Heterogeneity within classical cell types is the rule: lessons from hippocampal pyramidal neurons
Abstract
The mechanistic operation of brain regions is often interpreted by partitioning constituent neurons into 'cell types'. Historically, such cell types were broadly defined by their correspondence to gross features of the nervous system (such as cytoarchitecture). Modern-day neuroscientific techniques, enabling a more nuanced examination of neuronal properties, have illustrated a wealth of heterogeneity within these classical cell types. Here, we review the extent of this within-cell-type heterogeneity in one of the simplest cortical regions of the mammalian brain, the rodent hippocampus. We focus on the mounting evidence that the classical CA3, CA1 and subiculum pyramidal cell types all exhibit prominent and spatially patterned within-cell-type heterogeneity, and suggest these cell types provide a model system for exploring the organization and function of such heterogeneity. Given that the hippocampus is structurally simple and evolutionarily ancient, within-cell-type heterogeneity is likely to be a general and crucial feature of the mammalian brain.
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CA1 pyramidal neurons show a high level of heterogeneity at the molecular, cellular, connectivity, and in-vivo properties.
“CA1 pyramidal neurons show a high level of heterogeneity at the molecular, cellular, connectivity, and in-vivo properties90–92.”
From Place and behavioral modulation of hippocampal neurons during immobility (2026) · cites this paper as [91]
CA1, CA3 and SUB have gradual gene expression and connectivity changes along multiple dimensions - superficial-deep, proximal-distal and dorsal-ventral.
“CA1, CA3 and SUB have gradual gene expression and connectivity changes along multiple dimensions – superficial-deep, proximal-distal and dorsal-ventral (Cembrowski and Spruston, 2019).”
From A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation (2021) · cites this paper as Cembrowski and Spruston, 2019
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A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation
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“Electrophysiological, biochemical, immunohistochemical, and genetic methods have subsequently helped define and distinguish increasingly more specific sets of neurons (reviewed recently in (Klausberger and Somogyi, 2008; Huang and Paul, 2019; Tremblay et al., 2016; Zeng and Sanes, 2017; Cembrowski and Spruston, 2019)).”
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Circuit and molecular architecture of a ventral hippocampal network
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“…Maruoka et al., 2017; Saunders et al., 2018; Strange et al., 2014; Tasic et al., 2018), although there is likely greater flexibility in the wiring of mammalian circuits and greater heterogeneity within cell types in the mammalian brain (Cembrowski and Menon, 2018; Cembrowski and Spruston, 2019).”
Backgroundsc2GWAS: a comprehensive platform linking single cell and GWAS traits of human
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Place and behavioral modulation of hippocampal neurons during immobility
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- Authors
- Cembrowski, M. S., & Spruston, N.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Nature Reviews Neuroscience
- Published
- 2019-02-18
- Volume
- 20
- Issue
- 4
- Pages
- 193-204
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2914346278
- Cited by
- 258
- References
- 168
- Citations by year
- 2026: 34 · 2025: 42 · 2024: 39 · 2023: 29 · 2022: 38 · 2021: 35 · 2020: 32 · 2019: 8
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- neuronal heterogeneity, hippocampal pyramidal neurons, cell types, CA3, CA1, subiculum, hippocampus, cortical organization, mammalian brain evolution
- MeSH terms
- Action Potentials, Animals, Hippocampus, Pyramidal Cells
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