Initiation of dendritic NMDA spikes co-regulated via distance-dependent and dynamic distribution of the spine number and morphology in neuron dendrites

Abstract

Dendritic spines are small membranous protrusions that receive synaptic inputs from other neurons, enabling the initiation of dendritic N-methyl-D-aspartic (NMDA) spikes and somatic action potentials. During learning and memory processes, both the number of spines on a dendrite and the morphology of individual spines are constantly changing. The individual influence of spine number and morphology on dendritic NMDA spikes has already been revealed, but the functional significance of the co-regulation of spine number and morphology on NMDA spikes remains elusive. Here, we systematically investigated the initiation of local dendritic NMDA spikes by the dynamic distributions of the spine number and morphology on single dendrites in reconstructed neuron models. Different from the traditional cognition, we found the threshold number of spines required to generate local dendrite NMDA spikes on distal dendrites is fewer than that on proximal ones, because the thinner distal dendrites own higher impedance. As for the spine morphology, the presence of more α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors on the spine leads to larger NMDA spikes rather than an increase in the spine dimension alone. Furthermore, we first suggested that a single dendrite containing spines with gradually increasing head diameters away from the soma could generate larger NMDA spikes than that irrational distribution of spine morphology containing spines with decreasing head diameters, which can be compensated by the increasing spine number. Complementarily, the distance-dependent distribution of spine number and morphology co-regulate the intension of dendritic NMDA spikes. These findings about the threshold for NMDA spikes provide novel insights into the role of the irrational dynamic distribution of the spine number and morphology in senescence and disease processes such as Alzheimer’s disease, schizophrenia, and Parkinson’s disease, which causes abnormal neuron firing.