Sensory and Motor Systems Modulation of a Single Neuron Has State- Dependent Actions on Circuit Dynamics1,2,3

When does neuromodulation of a single neuron influence the output of the entire network? We constructed a five-cell circuit in which a neuron is at the center of the circuit and the remaining neurons form two distinct oscillatory subnetworks. All neurons were modeled as modified MorrisLecar models with a hyperpolarization-activated conductance (gh) in addition to calcium (gCa), potassium (gK), and leak conductances. We determined the effects of varying gCa, gK, and gh on the frequency, amplitude, and duty cycle of a single neuron oscillator. The frequency of the single neuron was highest when the gK and gh conductances were high and gCa was moderate whereas, in the traditional MorrisLecar model, the highest frequencies occur when both gK and gCa are high. We randomly sampled parameter space to find 143 hub oscillators with nearly identical frequencies but with disparate maximal conductance, duty cycles, and burst amplitudes, and then embedded each of these hub neurons into networks with different sets of synaptic parameters. For one set of network parameters, circuit behavior was virtually identical regardless of the underlying conductances of the hub neuron. For a different set of network parameters, circuit behavior varied with the maximal conductances of the hub neuron. This demon-strates that neuromodulation of a single target neuron may dramatically alter the performance of an entire networ