were studied in the CA1 hippocampal field of young (3-5 months old) and aged (25-27 months old) Sprague-Dawley rats using ex vivo extracellular electrophysiological recording techniques. Exogenous d-serine depressed fast neurotransmission mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate subtype of glutamate receptors in young but not in aged rats by acting on inhibitory glycinergic interneurons. In contrast, D-serine dose-dependently enhanced NMDAr-mediated synaptic responses in both groups of animals, but with a larger magnitude in aged rats, thus preventing the age-related decrease in NMDAr activation. D-serine also increased the magnitude of long-term potentiation in aged but not in young rats. Finally, D-serine levels were dramatically reduced in hippocampal tissues of aged rats. Taken together, these results indicate a weaker activation of the NMDAr glycine modulatory site by endogenous D-serine in aged animals, which accounts for a reduced NMDAr contribution to synaptic plasticity in ageing.

MeSH terms

  • Aging / physiology*
  • Animals
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Glutamic Acid / physiology
  • Glycine / physiology
  • Hippocampus / drug effects*
  • Long-Term Potentiation / drug effects*
  • Male
  • Nerve Net / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / drug effects
  • Receptors, Kainic Acid / drug effects
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Serine / pharmacology*
  • Synapses / drug effects*
  • Synaptic Transmission / drug effects*


  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Serine
  • Glycine