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Brain State Dependence of Hippocampal Subthreshold Activity in Awake Mice

Hulse, Brad K. and Lubenov, Evgueniy V. and Siapas, Athanassios G. (2017) Brain State Dependence of Hippocampal Subthreshold Activity in Awake Mice. Cell Reports, 18 (1). pp. 136-147. ISSN 2211-1247. PMCID PMC5217705. doi:10.1016/j.celrep.2016.11.084.

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Monitoring the membrane potential of individual neurons has uncovered how single-cell properties contribute to network processing across different brain states in neocortex. In contrast, the subthreshold modulation of hippocampal neurons by brain state has not been systematically characterized. To address this, we combined whole-cell recordings from dentate granule cells and CA1 pyramidal neurons with multisite extracellular recordings and behavioral measurements in awake mice. We show that the average membrane potential, amplitude of subthreshold fluctuations, and distance to spike threshold are all modulated by brain state. Furthermore, even within individual states, rapid variations in arousal are reflected in membrane potential fluctuations. These factors produce depolarizing ramps in the membrane potential of hippocampal neurons that precede ripples and mirror transitions to a network regime conducive for ripple generation. These results suggest that there are coordinated shifts in the subthreshold dynamics of individual neurons that underlie the transitions between distinct modes of hippocampal processing.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Hulse, Brad K.0000-0002-7117-7036
Lubenov, Evgueniy V.0000-0002-1099-944X
Siapas, Athanassios G.0000-0001-8837-678X
Additional Information:© 2017 The Author(s). This is an open access article under the CC BY-NC-ND license ( Received 26 July 2016, Revised 7 November 2016, Accepted 30 November 2016, Available online 3 January 2017. We thank Stijn Cassenaer, Koichiro Kajikawa, Maria Papadopoulou, Britton Sauerbrei, and Kevin Shan for helpful discussion and comments on the manuscript; Andreas Hoenselaar and Mike Walsh for help with instrumentation; Lee-Peng Mok for help with immunohistochemistry; and Koichiro Kajikawa for help with dentate experiments. Confocal imaging was performed in the Caltech Biological Imaging Facility with the support of the Caltech Beckman Institute and the Beckman Foundations. This work was supported by the Mathers Foundation, the Moore Foundation, NIH grant 1DP1OD008255/5DP1MH099907, NSF grant IOS-1146871, and the iARPA contract D16PC00003.
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
Mathers FoundationUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
Intelligence Advanced Research Projects Activity (iARPA)D16PC00003
Subject Keywords:brain state; hippocampus; ripples; sharp waves; large irregular activity; small irregular activity; theta; neuromodulation; arousal; membrane potential
Issue or Number:1
PubMed Central ID:PMC5217705
Record Number:CaltechAUTHORS:20170109-101217178
Persistent URL:
Official Citation:Brad K. Hulse, Evgueniy V. Lubenov, Athanassios G. Siapas, Brain State Dependence of Hippocampal Subthreshold Activity in Awake Mice, Cell Reports, Volume 18, Issue 1, 3 January 2017, Pages 136-147, ISSN 2211-1247, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73331
Deposited By: Tony Diaz
Deposited On:09 Jan 2017 21:05
Last Modified:06 Apr 2022 19:32

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