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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 suprathreshold intrinsic excitability across the somato-apical trunk.(a) Same as Fig. 2a. (b) Voltage traces recorded from dendrites located at 240 μm (top; 200 pA current) and 270 μm (bottom; 250 pA current) away from the soma under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) and 3,4-DAP (bottom), respectively. Note that action potentials fired in bursts riding on a plateau after blocking KA channels. (c–e) Population plots of action potential firing frequency as a function of injected current amplitude at soma (c), dendrites around 125 μm (d) and dendrites around 250 μm (e) before (open circles) and after (filled circles) blocking KA channels using BaCl2 (top) or 3,4-DAP (bottom). *p < 0.05, **p < 0.005, ***p < 0.0005, paired Student’s t test. Data is presented as mean ± SEM. All measurements were obtained at −65 mV.
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f3: Blocking KA channels resulted in increased suprathreshold intrinsic excitability across the somato-apical trunk.(a) Same as Fig. 2a. (b) Voltage traces recorded from dendrites located at 240 μm (top; 200 pA current) and 270 μm (bottom; 250 pA current) away from the soma under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) and 3,4-DAP (bottom), respectively. Note that action potentials fired in bursts riding on a plateau after blocking KA channels. (c–e) Population plots of action potential firing frequency as a function of injected current amplitude at soma (c), dendrites around 125 μm (d) and dendrites around 250 μm (e) before (open circles) and after (filled circles) blocking KA channels using BaCl2 (top) or 3,4-DAP (bottom). *p < 0.05, **p < 0.005, ***p < 0.0005, paired Student’s t test. Data is presented as mean ± SEM. All measurements were obtained at −65 mV.

Mentions: Turning to suprathreshold measures of excitability, we found that blocking KA channels significantly increased the firing frequency at various locations along the somato-dendritic axis (Fig. 3). With blockade of KA channels using either blocker, at higher current injections the pattern of action potential firing transitioned to burst firing in somatic recordings, whereas dendritic recordings showed an enhanced presence of plateau potentials24 (Fig. 3b). Specifically, after bath application of 3,4-DAP, 19 out of 21 recordings across the somato-apical axis showed robust burst firing with plateau potentials (soma: 7/7; ~125 μm: 7/7; ~250 μm: 5/7). On the other hand, bath application of BaCl2 was less efficient in inducing burst firing with plateau potentials, with only 8 out of 18 recordings made across the somato-apical axis displaying bursting with plateau potentials (soma: 0/6; ~125 μm: 4/6; ~250 μm: 4/6). Additionally, in a small percentage of recordings, the neuron switched to spontaneous firing after blocking KA channels (5/20 for BaCl2 and 9/28 for 3,4-DAP). Taken together, our results show that blocking KA channels results in significantly enhanced sub- and supra-threshold somatodendritic intrinsic excitability.


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 suprathreshold intrinsic excitability across the somato-apical trunk.(a) Same as Fig. 2a. (b) Voltage traces recorded from dendrites located at 240 μm (top; 200 pA current) and 270 μm (bottom; 250 pA current) away from the soma under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) and 3,4-DAP (bottom), respectively. Note that action potentials fired in bursts riding on a plateau after blocking KA channels. (c–e) Population plots of action potential firing frequency as a function of injected current amplitude at soma (c), dendrites around 125 μm (d) and dendrites around 250 μm (e) before (open circles) and after (filled circles) blocking KA channels using BaCl2 (top) or 3,4-DAP (bottom). *p < 0.05, **p < 0.005, ***p < 0.0005, paired Student’s t test. Data is presented as 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

f3: Blocking KA channels resulted in increased suprathreshold intrinsic excitability across the somato-apical trunk.(a) Same as Fig. 2a. (b) Voltage traces recorded from dendrites located at 240 μm (top; 200 pA current) and 270 μm (bottom; 250 pA current) away from the soma under baseline condition (blue) and after blocking KA channels (orange) using BaCl2 (top) and 3,4-DAP (bottom), respectively. Note that action potentials fired in bursts riding on a plateau after blocking KA channels. (c–e) Population plots of action potential firing frequency as a function of injected current amplitude at soma (c), dendrites around 125 μm (d) and dendrites around 250 μm (e) before (open circles) and after (filled circles) blocking KA channels using BaCl2 (top) or 3,4-DAP (bottom). *p < 0.05, **p < 0.005, ***p < 0.0005, paired Student’s t test. Data is presented as mean ± SEM. All measurements were obtained at −65 mV.
Mentions: Turning to suprathreshold measures of excitability, we found that blocking KA channels significantly increased the firing frequency at various locations along the somato-dendritic axis (Fig. 3). With blockade of KA channels using either blocker, at higher current injections the pattern of action potential firing transitioned to burst firing in somatic recordings, whereas dendritic recordings showed an enhanced presence of plateau potentials24 (Fig. 3b). Specifically, after bath application of 3,4-DAP, 19 out of 21 recordings across the somato-apical axis showed robust burst firing with plateau potentials (soma: 7/7; ~125 μm: 7/7; ~250 μm: 5/7). On the other hand, bath application of BaCl2 was less efficient in inducing burst firing with plateau potentials, with only 8 out of 18 recordings made across the somato-apical axis displaying bursting with plateau potentials (soma: 0/6; ~125 μm: 4/6; ~250 μm: 4/6). Additionally, in a small percentage of recordings, the neuron switched to spontaneous firing after blocking KA channels (5/20 for BaCl2 and 9/28 for 3,4-DAP). Taken together, our results show that blocking KA channels results in significantly enhanced sub- and supra-threshold somatodendritic intrinsic excitability.

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