A Highly-Scalable Automated Rodent Training Platform

Journal of Neuroscience Methods, 2021

Background: Training non-human primates (NHPs) for translational medical experimentation is an essential yet time consuming process. To increase training efficiency, some training systems have been designed for NHPs to use at their home cages. Several autonomous cage-side tablet-based systems have been proposed, but none of these systems allow for remote monitoring and task modification while also being wireless, low-cost, light weight, and portable. New method: Here we present ACTS: an Autonomous Cage-side Training System which meets all these criteria. ACTS consists of 1) a touchscreen tablet and a speaker attached to the subject's home cage, 2) an inexpensive reward system made from a slightly modified fish feeder, and 3), a laptop operating the system wirelessly and remotely via a router. Results: We were able to test the system and wirelessly train two macaques in their home cages. Remote access enabled us to control ACTS from up to 90 m, through up to 3 walls, and through a floor of a building. The device is compatible with different reward pellet sizes and could run about two hours with a ~4 mm pellet size. The animals were able to generalize the task when transferred to a traditional experimental rig. Comparison with existing methods: The low cost and modest skill required to build and implement ACTS lowers the barrier for NHP researchers and caregivers to deploy autonomous, remotely controlled tablet-based cage-side systems. Conclusion: ACTS can be used for low-cost, wireless cage-side training of NHPs being prepared for translational medical experimentation.

Behavior Research Methods, 2014

The increasing demand for highly automated and flexible tasks capable of assessing visual learning and memory in nonhuman animals has led to the exciting development of a wide array of prefabricated touchscreen-equipped systems. However, the high cost of these prefabricated systems has led many researchers to develop or modify their own preexisting equipment. We developed a freely downloadable App, the Touchscreeen Behavioral Evaluation System (TBES) for use in conjunction with an iPad (Apple, Cupertino, California) as an alternative to prefabricated touchscreen systems. TBES allows for stimulus presentation and data collection on an iPad. The touchscreen technology offered by the iPad is attractive to researchers due to its affordability, reliability, and resistance to false inputs. We highlight these, as well as the feasibility and procedural flexibility of TBES, in an effort to promote our system as a competitive alternative to those currently available.

2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2012

Inexpensive, high-throughput, low maintenance systems for precise temporal and spatial measurement of mouse home cage behavior (including movement, feeding, and drinking) are required to evaluate products from large scale pharmaceutical design and genetic lesion programs. These measurements are also required to interpret results from more focused behavioral assays. We describe the design and validation of a highly-scalable, reliable mouse home cage behavioral monitoring system modeled on a previously described, one-ofa-kind system [1]. Mouse position was determined by solving static equilibrium equations describing the force and torques acting on the system strain gauges; feeding events were detected by a photobeam across the food hopper, and drinking events were detected by a capacitive lick sensor. Validation studies show excellent agreement between mouse position and drinking events measured by the system compared with video-based observation-a gold standard in neuroscience.

eLife, 2021

Feeding is critical for survival, and disruption in the mechanisms that govern food intake underlies disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation in rodent home-cages: the Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs.

PeerJ, 2017

We created an easy-to-use device for operant licking experiments and another device that records environmental variables. Both devices use the Raspberry Pi computer to obtain data from multiple input devices (e.g., radio frequency identification tag readers, touch and motion sensors, environmental sensors) and activate output devices (e.g., LED lights, syringe pumps) as needed. Data gathered from these devices are stored locally on the computer but can be automatically transferred to a remote server via a wireless network. We tested the operant device by training rats to obtain either sucrose or water under the control of a fixed ratio, a variable ratio, or a progressive ratio reinforcement schedule. The lick data demonstrated that the device has sufficient precision and time resolution to record the fast licking behavior of rats. Data from the environment monitoring device also showed reliable measurements. By providing the source code and 3D design under an open source license, we...

Frontiers in behavioral neuroscience, 2018

High-throughput behavioral training of rodents has been a transformative development for systems neuroscience. Water or food restriction is typically required to motivate task engagement. We hypothesized a gap between physiological water need and hedonic water satiety that could be leveraged to train rats for water rewards without water restriction. We show that when Citric Acid (CA) is added to water, female rats drink less, yet consume enough to maintain long term health. With 24 h/day access to a visual task with water rewards, rats with CA water performed 84% ± 18% as many trials as in the same task under water restriction. In 2-h daily sessions, rats with CA water performed 68% ± 13% as many trials as under water restriction. Using reward sizes <25 μl, rats with CA performed 804 ± 285 trials/day in live-in sessions or 364 ± 82 trials/day in limited duration daily sessions. The safety of CA water amendment was previously shown for male rats, and the gap between water need and...

Scientific Reports

In neurophysiology, nonhuman primates represent an important model for studying the brain. Typically, monkeys are moved from their home cage to an experimental room daily, where they sit in a primate chair and interact with electronic devices. Refining this procedure would make the researchers’ work easier and improve the animals’ welfare. To address this issue, we used home-cage training to train two macaque monkeys in a non-match-to-goal task, where each trial required a switch from the choice made in the previous trial to obtain a reward. The monkeys were tested in two versions of the task, one in which they acted as the agent in every trial and one in which some trials were completed by a “ghost agent”. We evaluated their involvement in terms of their performance and their interaction with the apparatus. Both monkeys were able to maintain a constant involvement in the task with good, stable performance within sessions in both versions of the task. Our study confirms the feasibil...

