AutonoMouse: High throughput operant conditioning reveals progressive impairment with graded olfactory bulb lesions

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 somewhat lagged behind. 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, demonstrating that while odour discrimination in general is robust to even most extensive disruptions, small olfactory bulb lesions already impair odour detection. Discrimination learning of similar mixtures as well as learning speed are in turn reliably impacted by medium lesion sizes. The modular nature and open-source design of AutonoMouse should allow for similar robust and systematic assessments across neuroscience research areas.

High-Throughput Automated Olfactory Phenotyping of Group-Housed Mice

“…These results show that it is feasible to characterize previously untested mouse lines using this automated approach. Similarly, the "AutonoMouse" variant of this setup (see the section "Materials and Methods" for description of the differences between the variants) has recently been used to rigorously quantify the impact of graded olfactory bulb lesions on odor discrimination (Erskine et al, 2019). Taken together, the results gathered independently using the different variants clearly demonstrate the versatility and reproducibility of this approach to automated olfactory phenotyping.…”

“…Recent work has shown that simultaneous behavior testing of large cohorts of mice can be achieved by housing a group of up to 14 mice in a home cage with free access to a behavioral testing area ("AutonoMouse") (Erskine et al, 2019). Such a design can house two cohorts of mice (i.e., genetically modified mice and their littermate controls) for simultaneous behavior testing using a single olfactometer, thereby reducing potential sources of variation.…”

“…Such a design can house two cohorts of mice (i.e., genetically modified mice and their littermate controls) for simultaneous behavior testing using a single olfactometer, thereby reducing potential sources of variation. As animals are able to freely access the testing area whenever they are motivated to obtain a reward, this setup produces a large number of trials performed by highly incentivized animals (Erskine et al, 2019).…”

An automated homecage system for multiwhisker detection and discrimination learning in mice

“…Automated behavioral paradigms, such as the IntelliCage (17–20), have been used in other studies to train animals for discrimination of odors (21–23), oriented lines (24,25), and auditory tones (26–28). Several studies also used automated set-ups for motor control tasks (29–32).…”

Odor Stimuli: Not Just Chemical Identity

“…The recent work of the group of Schäfer analyzed the effect in a windtunnel on a smaller spatial scale (source separation around 0–50 cm, downwind distance 40 cm, air speed around 552 cf/m 10 ). With Aurora Scientific they developed the first “dual-energy photoionization detector” and recorded the evolution of odorant concentration emitted from two sources, either mixed together or separated (Erskine, 2018; Erskine et al, 2019). The analysis of temporal correlation of the odor signal showed that “source separation” can be accurately predicted.…”