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Research ArticleResearch Article: New Research, Integrative Systems

Parvalbumin Interneurons Are Differentially Connected to Principal Cells in Inhibitory Feedback Microcircuits along the Dorsoventral Axis of the Medial Entorhinal Cortex

Sabine Grosser, Federico J. Barreda, Prateep Beed, Dietmar Schmitz, Sam A. Booker and Imre Vida
eNeuro 2 February 2021, 8 (1) ENEURO.0354-20.2020; https://doi.org/10.1523/ENEURO.0354-20.2020
Sabine Grosser
1Institute for Integrative Neuroanatomy, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany
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Federico J. Barreda
1Institute for Integrative Neuroanatomy, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany
2Bernstein Center for Computational Neuroscience, Berlin 10115, Germany
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Prateep Beed
3Neurowissenschaftliches Forschungszentrum, Charité-Universitätsmedizin, Berlin 10117, Germany
4Berlin Institute of Health, Berlin 10178, Germany
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Dietmar Schmitz
4Berlin Institute of Health, Berlin 10178, Germany
5NeuroCure Cluster of Excellence, Berlin 10117, Germany
6DZNE-German Center for Neurodegenerative Diseases, Berlin 10117, Germany
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Sam A. Booker
1Institute for Integrative Neuroanatomy, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany
7Centre for Discovery Brain Sciences
8Simons Initiative for the Developing Brain
9Patrick Wild Centre for Autism Research, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom
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Imre Vida
1Institute for Integrative Neuroanatomy, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany
5NeuroCure Cluster of Excellence, Berlin 10117, Germany
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Abstract

The medial entorhinal cortex (mEC) shows a high degree of spatial tuning, predominantly grid cell activity, which is reliant on robust, dynamic inhibition provided by local interneurons (INs). In fact, feedback inhibitory microcircuits involving fast-spiking parvalbumin (PV) basket cells (BCs) are believed to contribute dominantly to the emergence of grid cell firing in principal cells (PrCs). However, the strength of PV BC-mediated inhibition onto PrCs is not uniform in this region, but high in the dorsal and weak in the ventral mEC. This is in good correlation with divergent grid field sizes, but the underlying morphologic and physiological mechanisms remain unknown. In this study, we examined PV BCs in layer (L)2/3 of the mEC characterizing their intrinsic physiology, morphology and synaptic connectivity in the juvenile rat. We show that while intrinsic physiology and morphology are broadly similar over the dorsoventral axis, PV BCs form more connections onto local PrCs in the dorsal mEC, independent of target cell type. In turn, the major PrC subtypes, pyramidal cell (PC) and stellate cell (SC), form connections onto PV BCs with lower, but equal probability. These data thus identify inhibitory connectivity as source of the gradient of inhibition, plausibly explaining divergent grid field formation along this dorsoventral axis of the mEC.

  • entorhinal cortex
  • feedback inhibition
  • GABAergic interneurons
  • microcircuit
  • morphology
  • synapse

Footnotes

  • The authors declare no competing financial interests.

  • This work was supported by Deutsche Forschungsgemeinschaft Grants DFG EXC 257 (to D.S. and I.V.) and GRK 1589/2 (to I.V.).

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Parvalbumin Interneurons Are Differentially Connected to Principal Cells in Inhibitory Feedback Microcircuits along the Dorsoventral Axis of the Medial Entorhinal Cortex
Sabine Grosser, Federico J. Barreda, Prateep Beed, Dietmar Schmitz, Sam A. Booker, Imre Vida
eNeuro 2 February 2021, 8 (1) ENEURO.0354-20.2020; DOI: 10.1523/ENEURO.0354-20.2020

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Parvalbumin Interneurons Are Differentially Connected to Principal Cells in Inhibitory Feedback Microcircuits along the Dorsoventral Axis of the Medial Entorhinal Cortex
Sabine Grosser, Federico J. Barreda, Prateep Beed, Dietmar Schmitz, Sam A. Booker, Imre Vida
eNeuro 2 February 2021, 8 (1) ENEURO.0354-20.2020; DOI: 10.1523/ENEURO.0354-20.2020
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Keywords

  • entorhinal cortex
  • feedback inhibition
  • GABAergic interneurons
  • microcircuit
  • morphology
  • synapse

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