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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 altered impedance phase and resulted in a decrease in total inductive phase across the somatoapical trunk.(a) Same as Fig. 2a. (b) Impedance phase plotted as functions of input current frequency derived from corresponding color-matched traces shown in Fig. 4a, under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) or 3,4-DAP (bottom). (c,d) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (c) or 3,4-DAP (d), on ΦL for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (e) Cumulative probability of percentage change in ΦL in response to blocking A-type K+ channels using BaCl2 (left) or 3,4-DAP (right). (f) Population data for percentage change in ΦL 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). All measurements were obtained at −65 mV.
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f5: Blocking KA channels altered impedance phase and resulted in a decrease in total inductive phase across the somatoapical trunk.(a) Same as Fig. 2a. (b) Impedance phase plotted as functions of input current frequency derived from corresponding color-matched traces shown in Fig. 4a, under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) or 3,4-DAP (bottom). (c,d) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (c) or 3,4-DAP (d), on ΦL for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (e) Cumulative probability of percentage change in ΦL in response to blocking A-type K+ channels using BaCl2 (left) or 3,4-DAP (right). (f) Population data for percentage change in ΦL 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). All measurements were obtained at −65 mV.

Mentions: Turning to phase response dynamics (Fig. 5b), we found that blocking KA channels lead to a decrease in total inductive phase, ΦL18, at various locations along the somato-dendritic axis (Fig. 5c,d) (Tables S1 and S2) with percentage changes in this reduction very similar across all somato-apical locations (Fig. 5e,f, BaCl2: p = 0.15 and 3,4-DAP: p = 0.29 Kruskal-Wallis rank sum test). Together, our results demonstrate a critical role for KA channels in regulating theta-frequency spectral tuning and in frequency-dependent intrinsic phase response of hippocampal pyramidal neuron somata and dendrites. Importantly, the impact of two structurally distinct KA-channel blockers, BaCl2 and 3,4-DAP, resulted in very similar results (both qualitatively and quantitatively) in terms of the excitability (Figs 2 and 3) and frequency-dependent measurements (Figs 4 and 5), thereby strengthening our conclusions about the role of KA channels (Tables S1 and S2).


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

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

Blocking KA channels altered impedance phase and resulted in a decrease in total inductive phase across the somatoapical trunk.(a) Same as Fig. 2a. (b) Impedance phase plotted as functions of input current frequency derived from corresponding color-matched traces shown in Fig. 4a, under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) or 3,4-DAP (bottom). (c,d) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (c) or 3,4-DAP (d), on ΦL for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (e) Cumulative probability of percentage change in ΦL in response to blocking A-type K+ channels using BaCl2 (left) or 3,4-DAP (right). (f) Population data for percentage change in ΦL 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). All measurements were obtained at −65 mV.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837398&req=5

f5: Blocking KA channels altered impedance phase and resulted in a decrease in total inductive phase across the somatoapical trunk.(a) Same as Fig. 2a. (b) Impedance phase plotted as functions of input current frequency derived from corresponding color-matched traces shown in Fig. 4a, under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) or 3,4-DAP (bottom). (c,d) Population data (also depicted as quartiles) for the effect of blocking KA channels, using BaCl2 (c) or 3,4-DAP (d), on ΦL for the three sub-populations of recording locations. *p < 0.05 Mann Whitney U test. (e) Cumulative probability of percentage change in ΦL in response to blocking A-type K+ channels using BaCl2 (left) or 3,4-DAP (right). (f) Population data for percentage change in ΦL 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). All measurements were obtained at −65 mV.
Mentions: Turning to phase response dynamics (Fig. 5b), we found that blocking KA channels lead to a decrease in total inductive phase, ΦL18, at various locations along the somato-dendritic axis (Fig. 5c,d) (Tables S1 and S2) with percentage changes in this reduction very similar across all somato-apical locations (Fig. 5e,f, BaCl2: p = 0.15 and 3,4-DAP: p = 0.29 Kruskal-Wallis rank sum test). Together, our results demonstrate a critical role for KA channels in regulating theta-frequency spectral tuning and in frequency-dependent intrinsic phase response of hippocampal pyramidal neuron somata and dendrites. Importantly, the impact of two structurally distinct KA-channel blockers, BaCl2 and 3,4-DAP, resulted in very similar results (both qualitatively and quantitatively) in terms of the excitability (Figs 2 and 3) and frequency-dependent measurements (Figs 4 and 5), thereby strengthening our conclusions about the role of KA channels (Tables S1 and S2).

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