Automated home cage training of mice in a hold-still center-out reach task

Abstract

An obstacle to understanding neural mechanisms of movement is the complex, distributed nature of the mammalian motor system. Here we present a novel behavioral paradigm for high-throughput dissection of neural circuits underlying mouse forelimb control. Custom touch-sensing joysticks were used to quantify mouse forelimb trajectories with micron-millisecond spatiotemporal resolution. Joysticks were integrated into computer-controlled, rack-mountable home cages, enabling batches of mice to be trained in parallel. Closed loop behavioral analysis enabled online control of reward delivery for automated training. We used this system to show that mice can learn, with no human handling, a direction-specific hold-still center-out reach task in which a mouse first held its right forepaw still before reaching out to learned spatial targets. Stabilogram diffusion analysis of submillimeter-scale micromovements produced during the hold demonstrate that an active control process, akin to upright balance, was implemented to maintain forepaw stability. Trajectory decomposition methods, previously used in primates, were used to segment hundreds of thousands of forelimb trajectories into millions of constituent kinematic primitives. This system enables rapid dissection of neural circuits for controlling motion primitives from which forelimb sequences are built. NEW & NOTEWORTHY A novel joystick design resolves mouse forelimb kinematics with micron-millisecond precision. Home cage training is used to train mice in a hold-still center-out reach task. Analytical methods, previously used in primates, are used to decompose mouse forelimb trajectories into kinematic primitives.

A distributed neocortical action map associated with reach-to-grasp

“…Within the context of motor control, our findings also encourage to study the role of areas found to be active during movement (such as the visual areas) commonly disregarded in the association to forelimb movement, at the cellular-level (Galiñanes et al, 2018, Karandell and Huber, 2017, Ebina et al, 2018). In the future, it would also be relevant to assess the neocortical dynamics during RtG in a freely moving condition or during performance refinement, considering that cortical areas undergo functional reorganization during learning (Makino et al, 2017; Whishaw et al, 2017; Bollu et al, 2019; Hwang et al, 2019). In sum, our investigation identified a global network of neocortical area associated to successful RtG execution.…”

“…Within the context of motor control, our findings also encourage to study the role of areas found to be active during movement (such as the visual areas) commonly disregarded in the association to forelimb movement, at the cellular-level (Galianes et al, 2018, Karandell and Huber, 2017, Ebina et al, 2018). In the future, it would also be relevant to assess the neocortical dynamics during RtG in a freely moving condition or during performance refinement (Makino et al, 2017; Whishaw et al, 2017; Bollu et al, 2019). In sum, our investigation identified a global network of neocortical areas beyond those previously known to be associated with goal-directed arm movements and suggest that the operating mode of the mouse neocortex underlying unilateral goal-directed movements involves distant communication across bothhemispheres, while encoding of movement parameters occurs locally, and, in the context of our investigations, mostly in the secondary motor areas.…”

Open-Source Joystick Manipulandum for Decision-Making, Reaching, and Motor Control Studies in Mice

“…Perhaps of most use, the described tool setup be used in automated training, thus enabling high-throughput research methods, a critical avenue for the future of neuroscience. While one may glean how to build joystick rigs from other sources (Bollu et al, 2019), we provide the first documentation of a selfcentering joystick with extensive online task code and offline analysis.…”

“…With one coil removed, it takes only 0.18 N to displace the joystick 1 cm. Other solutions include using a near zero resistance joystick designed for rodents, particularly that described in Bollu et al (2019).…”

“…This goal-oriented movement is highly quantifiable, reproducible, and unitary, unlike other tasks common to rodents that require several actions, such as reorientation followed by locomotion across a cage (Tai et al, 2012;Lak et al, 2014). Despite its simplicity, the action provides rich spatiotemporal dynamics (Bollu et al, 2019) that do not exist in other paradigms such as lever presses. The quantification of such richness is made trivial through the use of joysticks.…”