Modulations of dendritic Ca2+ spike with weak electric fields in layer 5 pyramidal cells.

Weak electric fields (EFs) modulate input/output function of pyramidal cells. Dendritic Ca2+ spike is an important cellular mechanism for coupling synaptic inputs from different cortical layers, which plays a critical role in neuronal computation. This study aims to understand the effects of weak EFs on Ca2+ spikes initiated in the distal dendrites. We use a computational model to simulate dendritic Ca2+ spikes and backpropagating action potentials (APs) in layer 5 pyramidal cells. We apply uniform EFs (less than 20 mV/mm) to the model and examine how they affect the threshold for activation of Ca2+ spikes. We show that the effects of weak field on synaptically evoked Ca2+ spikes depend on the timing of synaptic inputs. When distal inputs coincide with the onset of EFs within a time window of several milliseconds, field-induced depolarization facilitates the initiation of Ca2+ spikes, while field-induced hyperpolarization suppresses dendritic APs. Sustained field-induced depolarization leads to the inactivation of Ca2+ channels and increases the threshold of Ca2+ spike. Sustained field-induced hyperpolarization de-inactivates Ca2+ channels and reduces the threshold of Ca2+ spike. By altering the threshold of backpropagation activated Ca2+ firing, field-induced depolarization increases the degree of coupling between inputs of the soma and distal dendrites, while field-induced hyperpolarization results in a decrease of coupling. The modulatory effects of weak EF are governed by the field direction with respect to the cell. Our study explains a fundamental link between field-induced polarization, dendritic Ca2+ spike, and somato-dendritic coupling. The findings are crucial to interpret how weak EFs achieve specific modulation of cellular activity.