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Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples

Kajikawa, Koichiro and Hulse, Brad K. and Siapas, Athanassios G. and Lubenov, Evgueniy V. (2021) Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples. . (Unpublished)

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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.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Hulse, Brad K.0000-0002-7117-7036
Siapas, Athanassios G.0000-0001-8837-678X
Lubenov, Evgueniy V.0000-0002-1099-944X
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. Posted April 22, 2021. We thank Lee-Peng Mok for help with histological processing and immunohistochemistry, Maria Papadopoulou and Stijn Cassenear for help with imaging, insightful discussions and feedback on the manuscript, and Kevin Shan for help with the data processing pipeline and insightful discussion. Confocal imaging was performed at the Caltech Biological Imaging Facility. This work was supported by a Vannevar Bush Faculty Fellowship, the Mathers Foundation, the McKnight Foundation, and NIH grant RO1MH113016. Author Contributions: AGS, EVL, BKH, KK designed the experiments. KK, BKH performed the experiments. EVL led the analysis in collaboration with KK, AGS, BKH. EVL, AGS, KK wrote the paper with input from BKH. The authors have declared no competing interest.
Funding AgencyGrant Number
Vannevar Bush FellowshipUNSPECIFIED
Mathers FoundationUNSPECIFIED
McKnight FoundationUNSPECIFIED
Record Number:CaltechAUTHORS:20210422-132142278
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Official Citation: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:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108806
Deposited By: Tony Diaz
Deposited On:23 Apr 2021 16:45
Last Modified:16 Nov 2021 19:32

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