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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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Fourier Spectrum of the Membrane Potential Fluctuations During the Delay Period in the Model for Three Different Strengths of the Na+ Window Current(A) θm = −22 mV, gd = 0.8 mS/cm2, Iapp = 4.9 μA/cm2; (B) θm = −24 mV, gd = 0.39 mS/cm2, Iapp = 3.23 μA/cm2; (C) θm = −28 mV, gd = 0.39 mS/cm2, Iapp = 1.25 μA/cm2.
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pcbi-0030156-g009: Fourier Spectrum of the Membrane Potential Fluctuations During the Delay Period in the Model for Three Different Strengths of the Na+ Window Current(A) θm = −22 mV, gd = 0.8 mS/cm2, Iapp = 4.9 μA/cm2; (B) θm = −24 mV, gd = 0.39 mS/cm2, Iapp = 3.23 μA/cm2; (C) θm = −28 mV, gd = 0.39 mS/cm2, Iapp = 1.25 μA/cm2.

Mentions: When the Na+ window current is small, the fixed point of the fast subsystem near the bifurcation at b = bHopf is “spiral,” i.e., small perturbations around it decay or grow in an oscillatory manner when b < bHopf or b > bHopf, respectively [8,21]. When noise is added, it excites this oscillatory mode, and therefore the membrane potential of the neuron displays sustained subthreshold oscillations (see Figures 7A and 7B and 9A and 9B). Similarly, oscillatory fluctuations induced by noise are observed during the interburst periods in the stuttering state.


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)

Fourier Spectrum of the Membrane Potential Fluctuations During the Delay Period in the Model for Three Different Strengths of the Na+ Window Current(A) θm = −22 mV, gd = 0.8 mS/cm2, Iapp = 4.9 μA/cm2; (B) θm = −24 mV, gd = 0.39 mS/cm2, Iapp = 3.23 μA/cm2; (C) θm = −28 mV, gd = 0.39 mS/cm2, Iapp = 1.25 μA/cm2.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0030156-g009: Fourier Spectrum of the Membrane Potential Fluctuations During the Delay Period in the Model for Three Different Strengths of the Na+ Window Current(A) θm = −22 mV, gd = 0.8 mS/cm2, Iapp = 4.9 μA/cm2; (B) θm = −24 mV, gd = 0.39 mS/cm2, Iapp = 3.23 μA/cm2; (C) θm = −28 mV, gd = 0.39 mS/cm2, Iapp = 1.25 μA/cm2.
Mentions: When the Na+ window current is small, the fixed point of the fast subsystem near the bifurcation at b = bHopf is “spiral,” i.e., small perturbations around it decay or grow in an oscillatory manner when b < bHopf or b > bHopf, respectively [8,21]. When noise is added, it excites this oscillatory mode, and therefore the membrane potential of the neuron displays sustained subthreshold oscillations (see Figures 7A and 7B and 9A and 9B). Similarly, oscillatory fluctuations induced by noise are observed during the interburst periods in the stuttering state.

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