Behavioral biology, 1974

Three experiments were carried out to study improvement of performance with time on appetitive tasks in BALB/c mice. Experiments 1 and 2 showed that a 24-hr interval between learning sessions significantly improves performance. It seems that there was a curvilinear relationship between this improvement and the 1st learning session duration.

Animals, 2020

A conditioned reinforcer is a stimulus that acquired its effectiveness to increase and maintain a target behavior on the basis of the individual’s history—e.g., pairings with other reinforcers. This systematic review synthesized findings on conditioned reinforcement in the applied animal training field. Thirty-four studies were included in the review and six studies were eligible for a meta-analysis on the effectiveness of behavioral interventions that implemented conditioned reinforcement (e.g., clicks, spoken word, or whistles paired with food). The majority of studies investigated conditioned reinforcement with dogs (47%, n = 16) and horses (30%, n = 10) implementing click–food pairings. All other species (cats, cattle, fish, goats, and monkeys) were equally distributed across types of conditioned (e.g., clicker or spoken word) and unconditioned reinforcers (e.g., food, water, or tactile). A meta-analysis on the effectiveness of conditioned reinforcement in behavioral interventio...

Frontiers in neural circuits, 2018

Understanding neuronal mechanisms of learned behaviors requires efficient behavioral assays. We designed a high-throughput automatic training system (HATS) for olfactory behaviors in head-fixed mice. The hardware and software were constructed to enable automatic training with minimal human intervention. The integrated system was composed of customized 3D-printing supporting components, an odor-delivery unit with fast response, Arduino based hardware-controlling and data-acquisition unit. Furthermore, the customized software was designed to enable automatic training in all training phases, including lick-teaching, shaping and learning. Using HATS, we trained mice to perform delayed non-match to sample (DNMS), delayed paired association (DPA), Go/No-go (GNG), and GNG reversal tasks. These tasks probed cognitive functions including sensory discrimination, working memory, decision making and cognitive flexibility. Mice reached stable levels of performance within several days in the task...

2004

The Psikharpax project aims at endowing a robot with a sensori-motor equipment and a neural control architecture that will afford some of the capacities of autonomy and adaptation that are exhibited by real rats. The paper summarizes the current state of achievement of the project. It successively describes the robot's future sensors and actuators, and several biomimetic models of the anatomy and physiology of structures in the rat's brain, like the hippocampus and the basal ganglia, that have already been put at work on various robots and that make navigation and action selection possible. Preliminary results on the implementation of learning mechanisms in these structures are also presented.

Journal of The Experimental Analysis of Behavior, 1996

We describe an operant conditioning apparatus that uses computerized touch-screen technology and is designed for the versatile and highly controlled testing of rats in a potentially wide variety of behavioral paradigms. Although computer-controlled touch-screen systems have been developed for use with pigeons, monkeys, and humans, analogous technologies and methods have not yet been developed for rats. The development of a touch-screen system for rats could enhance the efficiency of behavioral research with rats, and may offer a unique tool for studying animal learning. In the first test of the utility of the apparatus, 3 Sprague-Dawley rats learned to activate the touch screen only after the touch-screen panel was made slightly movable. These animals then learned to discriminate visual stimuli presented on the computer monitor, but only after the food magazine and pellet dispenser were moved to the rear of the chamber opposite the stimulus display and response window. In a test of the utility of the modified apparatus, 6 Long-Evans rats learned to activate the touch screen and learned one of three different simple discriminations using computer-generated, visually presented stimuli. A basic method for training rats to activate the computer touch screen and for visual discrimination training is described. Results show that rats learned to activate the touch screen and discriminate visual stimuli presented on a computer monitor. Potential applications and advantages of the touch-screen-equipped rat operant conditioning chamber are discussed.

Journal of Neurophysiology, 2018

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 b...

Journal of Visualized Experiments

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopperswitching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be controlled by one computer.

PLOS ONE, 2022

The use of head fixation has become routine in systems neuroscience. However, whether the behavior changes with head fixation, whether animals can learn aspects of a task while freely moving and transfer this knowledge to the head fixed condition, has not been examined in much detail. Here, we used a novel floating platform, the "Air-Track", which simulates free movement in a real-world environment to address the effect of head fixation and developed methods to accelerate training of behavioral tasks for head fixed mice. We trained mice in a Y maze two choice discrimination task. One group was trained while head fixed and compared to a separate group that was pre-trained while freely moving and then trained on the same task while head fixed. Pre-training significantly reduced the time needed to relearn the discrimination task while head fixed. Freely moving and head fixed mice displayed similar behavioral patterns, however, head fixation significantly slowed movement speed. The speed of movement in the head fixed mice depended on the weight of the platform. We conclude that home-cage pre-training improves learning performance of head fixed mice and that while head fixation obviously limits some aspects of movement, the patterns of behavior observed in head fixed and freely moving mice are similar.