Periodic Inward Currents Triggered by NMDA in Immature CA3 Hippocampal Neurones

Abstract

There is widespread interest in the function of N-methyl-D-aspartate (NMDA) receptors in the CNS, especially in the hippocampus where they are higly concentrated and may contribute to long term potentiation, a model of memory. More recent studies performed primarily in the visual system suggest a preferential involvement of NMDA receptors in developmental plasticity (Tsumoto et al., 1987; Kleinschmidt et al. 1987). Using a single electrode voltage clamp technique, we have found that NMDA generates slow inward currents in immature CA3 hippocampal neurones, already a few hours after birth, confirming that NMDA receptors are present and active very early in postnatal life. In addition, repeated applications of NMDA, initiated in immature (but not in adult) neurones, TTX-insensitive periodic inward currents (PICs), which persisted for hours as a prominent on-going phenomenon, whose frequency was independent of membrane potential. These currents were observed under conditions in which K⁺ conductances were much reduced by external Cs⁺, tetraethylammonium (TEA) or 4-aminopyridine (4-AP). Though TTX-insensitive, PICs appear to have a synaptic origin, since they were reduced by bicuculline and abolished by the excitatory amino acid antagonist kynurenic acid. It is suggested that NMDA may generate PICs by initiating in immature neurones periodic fluctuations of intracellular calcium, leading to pulsatile release of glutamate and GABA from nerve terminals.