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HCN hyperpolarization-activated cation channels inhibit EPSPs by interactions with M-type K+ channels

Nature Neuroscience volume 12, pages 577584 (2009) | Download Citation

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Abstract

The processing of synaptic potentials by neuronal dendrites depends on both their passive cable properties and active voltage-gated channels, which can generate complex effects as a result of their nonlinear properties. We characterized the actions of HCN (hyperpolarization-activated cyclic nucleotide-gated cation) channels on dendritic processing of subthreshold excitatory postsynaptic potentials (EPSPs) in mouse CA1 hippocampal neurons. The HCN channels generated an excitatory inward current (Ih) that exerted a direct depolarizing effect on the peak voltage of weak EPSPs, but produced a paradoxical hyperpolarizing effect on the peak voltage of stronger, but still subthreshold, EPSPs. Using a combined modeling and experimental approach, we found that the inhibitory action of Ih was caused by its interaction with the delayed-rectifier M-type K+ current. In this manner, Ih can enhance spike firing in response to an EPSP when spike threshold is low and can inhibit firing when spike threshold is high.

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Acknowledgements

We thank J. Dudman for helpful advice and for providing custom data-acquisition routines written in Igor. This work was partially supported by grant MH80745 from the US National Institutes of Health to S.A.S. L.A. and M.S.G. were supported in part by a US National Institutes of Health Director's Pioneer Award, part of the US National Institutes of Health Roadmap for Medical Research, through grant number 5-DP1-OD114-02. M.S.G. was supported in part by Columbia University's Medical Scientist Training Program.

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Affiliations

  1. Department of Neuroscience, Columbia University, New York, New York, USA.

    • Meena S George
    • , L F Abbott
    •  & Steven A Siegelbaum
  2. Departments of Physiology and Cellular Biophysics, Columbia University, New York, New York, USA.

    • L F Abbott
  3. Department of Pharmacology, Columbia University, New York, New York, USA.

    • Steven A Siegelbaum
  4. Howard Hughes Medical Institute, Columbia University, New York, New York, USA.

    • Steven A Siegelbaum

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Contributions

M.S.G. performed all experiments, wrote the computer programs, carried out the analysis and wrote the initial draft of the manuscript. L.F.A. and S.A.S. participated in the design of the experiments and modeling studies and helped in the preparation of the final manuscript.

Corresponding author

Correspondence to Steven A Siegelbaum.

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https://doi.org/10.1038/nn.2307

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