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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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Fig. 1: Overview of the cell types and geography of the hippocampus.
Fig. 2: Heterogeneity within the CA3 pyramidal cell type.
Fig. 3: Heterogeneity within the CA1 pyramidal cell type.
Fig. 4: Heterogeneity within the subiculum pyramidal cell type.
Fig. 5: Advantages of studying within-cell-type heterogeneity in hippocampal pyramidal cells.

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Acknowledgements

The authors thank E. Bloss and V. Menon for helpful discussions.

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Nature Reviews Neuroscience thanks A. Losonczy, and other anonymous reviewer(s), for their contribution to the peer review of this work.

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M.S.C. researched the data for the article. M.S.C. and N.S. made substantial contributions to the content of the article, wrote the article and reviewed and/or edited the article before submission.

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Glossary

Pattern completion

An operation that allows population activity to converge to a stored pattern despite incomplete or noisy input. In the hippocampus, this operation is classically attributed to CA3 pyramidal cells owing to their recurrent connectivity.

Place fields

The spatial domains in which cells show increased activity, as assayed through in vivo recordings during exploration or navigation.

Sharp wave ripples

Fast oscillations that underlie memory transfer across brain regions during consolidation.

In situ hybridization

(ISH). A histological approach that enables RNA to be labelled in tissue sections.

Next-generation RNA sequencing

A technique that measures whole-genome RNA abundance in a sample via reverse transcription, amplification and sequencing.

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Cembrowski, M.S., Spruston, N. Heterogeneity within classical cell types is the rule: lessons from hippocampal pyramidal neurons. Nat Rev Neurosci 20, 193–204 (2019). https://doi.org/10.1038/s41583-019-0125-5

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