Distance-Dependent Ni²⁺-Sensitivity of Synaptic Plasticity in Apical Dendrites of Hippocampal CA1 Pyramidal Cells

Abstract

Low concentration of Ni(2+), a T- and R-type voltage-dependent calcium channel (VDCC) blocker, is known to inhibit the induction of long-term potentiation (LTP) in the hippocampal CA1 pyramidal cells. These VDCCs are distributed more abundantly at the distal area of the apical dendrite than at the proximal dendritic area or soma. Therefore we investigated the relationship between the Ni(2+)-sensitivity of LTP induction and the synaptic location along the apical dendrite. Field potential recordings revealed that 25 microM Ni(2+) hardly influenced LTP at the proximal dendritic area (50 microM distant from the somata). In contrast, the same concentration of Ni(2+) inhibited the LTP induction mildly at the middle dendritic area (150 microM) and strongly at the distal dendritic area (250 microM). Ni(2+) did not significantly affect either the synaptic transmission at the distal dendrite or the burst-firing ability at the soma. However, synaptically evoked population spikes recorded near the somata were slightly reduced by Ni(2+) application, probably owing to occlusion of dendritic excitatory postsynaptic potential (EPSP) amplification. Even when the stimulating intensity was strengthened sufficiently to overcome such a reduction in spike generation during LTP induction, the magnitude of distal LTP was not significantly recovered from the Ni(2+)-dependent inhibition. These results suggest that Ni(2+) may inhibit the induction of distal LTP directly by blocking calcium influx through T- and/or R-type VDCCs. The differentially distributed calcium channels may play a critical role in the induction of LTP at dendritic synapses of the hippocampal pyramidal cells.