Abstract
Operant boxes enable the application of complex behavioural paradigms to support circuit neuroscience and drug discovery research. However, commercial operant box systems are expensive and often not optimised for combining behaviour with neurophysiology. Here we introduce a fully open-source Python-based operant-box system in a 5-choice design (pyOS-5) that enables assessment of multiple cognitive and affective functions. It is optimized for fast turn-over between animals, and for testing of tethered mice for simultaneous physiological recordings or optogenetic manipulation. For reward delivery, we developed peristaltic and syringe pumps based on a stepper motor and 3D-printed parts. Tasks are specified using a Python-based syntax implemented on custom-designed printed circuit boards that are commercially available at low cost. We developed an open-source graphical user interface (GUI) and task definition scripts to conduct assays assessing operant learning, attention, impulsivity, working memory, or cognitive flexibility, alleviating the need for programming skills of the end user. All behavioural events are recorded with millisecond resolution, and TTL-outputs and -inputs allow straightforward integration with physiological recordings and closed-loop manipulations. This combination of features realizes a cost-effective, nose-poke-based operant box system that allows reliable circuit-neuroscience experiments investigating correlates of cognition and emotion in large cohorts of subjects.
Highlights
Operant boxes are an important tool for pre-clinical drug discovery and biological psychiatry, enabling the use of well-controlled psychological tests that have been adapted for rodents from their human counterparts1,2
Taking advantage of the exchangeability of the 5 mm Opal-spacer layer that is available in different transmissivity (CutLaserCut, GB) which can be further adjusted with tape, we reduced light output to 95 lx of either yellow or white light, and, on session 14, further to 65 lx white light, which was kept because of the observed performance increase (Supplementary Fig. 3; all animals trained on stage 1 throughout), and was used for all subsequent training and experiments in this and the other cohorts
We developed a novel open-source 5-choice operant box system characterized by low cost, rapid turn-over between subjects, and compatibility with implanted and tethered animals for physiological manipulations and measurements
Summary
Operant boxes are an important tool for pre-clinical drug discovery and biological psychiatry, enabling the use of well-controlled psychological tests that have been adapted for rodents from their human counterparts. High cost constrains the ability to scale up cohort sizes and the efficient use of experimenter time Their mechanical design is often not optimised for neurophysiology, for example they often feature relatively deep recesses for poke holes and reward receptacles, which are poorly suited for testing implanted and tethered animals. Within the emerging field of low-cost open-source operant box systems and software to control operant experiments, our system is designed with a particular focus on the end-user, meeting five core demands: [1] Plug’n play set-up due to maximum integration of dedicated hardware and software components, [2] easy operation without requiring programming skills, [3] fast turn-over times between animals and direct extraction. Of both aggregated and millisecond time-resolved data, [4] optimal suitability of the box design, electronic interfaces, and software for simultaneous neurophysiological recordings and manipulations, and [5] low cost (well below < 1000 EUR per box) without any reliance on proprietary hardware or software
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