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

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Systems Neuroscience

Background:

• Goal-directed behaviors rely on complex, distributed brain networks.
• Current methods for mapping these networks in mice are slow due to serial testing and extensive training.
• Optogenetic manipulation of deep brain regions typically requires invasive procedures.

Purpose of the Study:

• To develop an autonomous workflow for large-scale neural circuit mapping during operant behaviors in mice.
• To overcome bottlenecks in traditional experimental paradigms, including training time and serial region testing.
• To enable unsupervised, in-home-cage optogenetic manipulation and behavioral testing.

Main Methods:

• An autonomous home-cage system was established for naive mice.
• Mice learned voluntary head-fixation and performed decision-making tasks for 2 months unsupervised.
• Optogenetic manipulation of deep brain regions was performed through the intact skull during behavior.
• Dozens of mice were tested in parallel unsupervised optogenetic experiments.

Main Results:

• Naive mice successfully learned head-fixation and complex decision-making tasks autonomously.
• The workflow allowed for parallel, unsupervised optogenetic manipulation and behavioral testing.
• Multiple brain regions, including cortex, striatum, and superior colliculus, were identified as involved in tactile decision-making.

Conclusions:

• The developed autonomous workflow significantly accelerates the mapping of distributed neural circuits underlying goal-directed behaviors.
• This approach facilitates large-scale, unsupervised investigation of brain function in mice.
• It reveals novel insights into the neural basis of decision-making and sensory processing.