Cell types, network homeostasis, and pathological compensation from a biologically plausible ion channel expression model.
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.
Volen Center and Biology Department, Brandeis University, Waltham, MA 02454, USA. Electronic address: toleary@brandeis.edu.
Timothy
T
O'Leary
Volen Center and Biology Department, Brandeis University, Waltham, MA 02454, USA.
Alex H
AH
Williams
Department of Electrical Engineering and Computer Science, University of Liège, 10 Grande Traverse, Liège B 4000, Belgium; Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK.
Alessio
A
Franci
Volen Center and Biology Department, Brandeis University, Waltham, MA 02454, USA. Electronic address: marder@brandeis.edu.
Eve
E
Marder
D000200:Action Potentials; D000818:Animals; D003198:Computer Simulation; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008954:Models, Biological; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000473:pathology / Q000502:physiology*
D007473:Ion Channels