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Mechanisms of firing patterns in fast-spiking cortical interneurons.

Golomb D, Donner K, Shacham L, Shlosberg D, Amitai Y, Hansel D - PLoS Comput. Biol. (2007)

Bottom Line: In contrast, when the Na(+) window current is large, the neuron always fires tonically.We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their gd and in the strength of their Na(+) window current.We report experimental results from intracellular recordings supporting this prediction.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Ben-Gurion University, Be'er-Sheva, Israel. golomb@bgu.ac.il

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, gd, and it is delayed for larger gd. As gd 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 gd 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.

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Experimental Results: Fourier Spectrum of the Membrane Potential Fluctuations during Delay Periods in FS NeuronsTop: voltage time courses for three FS neurons exhibiting delayed firing.Bottom: the Fourier spectra of the subthreshold membrane potentials during the delay before spiking for these three neurons.(A) The minimal (just suprathreshold) firing frequency of this neuron is high (80 Hz). Pronounced subthreshold oscillations are observed during the delay period.(B) The minimal firing frequency of this neuron is lower than in (A) (38 Hz). The subthreshold oscillations exhibited by this neuron are less pronounced than in (A).(C) The minimal firing frequency of this neuron (4.3 Hz) is much lower than in (A) or (B). This neuron does not exhibit subthreshold oscillations during the delay period. Spectra were calculated over the time intervals denoted by the horizontal bars in the top panels.
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pcbi-0030156-g012: Experimental Results: Fourier Spectrum of the Membrane Potential Fluctuations during Delay Periods in FS NeuronsTop: voltage time courses for three FS neurons exhibiting delayed firing.Bottom: the Fourier spectra of the subthreshold membrane potentials during the delay before spiking for these three neurons.(A) The minimal (just suprathreshold) firing frequency of this neuron is high (80 Hz). Pronounced subthreshold oscillations are observed during the delay period.(B) The minimal firing frequency of this neuron is lower than in (A) (38 Hz). The subthreshold oscillations exhibited by this neuron are less pronounced than in (A).(C) The minimal firing frequency of this neuron (4.3 Hz) is much lower than in (A) or (B). This neuron does not exhibit subthreshold oscillations during the delay period. Spectra were calculated over the time intervals denoted by the horizontal bars in the top panels.

Mentions: The responses to steps of depolarizing current pulses were recorded intracellularly in FS neurons (n = 20, average ratio of the spike's rising phase dV/dt to falling phase dV/dt = 1.17 ± 0.29), as described in the section “Whole cell recordings and analysis” in Materials and Methods. Eight neurons responded to the depolarization onset almost instantaneously with a tonic non-adapting spike train. The other 60% of the neurons (n = 12) displayed a prolonged delay period, which was preceded by a transient firing of 1–3 spikes in some cases (Figure 11A and B), similar to the simulations of our model for low Na+ window current (Figure 7C). One cell from this group of 12 cells fired irregularly (Figure 11C). Eight out of those 12 cells had properties as reported in previous experimental studies of FS neurons (see also [22,25]). These eight cells exhibited a delay period followed by a tonic, high-frequency regular discharge (Figure 11A) or stuttering discharge with large, instantaneous intra-burst firing rate (Fig 11B). The minimal average firing frequencies in this group of neurons ranged from 25 to 220 Hz (average 81 ± 59 Hz) and the voltage threshold to action potential was −31.6 ± 5.0 mV. All the computed trial-average power spectra of the membrane fluctuations during the delay period (n = 4) displayed a peak within the gamma range (20–100 Hz). Two examples are shown in Figure 12A and 12B. These features are similar to those exhibited by our model neuron for small window current (Figure 9A and 9B).


Mechanisms of firing patterns in fast-spiking cortical interneurons.

Golomb D, Donner K, Shacham L, Shlosberg D, Amitai Y, Hansel D - PLoS Comput. Biol. (2007)

Experimental Results: Fourier Spectrum of the Membrane Potential Fluctuations during Delay Periods in FS NeuronsTop: voltage time courses for three FS neurons exhibiting delayed firing.Bottom: the Fourier spectra of the subthreshold membrane potentials during the delay before spiking for these three neurons.(A) The minimal (just suprathreshold) firing frequency of this neuron is high (80 Hz). Pronounced subthreshold oscillations are observed during the delay period.(B) The minimal firing frequency of this neuron is lower than in (A) (38 Hz). The subthreshold oscillations exhibited by this neuron are less pronounced than in (A).(C) The minimal firing frequency of this neuron (4.3 Hz) is much lower than in (A) or (B). This neuron does not exhibit subthreshold oscillations during the delay period. Spectra were calculated over the time intervals denoted by the horizontal bars in the top panels.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1941757&req=5

pcbi-0030156-g012: Experimental Results: Fourier Spectrum of the Membrane Potential Fluctuations during Delay Periods in FS NeuronsTop: voltage time courses for three FS neurons exhibiting delayed firing.Bottom: the Fourier spectra of the subthreshold membrane potentials during the delay before spiking for these three neurons.(A) The minimal (just suprathreshold) firing frequency of this neuron is high (80 Hz). Pronounced subthreshold oscillations are observed during the delay period.(B) The minimal firing frequency of this neuron is lower than in (A) (38 Hz). The subthreshold oscillations exhibited by this neuron are less pronounced than in (A).(C) The minimal firing frequency of this neuron (4.3 Hz) is much lower than in (A) or (B). This neuron does not exhibit subthreshold oscillations during the delay period. Spectra were calculated over the time intervals denoted by the horizontal bars in the top panels.
Mentions: The responses to steps of depolarizing current pulses were recorded intracellularly in FS neurons (n = 20, average ratio of the spike's rising phase dV/dt to falling phase dV/dt = 1.17 ± 0.29), as described in the section “Whole cell recordings and analysis” in Materials and Methods. Eight neurons responded to the depolarization onset almost instantaneously with a tonic non-adapting spike train. The other 60% of the neurons (n = 12) displayed a prolonged delay period, which was preceded by a transient firing of 1–3 spikes in some cases (Figure 11A and B), similar to the simulations of our model for low Na+ window current (Figure 7C). One cell from this group of 12 cells fired irregularly (Figure 11C). Eight out of those 12 cells had properties as reported in previous experimental studies of FS neurons (see also [22,25]). These eight cells exhibited a delay period followed by a tonic, high-frequency regular discharge (Figure 11A) or stuttering discharge with large, instantaneous intra-burst firing rate (Fig 11B). The minimal average firing frequencies in this group of neurons ranged from 25 to 220 Hz (average 81 ± 59 Hz) and the voltage threshold to action potential was −31.6 ± 5.0 mV. All the computed trial-average power spectra of the membrane fluctuations during the delay period (n = 4) displayed a peak within the gamma range (20–100 Hz). Two examples are shown in Figure 12A and 12B. These features are similar to those exhibited by our model neuron for small window current (Figure 9A and 9B).

Bottom Line: In contrast, when the Na(+) window current is large, the neuron always fires tonically.We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their gd and in the strength of their Na(+) window current.We report experimental results from intracellular recordings supporting this prediction.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Ben-Gurion University, Be'er-Sheva, Israel. golomb@bgu.ac.il

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, gd, and it is delayed for larger gd. As gd 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 gd 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.

Show MeSH
Related in: MedlinePlus