1. Neuroscience
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Fully autonomous mouse behavioral and optogenetic experiments in home-cage

  1. Yaoyao Hao
  2. Alyse Marian Thomas
  3. Nuo Li  Is a corresponding author
  1. Baylor College of Medicine, United States
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Cite this article as: eLife 2021;10:e66112 doi: 10.7554/eLife.66112


Goal-directed behaviors involve distributed brain networks. The small size of the mouse brain makes it amenable to manipulations of neural activity dispersed across brain areas, but existing optogenetic methods serially test a few brain regions at a time, which slows comprehensive mapping of distributed networks. Laborious operant conditioning training required for most experimental paradigms exacerbates this bottleneck. We present an autonomous workflow to survey the involvement of brain regions at scale during operant behaviors in mice. Naïve mice living in a home-cage system learned voluntary head-fixation (>1 hour/day) and performed difficult decision-making tasks, including contingency reversals, for 2 months without human supervision. We incorporated an optogenetic approach to manipulate activity in deep brain regions through intact skull during home-cage behavior. To demonstrate the utility of this approach, we tested dozens of mice in parallel unsupervised optogenetic experiments, revealing multiple regions in cortex, striatum, and superior colliculus involved in tactile decision-making.

Data availability

All hardware design files and software for the construction of automated home-cage system are made available, along with documentations and protocols for automated head-fixation training and task training.<https://github.com/NuoLiLabBCM/Autocage>Source data and code are also available at the same Github repository.

The following data sets were generated

Article and author information

Author details

  1. Yaoyao Hao

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Alyse Marian Thomas

    Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nuo Li

    Baylor College of Medicine, Houston, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6613-5018


Robert and Janice McNair Foundation

  • Nuo Li

McKnight Endowment Fund for Neuroscience

  • Nuo Li

Whitehall Foundation

  • Nuo Li

Alfred P. Sloan Foundation

  • Nuo Li

Searle Scholars Program

  • Nuo Li

Pew Charitable Trusts

  • Nuo Li

National Institutes of Health (NS112312)

  • Nuo Li

National Institutes of Health (NS104781)

  • Nuo Li

National Institutes of Health (NS113110)

  • Nuo Li

Simons Foundation (Simons Collaboration on the Global Brain,543005)

  • Nuo Li

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


Animal experimentation: All procedures were performed in accordance with protocols approved by the Institutional Animal Care and Use Committees at Baylor College of Medicine (protocol AN7012). All surgical procedures were carried out aseptically under 1-2 % isoflurane anesthesia. Buprenorphine Sustained Release (1 mg/kg) and Meloxicam Sustained Release (4mg/kg) were used for pre- and post-operative analgesia.

Reviewing Editor

  1. Brice Bathellier, CNRS, France

Publication history

  1. Received: December 29, 2020
  2. Accepted: May 2, 2021
  3. Accepted Manuscript published: May 4, 2021 (version 1)
  4. Version of Record published: May 12, 2021 (version 2)


© 2021, Hao 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.


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