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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

Typical experiment demonstrating the regulation of neuronal excitability and spectral tuning by KA channels.(a) Experimental protocol for assessing the effect of blocking KA channels on various physiologically relevant measurements. (b) Schematic of somato-apical trunk showing experimental setup and recording location. (c) Chirp15 stimulus used for assessing intrinsic response dynamics and excitability. Neuron’s voltage response to initial hyperpolarizing test pulse of −100 pA amplitude was used for computing an estimate of input resistance, , whereas the response to Chirp15 stimulus was used to assess intrinsic spectral tuning. (d) Left: Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after blocking KA channels using BaCl2 (orange). Right: V–I plot obtained from the traces shown in left. Input resistance, Rin, was measured as slope of the linear fit to corresponding steady-state V-I curve. (e) Voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange). : temporal summation strength. (f) Voltage traces in response to constant current injection of 100 pA for 700 ms under baseline conditions (blue) and after blocking KA channels (orange). (g) Firing rate profile of the example cell under baseline condition (blue) and after blocking KA channels (orange). (h) Example voltage traces in response to Chirp15 stimulus under baseline condition (blue) and after blocking KA channels (orange). Arrow corresponds to the location of maximal response. (i) Impedance amplitude as a function of input current frequency derived from corresponding color matched traces shown in (h). fR: resonance frequency, Q: resonance strength, /Z/max: maximum impedance amplitude. (j) Impedance phase as a function of input current frequency derived from corresponding color matched traces shown in (h). ΦL: total inductive phase. All traces and measurements depicted in this figure were obtained from the same cell at the soma and recorded at −65 mV.
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f1: Typical experiment demonstrating the regulation of neuronal excitability and spectral tuning by KA channels.(a) Experimental protocol for assessing the effect of blocking KA channels on various physiologically relevant measurements. (b) Schematic of somato-apical trunk showing experimental setup and recording location. (c) Chirp15 stimulus used for assessing intrinsic response dynamics and excitability. Neuron’s voltage response to initial hyperpolarizing test pulse of −100 pA amplitude was used for computing an estimate of input resistance, , whereas the response to Chirp15 stimulus was used to assess intrinsic spectral tuning. (d) Left: Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after blocking KA channels using BaCl2 (orange). Right: V–I plot obtained from the traces shown in left. Input resistance, Rin, was measured as slope of the linear fit to corresponding steady-state V-I curve. (e) Voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange). : temporal summation strength. (f) Voltage traces in response to constant current injection of 100 pA for 700 ms under baseline conditions (blue) and after blocking KA channels (orange). (g) Firing rate profile of the example cell under baseline condition (blue) and after blocking KA channels (orange). (h) Example voltage traces in response to Chirp15 stimulus under baseline condition (blue) and after blocking KA channels (orange). Arrow corresponds to the location of maximal response. (i) Impedance amplitude as a function of input current frequency derived from corresponding color matched traces shown in (h). fR: resonance frequency, Q: resonance strength, /Z/max: maximum impedance amplitude. (j) Impedance phase as a function of input current frequency derived from corresponding color matched traces shown in (h). ΦL: total inductive phase. All traces and measurements depicted in this figure were obtained from the same cell at the soma and recorded 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)

Typical experiment demonstrating the regulation of neuronal excitability and spectral tuning by KA channels.(a) Experimental protocol for assessing the effect of blocking KA channels on various physiologically relevant measurements. (b) Schematic of somato-apical trunk showing experimental setup and recording location. (c) Chirp15 stimulus used for assessing intrinsic response dynamics and excitability. Neuron’s voltage response to initial hyperpolarizing test pulse of −100 pA amplitude was used for computing an estimate of input resistance, , whereas the response to Chirp15 stimulus was used to assess intrinsic spectral tuning. (d) Left: Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after blocking KA channels using BaCl2 (orange). Right: V–I plot obtained from the traces shown in left. Input resistance, Rin, was measured as slope of the linear fit to corresponding steady-state V-I curve. (e) Voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange). : temporal summation strength. (f) Voltage traces in response to constant current injection of 100 pA for 700 ms under baseline conditions (blue) and after blocking KA channels (orange). (g) Firing rate profile of the example cell under baseline condition (blue) and after blocking KA channels (orange). (h) Example voltage traces in response to Chirp15 stimulus under baseline condition (blue) and after blocking KA channels (orange). Arrow corresponds to the location of maximal response. (i) Impedance amplitude as a function of input current frequency derived from corresponding color matched traces shown in (h). fR: resonance frequency, Q: resonance strength, /Z/max: maximum impedance amplitude. (j) Impedance phase as a function of input current frequency derived from corresponding color matched traces shown in (h). ΦL: total inductive phase. All traces and measurements depicted in this figure were obtained from the same cell at the soma and recorded at −65 mV.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Typical experiment demonstrating the regulation of neuronal excitability and spectral tuning by KA channels.(a) Experimental protocol for assessing the effect of blocking KA channels on various physiologically relevant measurements. (b) Schematic of somato-apical trunk showing experimental setup and recording location. (c) Chirp15 stimulus used for assessing intrinsic response dynamics and excitability. Neuron’s voltage response to initial hyperpolarizing test pulse of −100 pA amplitude was used for computing an estimate of input resistance, , whereas the response to Chirp15 stimulus was used to assess intrinsic spectral tuning. (d) Left: Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after blocking KA channels using BaCl2 (orange). Right: V–I plot obtained from the traces shown in left. Input resistance, Rin, was measured as slope of the linear fit to corresponding steady-state V-I curve. (e) Voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after blocking KA channels (orange). : temporal summation strength. (f) Voltage traces in response to constant current injection of 100 pA for 700 ms under baseline conditions (blue) and after blocking KA channels (orange). (g) Firing rate profile of the example cell under baseline condition (blue) and after blocking KA channels (orange). (h) Example voltage traces in response to Chirp15 stimulus under baseline condition (blue) and after blocking KA channels (orange). Arrow corresponds to the location of maximal response. (i) Impedance amplitude as a function of input current frequency derived from corresponding color matched traces shown in (h). fR: resonance frequency, Q: resonance strength, /Z/max: maximum impedance amplitude. (j) Impedance phase as a function of input current frequency derived from corresponding color matched traces shown in (h). ΦL: total inductive phase. All traces and measurements depicted in this figure were obtained from the same cell at the soma and recorded 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