A MODEL NEURON WITH ACTIVITY-DEPENDENT CONDUCTANCES REGULATED BY MULTIPLE CALCIUM SENSORS

Membrane channels are subject to a wide variety of regulatory mechanis ms that can be affected by activity. WS present a model of a stomatoga stric ganglion (STG) neuron in which several Ca2+-dependent pathways a re used to regulate the maximal conductances of membrane currents in a n activity-dependent manner, Unlike previous models of this type, the regulation and modification of maximal conductances by electrical acti vity is unconstrained. The model has seven voltage-dependent membrane currents and uses three Ca2+ sensors acting on different time scales, Starting from random initial conditions over a given range, the model sets the maximal conductances for its active membrane currents to valu es that produce a predefined target pattern of activity similar to 90% of the time, In these models, the same pattern of electrical activity can be produced by a range of maximal conductances, and this range is compared with voltage-clamp data from the lateral pyloric neuron of t he STG, If the electrical activity of the model neuron is perturbed, t he maximal conductances adjust to restore the original pattern of acti vity, When the perturbation is removed, the activity pattern is again restored after a transient adjustment period, but the conductances may not return to their initial values, The model suggests that neurons m ay regulate their conductances to maintain fixed patterns of electrica l activity, rather than fixed maximal conductances, and that the regul ation process requires feedback systems capable of reacting to changes of electrical activity on a number of different time scales.