Mechanisms of Firing Patterns in Fast-Spiking Cortical Interneurons

Abstract

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na, and slowly inactivating d-type K þ conductances. The model is analyzed using nonlinear dynamical system theory. For small Na þ window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, g d , and it is delayed for larger g d . As g d further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na þ window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their g d and in the strength of their Na þ window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction.

Origin of intrinsic irregular firing in cortical interneurons

“…They also observe subthreshold oscillations. The switching mechanism described here could also occur in this more complex model (37).…”

“…In a study of the firing of interneurons using a biophysical model of interneurons including g Na , the persistent Na + conductance g NAp , g KDR , and g Kd , both the window current and the total g Kd conductance shaped the spiking behavior of the model neurons (37). In this model, a large g Kd and a small window current were necessary for irregular firing.…”

Pyramidal Neurons Switch From Integrators In Vitro to Resonators Under In Vivo-Like Conditions

“…Pfeuty et al (2003) specifically concluded that potassium currents promote synchrony, whereas persistent sodium current impedes synchrony, which is consistent with our results insofar as outward current encourages class 2 excitability, whereas inward current encourages class 1 excitability. Golomb et al (2007) recently showed that increasing the sodium window current (which contributes inward current at perithreshold potentials) changed the bifurcation mechanism and prevented subthreshold voltage fluctuations, consistent with inward current switching the excitability of their model neuron to class 1. Hutcheon et al (1996) also showed through modeling that shunting could encourage resonance, although they attributed that effect to a quantitative change in the membrane time constant rather than a qualitative change in spike-initiating mechanism.…”

The influence of subthreshold membrane potential oscillations and GABAergic input on firing activity in striatal fast-spiking neurons

“…Striatal fast-spiking interneurons, which constitute approximately 1-2% of all striatal neurons, show many similarities to cortical fast-spiking cells. In response to somatic current injection, for example, some of these neurons exhibit spike bursts with a variable number of action potentials (so called stuttering) [2][3][4]. Interestingly, the membrane potential between such stuttering episodes oscillates in the range of 20-100 Hz [3,5].…”

“…Here we investigate the possible role of subthreshold oscillations on the synchronization of sub-and suprathreshold activity in a model of electrically coupled fast-spiking neurons. We use the model of Golomb et al [3], which we extended with a dendritic tree so as to be able to simulate distal synaptic input. We show that gap junctions are able to synchronize subthreshold membrane potential fluctuations in response to somatic current injection.…”