Predicting the response of striatal spiny neurons to sinusoidal input.

Spike-timing effects of small-amplitude sinusoidal currents were measured in mouse striatal spiny neurons firing repetitively. Spike-timing reliability varied with the stimulus frequency. For frequencies near the cell's firing rate, the cells altered firing rate to match the stimulus and became phase locked to it. The stimulus phase of firing during lock depended on the stimulus frequency relative to the cell's unperturbed firing rate. Interspike intervals during sinusoidal stimulation were predicted using an iterative map constructed from the cells' phase-resetting curve. Variability of interspike intervals was reduced by stimulation at all frequencies higher than about half the cell's unperturbed rate, and interspike intervals were accurately predicted by the map. Long sequences of spike times were predicted by iterating on the map. The accuracy of that prediction varied with frequency. Spike time predictability was highest near and during phase lock. The map predicted the phase of firing on the input and its dependence on stimulus frequency. Prediction errors, when they occurred, were of two kinds: unpredicted variation in interspike interval from intrinsic cell noise and accumulation of prediction errors from previous interspike intervals. Each type of prediction error arose from a different mechanism, and their impact was also predicted from the phase model. When two oscillatory input currents were presented simultaneously, striatal neurons responded selectively to only one of them, the one closest in frequency to the cell's unperturbed firing rate. Their spike times encoded the frequency and phase of that single oscillatory input. During repetitive firing, the timing of action potentials is determined by the interaction between the input and voltage-sensitive currents throughout the interspike interval. This interaction is encapsulated in the neuron's phase-resetting curve. The phase-resetting curve predicted spike timing to small sinusoidal currents over a wide range of stimulus frequencies. Firing patterns were most sensitive to oscillatory components near the cell's own firing rate, even in the presence of noise and other inputs.