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+, delayed-rectifier K+, and slowly inactivating d-type K+ conductances. The model is analyzed using nonlinear dynamical system theory. For small Na+ 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+ 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+ 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.

Increasing motor neuron excitability to treat weakness in sepsis

“…Irregular motor neuron firing induced by sepsis was closely associated with high frequency (>100 Hz) membrane potential oscillations between spikes (Fig 1). Irregular firing associated with high frequency membrane potential oscillations has been previously described in a variety of neuron types 18, 19 , including mouse motor neurons 14, 20 . In sodium pentobarbitone anesthetized mice, irregular firing and membrane potential oscillations are seen in motor neurons during slow triangular ramps of current injection when current intensity is just suprathreshold 14, 20 .…”

“…Oscillations in membrane potential during firing are thought to reflect the competing influence of inward and outward currents mediated by fast, voltage-dependent currents that are activated in the subthreshold range 14, 18–20 . As subthreshold currents serve to drive the motor neuron to action potential threshold, the finding of oscillations suggested that dysregulation of subthreshold currents might be the mechanism underlying the defect in motor neuron repetitive firing induced by sepsis.…”

Striatal Fast-Spiking Interneurons: From Firing Patterns to Postsynaptic Impact

“…Some experiments were also performed with a model neuron that produced tonic discharge ( θ m  = −28 mV, g KD  = 0.39 mS/cm 2 , see Figures A2 and A3 in Appendix). To induce oscillatory fluctuations in the subthreshold membrane potential during the interburst episodes, a Gaussian white noise current with zero mean and 15 pA SD (0.1 ms time step) was applied to the model neuron (Golomb et al, 2007). …”

Two functional inhibitory circuits are comprised of a heterogeneous population of fast-spiking cortical interneurons

“…Previous work has shown that high variable electrophysiological properties result from the combined activity of different membrane ion channels (Llinas, 1988) and cell morphology (Mainen et al, 1996). Among those ion channels, the voltage gated potassium channel Kv1 family plays an important role in action potential initiation at near threshold potentials and also serves to suppress action potential firing (Coetzee et al, 1999, Golomb et al, 2007). Additionally, Kvβ1 is an auxiliary subunit that forms complexes with the Kv1 family of ion channels leading to fast inactivation of evoked currents in heterozygous expression systems (Pongs et al, 1999).…”