Fully autonomous mouse behavioral and optogenetic experiments in home-cage

Abstract
Data availability
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Abstract

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

1. Li N
(2021) Autocage version 1.0: Release for Zenodo.
Zenodo, doi:10.5281/zenodo.4716811.

http://www.doi.org/10.5281/zenodo.4716811

Article and author information

Author details

Yaoyao Hao

Baylor College of Medicine, Houston, United States

Competing interests
The authors declare that no competing interests exist.
Alyse Marian Thomas

Baylor College of Medicine, Houston, United States

Competing interests
The authors declare that no competing interests exist.
Nuo Li

Baylor College of Medicine, Houston, United States

For correspondence
nuol@bcm.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6613-5018

Funding

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.

Ethics

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.

Copyright

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.