Fully autonomous mouse behavioral and optogenetic experiments in home-cage.
Fully autonomous mouse behavioral and optogenetic experiments in home-cage.
复制标题
作者：
Hao Y;Thomas AM;Li N
目标导向的行为涉及分布式大脑网络。小鼠大脑体积较小，适合对分散在大脑区域的神经活动进行操纵，但现有的光遗传学方法一次连续测试几个大脑区域，这减慢了分布式网络的综合映射。大多数实验范式所需的艰苦的操作性条件训练加剧了这一瓶颈。我们提出了一个自主工作流程来大规模调查小鼠操作行为期间大脑区域的参与情况。生活在家庭笼子系统中的幼鼠在没有人类监督的情况下学习了自愿头部固定（> 1小时/天）并执行困难的决策任务，包括应急逆转，持续两个月。我们采用光遗传学方法，在家庭笼养行为期间通过完整的头骨操纵深部大脑区域的活动。为了证明这种方法的实用性，我们在平行的无监督光遗传学实验中测试了数十只小鼠，揭示了皮层、纹状体和上丘中参与触觉决策的多个区域。
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.