NMDA receptors of dentate gyrus granule cells participate in synaptic transmission following kindling

Abstract

In the mammalian central nervous system, receptors for the excitatory amino-acid neurotransmitters are divided into three subtypes depending on their sensitivity to three specific agonists: kainate, quisqualate and N-methyl-D-aspartate (NMDA)¹. The ionophores operated by NMDA are gated by Mg²⁺ in a voltage-dependent manner^2–4 and allow passage of several cations, including Ca²⁺ (refs 5,6) which may be important in plastic alterations of neuronal excitability. Indeed, specific antagonists of NMDA receptors effectively block spatial learning⁷, long-term potentiation^7,8 and some animal models of chronic epilepsy^9,10. Despite their abundance on central neurons¹¹, NMDA receptors, with a few noteworthy exceptions^12,13, do not generally seem to be involved in low-frequency synaptic transmission¹⁴. Here we report for the first time that NMDA receptors of the dentate gyms, where they do not normally contribute to the generation of synaptic potentials^7,15,16, become actively involved in synaptic transmission following long-lasting neuronal changes induced by daily electrical stimulation (kindling)¹⁷ of the amygdala or hippocampal commissures. In contrast to controls, the excitatory postsynaptic potentials (e.p.s.ps) of granule cells in hippocampal slices obtained from kindled animals displayed characteristics typical of an NMDA-receptor-mediated component. The involvement of NMDA receptors in synaptic transmission may underlie the long-lasting changes in neuronal function induced by kindling.