h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex
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Abstract
Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single-cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse, supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provide evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.
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- Authors
- Kalmbach, B. E., Buchin, A., Long, B., Close, J., Nandi, A., Miller, J. A., Bakken, T. E., Hodge, R. D., Chong, P., de Frates, R., Dai, K., Maltzer, Z., Nicovich, P. R., Keene, C. D., Silbergeld, D. L., Gwinn, R. P., Cobbs, C., Ko, A. L., Ojemann, J. G., Koch, C., Anastassiou, C. A., Lein, E. S., & Ting, J. T.
- Affiliations
- Allen Institute for Brain Science (US)
- University of Washington (US)
- Swedish Medical Center (US)
- Corresponding author
- Kalmbach, Brian E.
- Ting, Jonathan T.
- ORCID
- Kalmbach, Brian E.
- Buchin, Anatoly
- Long, Brian
- Close, Jennie
- Nandi, Anirban
- Miller, Jeremy A.
- Bakken, Trygve E.
- Hodge, Rebecca D.
- Chong, Peter
- Dai, Kael
- Maltzer, Zoe
- Nicovich, Philip R.
- Keene, C. Dirk
- Silbergeld, Daniel L.
- Gwinn, Ryder P.
- Cobbs, Charles
- Ko, Andrew L.
- Ojemann, Jeffrey G.
- Anastassiou, Costas A.
- Lein, Ed S.
- Ting, Jonathan T.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 100
- Issue
- 5
- Pages
- 1194-1208.e5
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC6447369
- OpenAlex
- W2899419202
- Cited by
- 203
- References
- 84
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 31 · 2023: 45 · 2022: 28 · 2021: 27 · 2020: 21 · 2019: 9
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (U01MH114812)
- Chan Zuckerberg Initiative (2017-174399)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hyperpolarization-activated cation channels, HCN1, cerebral cortex, cortical depth, membrane properties, theta oscillations, excitatory neurons, single-cell RNA sequencing
- MeSH terms
- Adult, Animals, Cell Membrane, Cerebral Cortex, Female, Humans, Male, Membrane Potentials, Mice, Inbred C57BL, Mice, Transgenic, Models, Neurological, Species Specificity, Potassium Channels, Pyramidal Cells, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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