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Transient potassium channels augment degeneracy in hippocampal active dendritic spectral tuning.

Rathour RK, Malik R, Narayanan R - Sci Rep (2016)

Bottom Line: Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map.Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk.Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

View Article: PubMed Central - PubMed

Affiliation: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.

ABSTRACT
Hippocampal pyramidal neurons express an intraneuronal map of spectral tuning mediated by hyperpolarization-activated cyclic-nucleotide-gated nonspecific-cation channels. Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map. To test this, we performed patch-clamp recordings from soma and dendrites of rat hippocampal pyramidal neurons, and measured spectral tuning before and after blocking KA channels using two structurally distinct pharmacological agents. Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk. Furthermore, across all measured locations, blocking KA channels enhanced temporal summation of postsynaptic potentials and critically altered the impedance phase profile, resulting in a significant reduction in total inductive phase. Finally, pair-wise correlations between intraneuronal percentage changes (after blocking KA channels) in different measurements were mostly weak, suggesting differential regulation of different physiological properties by KA channels. Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

No MeSH data available.


Related in: MedlinePlus

Blocking KA channels resulted in increased subthreshold intrinsic excitability and enhanced temporal summation across the somato-apical trunk.(a) Schematic of somato-apical trunk showing experimental setup for assessing the effect of blocking KA channels on various physiologically relevant measurements at various locations along the somato-apical trunk (up to ~300 μm). Local voltage responses at various locations along the somato-apical trunk were recorded in response to current stimuli injected through an electrode. Recording locations were binned into three sub-populations (soma, ~125 μm and ~250 μm) depending on their distance from the pyramidal cell layer, and the colored dots shown along the somato-apical trunk serve as codes for corresponding sub-populations in (b–j). (b,c) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (b) or 3,4-DAP (c), on Rin for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (d) Cumulative probability of percentage change in Rin in response to blocking A-type K+ channels using BaCl2 (top) or 3,4-DAP (bottom). (e) Population data for percentage change in Rin after blocking KA channels, using either BaCl2 (left) or 3,4-DAP (right), plotted as a function of recording location. Open circles represent individual cells and filled circles represent the average values (mean ± SEM). (f) Voltage traces recorded from dendrites located at 240 μm (top) and 270 μm (bottom) away from soma in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange), using BaCl2 (top) and 3,4-DAP (bottom), respectively. (g–j) Same as (b–e) for temporal summation strength, Sα. All measurements were obtained at −65 mV.
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f2: Blocking KA channels resulted in increased subthreshold intrinsic excitability and enhanced temporal summation across the somato-apical trunk.(a) Schematic of somato-apical trunk showing experimental setup for assessing the effect of blocking KA channels on various physiologically relevant measurements at various locations along the somato-apical trunk (up to ~300 μm). Local voltage responses at various locations along the somato-apical trunk were recorded in response to current stimuli injected through an electrode. Recording locations were binned into three sub-populations (soma, ~125 μm and ~250 μm) depending on their distance from the pyramidal cell layer, and the colored dots shown along the somato-apical trunk serve as codes for corresponding sub-populations in (b–j). (b,c) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (b) or 3,4-DAP (c), on Rin for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (d) Cumulative probability of percentage change in Rin in response to blocking A-type K+ channels using BaCl2 (top) or 3,4-DAP (bottom). (e) Population data for percentage change in Rin after blocking KA channels, using either BaCl2 (left) or 3,4-DAP (right), plotted as a function of recording location. Open circles represent individual cells and filled circles represent the average values (mean ± SEM). (f) Voltage traces recorded from dendrites located at 240 μm (top) and 270 μm (bottom) away from soma in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange), using BaCl2 (top) and 3,4-DAP (bottom), respectively. (g–j) Same as (b–e) for temporal summation strength, Sα. All measurements were obtained at −65 mV.

Mentions: KA channels have been shown to regulate neuronal input resistance (Rin) and action potential firing frequency of hippocampal CA1 pyramidal neuron somata20. However, it is not known if these somato-centric changes in excitability extend to dendritic locations, and if these changes in excitability extend to changes in temporal summation across the somatodendritic compartments. Given the high density of KA channels in CA1 pyramidal neuron dendrites21, and given that KA channels have been shown to regulate excitatory post synaptic potentials, EPSP21, we first explored the role of KA channels in regulating sub- and suprathreshold excitability across the somatoapical trunk of CA1 pyramidal neurons. To do this, we measured Rin, action potential firing frequency and temporal summation strength (Sα), before and after blocking KA channels (Fig. 1) using either 200 μM BaCl222 or 150 μM 3,4-DAP23 in separate experiments, from soma or dendrites (up to ~300 μm from the soma; all recordings in this study were performed at physiological temperatures) of CA1 pyramidal neurons. We first assessed the subthreshold measures of excitability, and found that blocking KA channels significantly increased Rin across the somato-dendritic axis (Figs 1d and 2b,c; Tables S1 and S2), with percentage changes not significantly different along the somato-dendritic axis (Fig. 2d,e, BaCl2: p = 0.88 and 3,4-DAP: p = 0.38, Kruskal-Wallis rank sum test).


