Age-related effects of the neuromodulator D-serine on neurotransmission and synaptic potentiation in the CA1 hippocampal area of the rat |
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Authors: | Junjaud G Rouaud E Turpin F Mothet J-P Billard J-M |
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Affiliation: | Neurobiologie de la Croissance et de la Sénescence, INSERM, Faculté de Médecine, Université Paris-Descartes, Paris, France. |
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Abstract: | 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. |
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Keywords: | ageing glia glutamate hippocampus long-term potentiation synaptic plasticity |
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