Cell types for our sense of location: where we are and where we are going

Abstract

Technological advances in profiling cells along genetic, anatomical and physiological axes have fomented interest in identifying all neuronal cell types. This goal nears completion in specialized circuits such as the retina, while remaining more elusive in higher order cortical regions. We propose that this differential success of cell type identification may not simply reflect technological gaps in co-registering genetic, anatomical and physiological features in the cortex. Rather, we hypothesize it reflects evolutionarily driven differences in the computational principles governing specialized circuits versus more general-purpose learning machines. In this framework, we consider the question of cell types in medial entorhinal cortex (MEC), a region likely to be involved in memory and navigation. While MEC contains subsets of identifiable functionally defined cell types, recent work employing unbiased statistical methods and more diverse tasks reveals unsuspected heterogeneity and adaptivity in MEC firing patterns. This suggests MEC may operate more as a generalist circuit, obeying computational design principles resembling those governing other higher cortical regions.

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Figure 1: The range at which clear cell type clustering emerges varies across neural circuits.
Figure 2: Capturing coding in MEC using a tuning-curve score versus model-based method.
Figure 3: Entorhinal neurons represent multiple task variables in heterogeneous ways.

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Acknowledgements

L.M.G. is a New York Stem Cell Foundation – Robertson Investigator. This work was supported by funding from The New York Stem Cell Foundation, the James S. McDonnell Foundation, NIMH MH106475 and a Klingenstein-Simons Fellowship to L.M.G.; the Bio-X Interdisciplinary Initiatives Program and a Simons Foundation grant to L.M.G. and S.G.; and the Burroughs-Wellcome, the Alfred P. Sloan Foundation, the McKnight Foundation, the James S. McDonnell Foundation and an Office of Naval Research grant to S.G., as well as an NSF-IGERT from the Stanford MBC Program and a Stanford Interdisciplinary Graduate Fellowship to K.H.

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Correspondence to Surya Ganguli or Lisa M Giocomo.

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Hardcastle, K., Ganguli, S. & Giocomo, L. Cell types for our sense of location: where we are and where we are going. Nat Neurosci 20, 1474–1482 (2017). https://doi.org/10.1038/nn.4654

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