Rodent Behavioral Assessment in the Home Cage Using the SmartCage™ System (2012)

The combination of molecular manipulation of gene expression and behavior endpoint phenotypic analysis has uncovered numerous novel gene functions and provided unprecedented opportunities for new drug development. To facilitate investigation of diverse behavioral processes, we have developed a home cage monitoring system for automated rodent neurobehavioral phenotypic analysis and higher-throughput in vivo drug screening. This system termed SmartCage™ measures rodents’ behavior in their home cages as a significant endpoint. The SmartCage™ system consists of multiple instrument platforms that interface with ordinary rodent home cages. Each SmartCage™ is comprised of multiple sensors including a floor-vibration sensor, an infrared (IR) matrix and flexible modular devices. This system is noninvasive and allows the animal to be tested in its home cage that has bedding, food, and water, making it appropriate to monitor animals for days or weeks. The automated measurements include wake and sleep/inactive states. The active parameters include locomotion, rearing, and animal movement patterns, for example, rotations (cycling). In validating the system, we first compared it with conventional technologies, e.g., video camera recording. The results indicate a strong correlation between imaging tracking and IR detection. Next we used pharmacological tools (both stimulant and activity inhibitors) to further validate the system, which demonstrated that SmartCage™ is sensitive enough to detect drug-induced increases and decreases in activity levels. Secondly, wake and sleep state automated classification by the SmartCage™ was validated by comparing it with simultaneously recorded electroencephalograph (EEG)/electromyograph (EMG) data. This comparison confirms that the floor-sensor can provide up to 85–90% accuracy in estimating sleep states. Using modular devices incorporated into the SmartCage™ platform, other behavioral measures can be collected. For example, a new rotarod device can be flexibly installed in the SmartCage™ system. The manual rotarod test can be conducted in a similar manner as the conventional rotarod test. That is, the researcher placing the mouse onto the rod and then start the test. Using this new device, spontaneous performance of rotarod test is automatically initiated by the animal at its home cage. The duration of staying on the rotating rod and numbers of spontaneous performance are significantly different between middle cerebral arterial occlusion (MCAO) and sham control mice. Another modular insert includes a dark box that can be placed directly into the animal’s home cage and our initial tests indicate that the SmartCage™ can detect diazepam-induced anxiolytic effects. The result is comparable to those obtained using conventional anxiety tests such as the elevated plus T-maze and Zero-maze. In conclusion, this noninvasive integrated home cage monitoring system, SmartCage™, can provide an automated assessment of rodent behavior to identify gene-altered phenotypes, to facilitate initial in vivo drug screening, and to rapidly filter out neurobehavioral toxic compounds prior to testing in individual disease models.