Abstract
The dendrites of pyramidal neurons have markedly different electrical properties from those of the soma, owing to the non-uniform distribution of voltage-gated ion channels in dendrites. It is thus possible that drugs acting on ion channels might preferentially alter dendritic, but not somatic, excitability. Using dendritic and somatic whole-cell and cell-attached recordings in rat hippocampal slices, we found that the anticonvulsant lamotrigine selectively reduced action potential firing from dendritic depolarization, while minimally affecting firing at the soma. This regional and input-specific effect resulted from an increase in the hyperpolarization-activated cation current (Ih), a voltage-gated current present predominantly in dendrites. These results demonstrate that neuronal excitability can be altered by drugs acting selectively on dendrites, and suggest an important role for Ih in controlling dendritic excitability and epileptogenesis.
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Acknowledgements
We thank R. Gray for writing the data acquisition software and providing help in all phases of experimentation and data analysis. We also thank R. Chitwood, C. Bernard and A. Frick for reading earlier versions of the manuscript. Research was supported by the National Institutes of Health (N.P.P. and D.J.), the National Institute of Deafness and Other Communication Disorders Human Brain Project (M.M.), the National Epifellows Foundation (N.P.P.) and the Hankamer Foundation (D.J.).
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Dr. Poolos has been a member of the GlaxoSmithKline Speaker's Bureau.
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Poolos, N., Migliore, M. & Johnston, D. Pharmacological upregulation of h-channels reduces the excitability of pyramidal neuron dendrites. Nat Neurosci 5, 767–774 (2002). https://doi.org/10.1038/nn891
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DOI: https://doi.org/10.1038/nn891
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