State-dependent brainstem ensemble dynamics and their interactions with hippocampus across sleep states

  1. Tomomi Tsunematsu
  2. Amisha A Patel
  3. Arno Onken
  4. Shuzo Sakata  Is a corresponding author
  1. University of Strathclyde, United Kingdom
  2. University of Edinburgh, United Kingdom

Abstract

The brainstem plays a crucial role in sleep-wake regulation. However, their ensemble dynamics underlying sleep regulation remain poorly understood. Here we show slow, state-predictive brainstem ensemble dynamics and state-dependent interactions between the brainstem and the hippocampus in mice. On a timescale of seconds to minutes, brainstem populations can predict pupil dilation and vigilance states where they exhibit longer predictable power compared with hippocampal CA1 neurons. On a timescale of sub-seconds, pontine waves (P-waves) are accompanied by synchronous firing of brainstem neurons during both rapid eye movement (REM) and non-REM (NREM) sleep. Crucially, P-waves functionally interact with CA1 activity in a state-dependent manner: during NREM sleep, hippocampal sharp wave-ripples (SWRs) precede P-waves. On the other hand, P-waves during REM sleep are phase-locked with ongoing theta oscillations and are followed by burst firing of CA1 neurons. This state-dependent global coordination between the brainstem and hippocampus implicates distinct functional roles of sleep.

Data availability

The source data files are available online (https://doi.org/10.15129/4f81777a-7b88-48f3-af4d-da484706fa5d).

The following data sets were generated

Article and author information

Author details

  1. Tomomi Tsunematsu

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Amisha A Patel

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Arno Onken

    School of Informatics, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7387-5535
  4. Shuzo Sakata

    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
    For correspondence
    shuzo.sakata@strath.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6796-411X

Funding

Biotechnology and Biological Sciences Research Council (BB/M00905X/1)

  • Shuzo Sakata

Leverhulme Trust (RPG-2015-377)

  • Shuzo Sakata

Alzheimer's Research UK (ARUK-PPG2017B-005)

  • Shuzo Sakata

Action on Hearing Loss (S45)

  • Shuzo Sakata

Engineering and Physical Sciences Research Council (EP/S005692/1)

  • Arno Onken

Japan Society for the Promotion of Science

  • Tomomi Tsunematsu

Uehara Memorial Foundation

  • Tomomi Tsunematsu

Japan Science and Technology Agency (JPMJPR1887)

  • Tomomi Tsunematsu

Japan Society for the Promotion of Science (17H06520)

  • Tomomi Tsunematsu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Laura L Colgin, University of Texas at Austin, United States

Ethics

Animal experimentation: All experimental procedures were performed in accordance with the United Kingdom Animals (Scientific Procedures) Act of 1986 Home Office regulations and approved by the Home Office (PPL 70/8883).

Version history

  1. Received: September 26, 2019
  2. Accepted: January 14, 2020
  3. Accepted Manuscript published: January 14, 2020 (version 1)
  4. Version of Record published: February 3, 2020 (version 2)

Copyright

© 2020, Tsunematsu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,504
    views
  • 607
    downloads
  • 31
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Tomomi Tsunematsu
  2. Amisha A Patel
  3. Arno Onken
  4. Shuzo Sakata
(2020)
State-dependent brainstem ensemble dynamics and their interactions with hippocampus across sleep states
eLife 9:e52244.
https://doi.org/10.7554/eLife.52244

Share this article

https://doi.org/10.7554/eLife.52244

Further reading

    1. Neuroscience
    John J Maurer, Alexandra Lin ... Shinjae Chung
    Research Article

    Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs in mice. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

    1. Neuroscience
    Zilu Liang, Simeng Wu ... Chao Liu
    Research Article

    People form impressions about others during daily social encounters and infer personality traits from others' behaviors. Such trait inference is thought to rely on two universal dimensions: competence and warmth. These two dimensions can be used to construct a ‘social cognitive map’ organizing massive information obtained from social encounters efficiently. Originating from spatial cognition, the neural codes supporting the representation and navigation of spatial cognitive maps have been widely studied. Recent studies suggest similar neural mechanism subserves the map-like architecture in social cognition as well. Here we investigated how spatial codes operate beyond the physical environment and support the representation and navigation of social cognitive map. We designed a social value space defined by two dimensions of competence and warmth. Behaviorally, participants were able to navigate to a learned location from random starting locations in this abstract social space. At the neural level, we identified the representation of distance in the precuneus, fusiform gyrus, and middle occipital gyrus. We also found partial evidence of grid-like representation patterns in the medial prefrontal cortex and entorhinal cortex. Moreover, the intensity of grid-like response scaled with the performance of navigating in social space and social avoidance trait scores. Our findings suggest a neurocognitive mechanism by which social information can be organized into a structured representation, namely cognitive map and its relevance to social well-being.