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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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Dependence of the Delay Duration tdelay on the Amplitude of the Current Step Iapp(A) θm = −24 mV.(B) θm = −28 mV. In the two panels, gd = 0.39 mS/cm2. Solid lines: noiseless input (D = 0). Dashed lines: noisy input with variance D = 0.01 μA2 × ms/cm4. The delay duration was averaged over 50 trials. Gray lines represent one standard deviation around the mean value of tdelay for noisy input.
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pcbi-0030156-g004: Dependence of the Delay Duration tdelay on the Amplitude of the Current Step Iapp(A) θm = −24 mV.(B) θm = −28 mV. In the two panels, gd = 0.39 mS/cm2. Solid lines: noiseless input (D = 0). Dashed lines: noisy input with variance D = 0.01 μA2 × ms/cm4. The delay duration was averaged over 50 trials. Gray lines represent one standard deviation around the mean value of tdelay for noisy input.

Mentions: Figure 4A and 4B (solid lines) displays the dependency of the delay duration, tdelay, on Iapp for θm = −24 mV and θm = −28 mV, respectively (gd = 0.39 mS/cm2). In both cases, a delay in the spike response occurs within a restricted range of Iapp. Its duration, which is a decreasing function of Iapp, goes to infinity at firing threshold and jumps discontinuously to zero when Iapp becomes too large. Note that the divergence near threshold is sharper for θm = −28 mV than for θm = −24 mV. We will come back to this point later.


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)

Dependence of the Delay Duration tdelay on the Amplitude of the Current Step Iapp(A) θm = −24 mV.(B) θm = −28 mV. In the two panels, gd = 0.39 mS/cm2. Solid lines: noiseless input (D = 0). Dashed lines: noisy input with variance D = 0.01 μA2 × ms/cm4. The delay duration was averaged over 50 trials. Gray lines represent one standard deviation around the mean value of tdelay for noisy input.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0030156-g004: Dependence of the Delay Duration tdelay on the Amplitude of the Current Step Iapp(A) θm = −24 mV.(B) θm = −28 mV. In the two panels, gd = 0.39 mS/cm2. Solid lines: noiseless input (D = 0). Dashed lines: noisy input with variance D = 0.01 μA2 × ms/cm4. The delay duration was averaged over 50 trials. Gray lines represent one standard deviation around the mean value of tdelay for noisy input.
Mentions: Figure 4A and 4B (solid lines) displays the dependency of the delay duration, tdelay, on Iapp for θm = −24 mV and θm = −28 mV, respectively (gd = 0.39 mS/cm2). In both cases, a delay in the spike response occurs within a restricted range of Iapp. Its duration, which is a decreasing function of Iapp, goes to infinity at firing threshold and jumps discontinuously to zero when Iapp becomes too large. Note that the divergence near threshold is sharper for θm = −28 mV than for θm = −24 mV. We will come back to this point later.

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