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. Naive mice living in a home-cage system learned voluntary head-fixation (>1 hr/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.
Highlights
Goal-directed behavior is orchestrated by activity distributed across multiple brain regions
Our goal is to develop an automated workflow to swiftly probe the involvement of many brain regions in a single perceptual decision task
We designed a robust home-cage system for mice to voluntarily engage in head-fixation that was amenable to operant conditioning and optogenetic testing (Figure 1C)
Summary
Goal-directed behavior is orchestrated by activity distributed across multiple brain regions. Delineating which activity casually contributes to decision-making requires spatially and temporally precise manipulation of specific activity that is widely dispersed across the brain. Modern optogenetic methods can manipulate activity in specific brain regions with excellent temporal resolution (Deisseroth, 2015; Wiegert et al, 2017; Li et al, 2019), but optogenetic experiments currently can only probe a limited number of brain regions in single studies. Mice are trained in operant behavior and optogenetic testing is carried out in daily sessions to manipulate individual brain regions. This process is serial and slow, prohibiting comprehensive surveys of many brain regions during complex behaviors
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