Transient potassium channels augment degeneracy in hippocampal active dendritic spectral tuning.

Rathour RK, Malik R, Narayanan R - Sci Rep (2016)

Blocking KA channels resulted in increased subthreshold intrinsic excitability and enhanced temporal summation across the somato-apical trunk.(a) Schematic of somato-apical trunk showing experimental setup for assessing the effect of blocking KA channels on various physiologically relevant measurements at various locations along the somato-apical trunk (up to ~300 μm). Local voltage responses at various locations along the somato-apical trunk were recorded in response to current stimuli injected through an electrode. Recording locations were binned into three sub-populations (soma, ~125 μm and ~250 μm) depending on their distance from the pyramidal cell layer, and the colored dots shown along the somato-apical trunk serve as codes for corresponding sub-populations in (b–j). (b,c) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (b) or 3,4-DAP (c), on Rin for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (d) Cumulative probability of percentage change in Rin in response to blocking A-type K+ channels using BaCl2 (top) or 3,4-DAP (bottom). (e) Population data for percentage change in Rin after blocking KA channels, using either BaCl2 (left) or 3,4-DAP (right), plotted as a function of recording location. Open circles represent individual cells and filled circles represent the average values (mean ± SEM). (f) Voltage traces recorded from dendrites located at 240 μm (top) and 270 μm (bottom) away from soma in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange), using BaCl2 (top) and 3,4-DAP (bottom), respectively. (g–j) Same as (b–e) for temporal summation strength, Sα. All measurements were obtained at −65 mV.
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Related In: Results  -  Collection

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f2: Blocking KA channels resulted in increased subthreshold intrinsic excitability and enhanced temporal summation across the somato-apical trunk.(a) Schematic of somato-apical trunk showing experimental setup for assessing the effect of blocking KA channels on various physiologically relevant measurements at various locations along the somato-apical trunk (up to ~300 μm). Local voltage responses at various locations along the somato-apical trunk were recorded in response to current stimuli injected through an electrode. Recording locations were binned into three sub-populations (soma, ~125 μm and ~250 μm) depending on their distance from the pyramidal cell layer, and the colored dots shown along the somato-apical trunk serve as codes for corresponding sub-populations in (b–j). (b,c) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (b) or 3,4-DAP (c), on Rin for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (d) Cumulative probability of percentage change in Rin in response to blocking A-type K+ channels using BaCl2 (top) or 3,4-DAP (bottom). (e) Population data for percentage change in Rin after blocking KA channels, using either BaCl2 (left) or 3,4-DAP (right), plotted as a function of recording location. Open circles represent individual cells and filled circles represent the average values (mean ± SEM). (f) Voltage traces recorded from dendrites located at 240 μm (top) and 270 μm (bottom) away from soma in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange), using BaCl2 (top) and 3,4-DAP (bottom), respectively. (g–j) Same as (b–e) for temporal summation strength, Sα. All measurements were obtained at −65 mV.
Mentions: KA channels have been shown to regulate neuronal input resistance (Rin) and action potential firing frequency of hippocampal CA1 pyramidal neuron somata20. However, it is not known if these somato-centric changes in excitability extend to dendritic locations, and if these changes in excitability extend to changes in temporal summation across the somatodendritic compartments. Given the high density of KA channels in CA1 pyramidal neuron dendrites21, and given that KA channels have been shown to regulate excitatory post synaptic potentials, EPSP21, we first explored the role of KA channels in regulating sub- and suprathreshold excitability across the somatoapical trunk of CA1 pyramidal neurons. To do this, we measured Rin, action potential firing frequency and temporal summation strength (Sα), before and after blocking KA channels (Fig. 1) using either 200 μM BaCl222 or 150 μM 3,4-DAP23 in separate experiments, from soma or dendrites (up to ~300 μm from the soma; all recordings in this study were performed at physiological temperatures) of CA1 pyramidal neurons. We first assessed the subthreshold measures of excitability, and found that blocking KA channels significantly increased Rin across the somato-dendritic axis (Figs 1d and 2b,c; Tables S1 and S2), with percentage changes not significantly different along the somato-dendritic axis (Fig. 2d,e, BaCl2: p = 0.88 and 3,4-DAP: p = 0.38, Kruskal-Wallis rank sum test).

Bottom Line: Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map.Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk.Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

View Article: PubMed Central - PubMed

Affiliation: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.

ABSTRACT
Hippocampal pyramidal neurons express an intraneuronal map of spectral tuning mediated by hyperpolarization-activated cyclic-nucleotide-gated nonspecific-cation channels. Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map. To test this, we performed patch-clamp recordings from soma and dendrites of rat hippocampal pyramidal neurons, and measured spectral tuning before and after blocking KA channels using two structurally distinct pharmacological agents. Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk. Furthermore, across all measured locations, blocking KA channels enhanced temporal summation of postsynaptic potentials and critically altered the impedance phase profile, resulting in a significant reduction in total inductive phase. Finally, pair-wise correlations between intraneuronal percentage changes (after blocking KA channels) in different measurements were mostly weak, suggesting differential regulation of different physiological properties by KA channels. Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

No MeSH data available.


Related in: MedlinePlus