The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation

Ceasing an ongoing motor response requires action cancelation. This is impaired in many pathologies such as attention deficit disorder and schizophrenia. Action cancelation is measured by the stop signal task that estimates how quickly a motor response can be stopped when it is already being executed. Apart from human studies, the stop signal task has been used to investigate neurobiological mechanisms of action cancelation overwhelmingly in rats and only rarely in mice, despite the need for a genetic model approach. Contributing factors to the limited number of mice studies may be the long and laborious training that is necessary and the requirement for a very loud (100 dB) stop signal. We overcame these limitations by employing a fully automated home-cage-based setup. We connected a home-cage to the operant box via a gating mechanism, that allowed individual ID chipped mice to start sessions voluntarily. Furthermore, we added a negative reinforcement consisting of a mild air puff with escape option to the protocol. This specifically improved baseline inhibition to 94% (from 84% with the conventional approach). To measure baseline inhibition the stop is signaled immediately with trial onset thus measuring action restraint rather than action cancelation ability. A high baseline allowed us to measure action cancelation ability with higher sensitivity. Furthermore, our setup allowed us to reduce the intensity of the acoustic stop signal from 100 to 70 dB. We constructed inhibition curves from stop trials with daily adjusted delays to estimate stop signal reaction times (SSRTs). SSRTs (median 88 ms) were lower than reported previously, which we attribute to the observed high baseline inhibition. Our automated training protocol reduced training time by 17% while also promoting minimal experimenter involvement. This sensitive and labor efficient stop signal task procedure should therefore facilitate the investigation of action cancelation pathologies in genetic mouse models.

Automated summary

The stop signal task measures the ability to cancel ongoing motor responses, often impaired in disorders like ADHD and schizophrenia. While traditionally studied in rats, a fully automated home-cage setup for mice has improved efficiency. The new setup also allows for lower intensity of the stop signal and quicker training times, reducing SSRTs and improving baseline inhibition.