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Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples

Koichiro Kajikawa, View ORCID ProfileBrad K. Hulse, View ORCID ProfileAthanassios G. Siapas, View ORCID ProfileEvgueniy V. Lubenov
doi: https://doi.org/10.1101/2021.04.20.440699
Koichiro Kajikawa
1Division of Biology and Biological Engineering, Division of Engineering and Applied Science, Computation and Neural Systems Program, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA
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Brad K. Hulse
1Division of Biology and Biological Engineering, Division of Engineering and Applied Science, Computation and Neural Systems Program, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA
2Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
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Athanassios G. Siapas
1Division of Biology and Biological Engineering, Division of Engineering and Applied Science, Computation and Neural Systems Program, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA
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  • For correspondence: lubenov@caltech.edu thanos@caltech.edu
Evgueniy V. Lubenov
1Division of Biology and Biological Engineering, Division of Engineering and Applied Science, Computation and Neural Systems Program, California Institute of Technology, 1200 East California Blvd., Pasadena, CA 91125, USA
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  • For correspondence: lubenov@caltech.edu thanos@caltech.edu
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ABSTRACT

Hippocampal ripples are transient population bursts that structure cortico-hippocampal communication and play a central role in memory processing. However, the mechanisms controlling ripple initiation in behaving animals remain poorly understood. Here we combine multisite extracellular and whole cell recordings in awake mice to contrast the brain state and ripple modulation of subthreshold dynamics across hippocampal subfields. We find that entorhinal input to DG exhibits UP and DOWN dynamics with ripples occurring exclusively in UP states. While elevated cortical input in UP states generates depolarization in DG and CA1, it produces persistent hyperpolarization in CA3 neurons. Furthermore, growing inhibition is evident in CA3 throughout the course of the ripple buildup, while DG and CA1 neurons exhibit depolarization transients 100 ms before and during ripples. These observations highlight the importance of CA3 inhibition for ripple generation, while pre-ripple responses indicate a long and orchestrated ripple initiation process in the awake state.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 22, 2021.
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Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples
Koichiro Kajikawa, Brad K. Hulse, Athanassios G. Siapas, Evgueniy V. Lubenov
bioRxiv 2021.04.20.440699; doi: https://doi.org/10.1101/2021.04.20.440699
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Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples
Koichiro Kajikawa, Brad K. Hulse, Athanassios G. Siapas, Evgueniy V. Lubenov
bioRxiv 2021.04.20.440699; doi: https://doi.org/10.1101/2021.04.20.440699

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