RT Journal Article SR Electronic T1 Fully autonomous mouse behavioral and optogenetic experiments in home-cage JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.12.27.424480 DO 10.1101/2020.12.27.424480 A1 Hao, Yaoyao A1 Thomas, Alyse M. A1 Li, Nuo YR 2020 UL http://biorxiv.org/content/early/2020/12/29/2020.12.27.424480.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.