AutonoMouse: High throughput automated operant conditioning shows progressive behavioural 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 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.

Mouse Academy: high-throughput automated training and trial-by-trial behavioral analysis during learning

“…2a, 2a’ and 2a’’ ). All the mice eventually reached a >83% performance level, comparable to what mice achieve in similar tasks 19,27 . The GLM makes a prediction for the outcome of each trial based on a weighted combination of several input variables: the current visual stimulus, a constant bias term, and three terms representing the history of previous trials ( Fig.…”

“…Thus, eliminating the requirement for human intervention, as in Mouse Academy, likely reduces experimental variation. In another design, a training setup is incorporated within the animals’ home cage 17–19 . By contrast, Mouse Academy separates the functions of housing and training, and that modular design allows easy adaptation to a different purpose.…”

“…The training procedures are often time-consuming, requiring several days to many weeks 8,9 , depending on the task. Although there have been advances in training automation, existing systems either require an experimenter to move animals from the home cage to the training apparatus 14–16 , or training animals within their own cages 17–19 . The former introduces additional sources of variability 20,21 , and the latter precludes tasks that require a large training arena.…”

Mammalian olfaction is a high temporal bandwidth sense

“…In AutonoMouse, groups of mice (up to 25) implanted with an RFID chip are housed in a common home cage (Fig 2a, for detailed description see Erskine et al, 2019). Within the common home cage of AutonoMouse, mice have free access to food, social interaction and environmental enrichment.…”

“…A multiple channel version of the odour delivery device in turn could reliably produce odour pulses with different temporal correlation structures (Fig 1h). In order to assess whether mice could discriminate between such stimuli at different frequencies, we developed an automatic operant conditioning system ("AutonoMouse", Fig 2a, Supp Video 1 (Erskine et al, 2019) ), where cohorts of up to 25 mice could be trained in operant conditioning tasks simultaneously. Mice in the system were group-housed and RFIDtagged for individual identification, remaining in the apparatus for periods of up to 18 months.…”