A novel mechanism for irregular firing of a neuron in response to periodic stimulation: irregularity in the absence of noise.

Irregular firing of action potentials (AP's) is a characteristic feature of neurons in the brain. The variability has been attributed to noise from various sources. This study illustrates an alternative mechanism, namely, deterministic irregularity within a model of ionic conductances. Specifically, a model based on modern measurements of the Na+ and K+ current components from the squid giant axon fires irregularly in response to a continuous train of near-threshold current pulses. The interspike interval histogram from these simulations is multi-modal, a result which in other systems has been attributed to stochastic resonance. Moreover, the simulations exhibited short burst of spikes followed by relatively long quiescent periods, a result suggestive of patterned input to the model even though the input consisted of a train of regularly spaced current pulses. The variability of firing is attributable to variations in AP parameters, in particular AP amplitude. The action potential for squid giant axons is not all-or-none. Rather, it is fundamentally a continuous function of stimulus amplitude. That is, the membrane lacks a threshold. Variation in AP amplitude, and to a lesser extent, AP duration, can produce variations in the time to a subsequent AP, which represents a paradigm shift for understanding irregular neuronal firing. The emphasis is not as much on events prior to an AP as it is on the AP's themselves.