Cell Types, Network Homeostasis, and Pathological Compensation from a Biologically Plausible Ion Channel Expression Model

• Published in: Neuron (Cambridge, Mass.) Vol. 82; no. 4; pp. 809 - 821
• Main Authors: O’Leary, Timothy, Williams, Alex H., Franci, Alessio, Marder, Eve
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 21.05.2014; Elsevier Limited; Cell Press
• Subjects: Action Potentials; Animals; Computer Simulation; Gene expression; General Neuroscience; Homeostasis; Homeostasis - physiology; Human health sciences; Humans; Ion Channels; Ion Channels - metabolism; Models, Biological; Nerve Net - physiology; Nervous system; Neurologie; Neurology; Neurons; Neurons - classification; Neurons - pathology; Neurons - physiology; Neuroscience (all); Rodents; Sciences de la santé humaine
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2014.04.002

How do neurons develop, control, and maintain their electrical signaling properties in spite of ongoing protein turnover and perturbations to activity? From generic assumptions about the molecular biology underlying channel expression, we derive a simple model and show how it encodes an “activity set point” in single neurons. The model generates diverse self-regulating cell types and relates correlations in conductance expression observed in vivo to underlying channel expression rates. Synaptic as well as intrinsic conductances can be regulated to make a self-assembling central pattern generator network; thus, network-level homeostasis can emerge from cell-autonomous regulation rules. Finally, we demonstrate that the outcome of homeostatic regulation depends on the complement of ion channels expressed in cells: in some cases, loss of specific ion channels can be compensated; in others, the homeostatic mechanism itself causes pathological loss of function. •A simple biochemical model of ion channel expression can explain activity set points•Physiological cell types are encoded by ion channel expression rates•Variability and network homeostasis emerge from cell-autonomous regulation•Homeostatic mechanisms can cause pathological loss of function O’Leary et al. show how homeostatic plasticity arises from a simple model of ion channel regulation that generates cell types with biologically plausible cell-to-cell variability. Perturbations and deletions can often be compensated, but sometimes the homeostatic mechanism itself causes pathology.