Influence of subthreshold nonlinearities on signal-to-noise ratio and timing precision for small signals in neurons: Minimal model analysis

Subthreshold voltage- and time-dependent conductances can subserve different roles in signal integration and action potential generation. Here, we use minimal models to demonstrate how a non-inactivating low-threshold outward current (I_KLT) can enhance the precision of small-signal integration. Our integrate-and-fire models have only a few biophysical parameters, enabling a parametric study of I_KLT's effects. I_KLT increases the signal-to-noise ratio (SNR) for firing when a subthreshold 'signal' EPSP is delivered in the presence of weak random input. The increased SNR is due to the suppression of spontaneous firings to random input. In accordance, SNR grows as the EPSP amplitude increases. SNR also grows as the unitary synaptic current's time constant increases, leading to more effective suppression of spontaneous activity. Spike-triggered reverse correlation of the injected current indicates that, to reach spike threshold, a cell with I_KLT requires a briefer time course of injected current. Consistent with this narrowed integration time window, I_KLT enhances phase-locking, measured as vector strength, to a weak noisy and periodically modulated stimulus. Thus subthreshold negative feedback mediated by I_KLT enhances temporal processing. An alternative suppression mechanism is voltage- and time-dependent inactivation of a low-threshold inward current. This feature in an integrate-and-fire model also shows SNR enhancement, in comparison with a case when the inward current is non-inactivating. Small-signal detection can be significantly improved in noisy neuronal systems by subthreshold negative feedback, serving to suppress false positives.