A biophysical perspective on the resilience of neuronal excitability across timescales

Neuronal membrane excitability must be resilient to perturbations that can take place over timescales from milliseconds to months (or even years in long-lived animals). A great deal of attention has been paid to classes of homeostatic mechanisms that contribute to long-term maintenance of neuronal excitability through processes that alter a key structural parameter: the number of ion channel proteins present at the neuronal membrane. However, less attention has been paid to the self-regulating 'automatic' mechanisms that contribute to neuronal resilience by virtue of the kinetic properties of ion channels themselves. Here, we propose that these two sets of mechanisms are complementary instantiations of feedback control, together enabling resilience on a wide range of temporal scales. We further point to several methodological and conceptual challenges entailed in studying these processes - both of which involve enmeshed feedback control loops - and consider the consequences of these mechanisms of resilience. Membrane excitability is central to neuronal function, and neurons must be resilient to changes in its underlying parameters. In this Perspective article, Marom and Marder suggest that two complementary mechanisms contribute to the resilience of membrane excitability: rapid 'kinetic-based' regulation of ion channel proteins and slower homeostatic control of ion channel membrane densities.

Automated summary

Neuronal membrane excitability must be resilient to perturbations that can occur over various time scales. Two complementary mechanisms, namely dynamic parameter regulation and self-regulation based on ion channel kinetics, contribute to the resilience of membrane excitability. The study also highlights the challenges in studying these processes and the consequences of these resilience mechanisms.