Abstract
Operant conditioning is a crucial tool in neuroscience research for probing brain function. While molecular, anatomical and even physiological techniques have seen radical increases in throughput, efficiency, and reproducibility in recent years, behavioural tools have seen much less of an improvement. Here we present a fully automated, high-throughput system for self-initiated conditioning of up to 25 group-housed, radio-frequency identification (RFID) tagged mice over periods of several months and >10^6 trials. We validate this “AutonoMouse” system in a series of olfactory behavioural tasks and show that acquired data is comparable to previous semi-manual approaches. Furthermore, we use AutonoMouse to systematically probe the impact of graded olfactory bulb lesions on olfactory behaviour and resolve the long-standing conundrum about the apparent lack of impact of lesions on olfactory abilities. The modular nature and open-source design of AutonoMouse should allow for similar robust and systematic assessments across neuroscience research areas.