Homeostatic regulation of neuronal activity: implications and feasibility of compartment-specific feedback

Abstract

Neurons regulate their average firing rate by adjusting their synaptic strength and intrinsic excitability. Intracellular calcium is implicated as an error signal for both types of homeostatic regulation. Past studies have focused on global calcium but two properties cannot be independently regulated by one error signal. Here, we computationally tested the implications of local vs global feedback and the feasibility of local (compartment-specific) error signals based on spatially segregated calcium changes. Simulations in a simple two-compartment model confirmed that a perturbation applied to one compartment induces local compensation only if feedback is compartment-specific. Simulations in a biophysically detailed multicompartment model with realistic calcium handling confirmed that dendritic and somatic calcium signals remain relatively segregated and can, therefore, encode separate error signals. Strong perturbations (as often tested experimentally) triggered widespread compensation because local compensation was overwhelmed. Non-local compensation also occurred when the spatial segregation of calcium signals was weakened. Our results demonstrate the plausibility of compartment-specific feedback using calcium-based error signals. Furthermore, whereas local homeostatic regulation nullifies local perturbations through compensation within the affected compartment, non-local regulation causes widespread compensatory changes that, while restoring the neurons overall input-output relationship, distorts the input-output relationship of individual compartments, with potentially important consequences.