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Parvalbumin interneurons provide grid cell–driven recurrent inhibition in the medial entorhinal cortex

Nature Neuroscience volume 17, pages 710–718 (2014)Cite this article

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Abstract

Grid cells in the medial entorhinal cortex (MEC) generate metric spatial representations. Recent attractor-network models suggest an essential role for GABAergic interneurons in the emergence of the grid-cell firing pattern through recurrent inhibition dependent on grid-cell phase. To test this hypothesis, we studied identified parvalbumin-expressing (PV+) interneurons that are the most likely candidate for providing this recurrent inhibition onto grid cells. Using optogenetics and tetrode recordings in mice, we found that PV+ interneurons exhibited high firing rates, low spatial sparsity and no spatial periodicity. PV+ interneurons inhibited all functionally defined cell types in the MEC and were in turn recruited preferentially by grid cells. To our surprise, we found that individual PV+ interneurons received input from grid cells with various phases, which most likely accounts for the broadly tuned spatial firing activity of PV+ interneurons. Our data argue against the notion that PV+ interneurons provide phase-dependent recurrent inhibition and challenge recent attractor-network models of grid cells.

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Figure 1: Cell type–specific expression of ChR2-mCherry in PV+ interneurons of the MEC.
Figure 2: Identification of PV+ interneurons in PV-Cre mice.
Figure 3: Firing characteristics of PV+ interneurons.
Figure 4: Absence of grid-cell pattern in the firing of PV+ interneurons.
Figure 5: Inhibition of spatially selective cells by PV+ interneurons.
Figure 6: Theta phase–specific stimulation of PV+ interneurons inhibits MEC neurons without affecting their spatial selectivity.
Figure 7: Connectivity between excitatory cells and PV+ interneurons.

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Acknowledgements

We thank E. Savenkova and U. Amtmann for their technical assistance, W. Kelsch for providing help at initial stages of the study, M. Michael for immunohistochemical work, and P. Latuske for help with pilot experiments. This work was supported by a Humboldt Research Fellowship for Postdoctoral Studies and a grant from the Innovation Fund FRONTIER of Heidelberg University to K.A., a grant from the European Research Council Advanced Grant (Proposal number 250047) to H.M., and a grant from the German Ministry for Education and Research (BMBF, 01GQ1003A).

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  1. Department of Clinical Neurobiology at the Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Christina Buetfering, Kevin Allen & Hannah Monyer

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  1. Christina Buetfering
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C.B., K.A. and H.M. designed the experiments and wrote the manuscript. C.B. and K.A. performed in vivo electrophysiological experiments. C.B and K.A. analyzed the data.

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Correspondence to Hannah Monyer.

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Buetfering, C., Allen, K. & Monyer, H. Parvalbumin interneurons provide grid cell–driven recurrent inhibition in the medial entorhinal cortex. Nat Neurosci 17, 710–718 (2014). https://doi.org/10.1038/nn.3696

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