---
title: "Operant House: Open-source home-cage platform for automated mouse operant conditioning"
id: "plos-one-11-operant-house-a-versatile-open-source-platform-for-automated-operant"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-11-operant-house-a-versatile-open-source-platform-for-automated-operant"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0360626"
published_at: "2026-10-13T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Operant House: Open-source home-cage platform for automated mouse operant conditioning
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-11-operant-house-a-versatile-open-source-platform-for-automated-operant
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0360626)
- **Published At:** 2026-10-13T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The team developed the **Operant House**, an inexpensive, open-source device that places a touchscreen, retractable levers, and a water-reward port directly into individual mouse home cages to enable automated operant conditioning with minimal experimenter intervention. - The platform supports video monitoring (live and recorded) and two behavioral protocols used here: the **delayed non-matching-to-position (DNMTP)** test and a **two-choice spatial discrimination (TCSD)** test. - The system was supplied as two hardware versions: one integrating a laptop with an IR-touchscreen sensor, and a second using a single-board computer (Raspberry Pi 4) with IR camera–based image recognition. - Training began with a habituation and water-restriction schedule; sessions started at midnight with green-LED cues and ran until animals reached programmed water accesses or a session-time limit. - DNMTP comprised sequential blocks (VD1, VD2, DNMTP pre-acquisition, DNMTP) with stepwise criteria for progression; delay durations were randomized per trial and sensitivity analyses excluded trials with excessive actual delays. - TCSD used larger masks and a reversal rule: correct-side assignment reversed after >7 correct in the most recent 8 trials; VD1/VD2 visual discrimination preceded the TCSD block. - The authors applied both protocols to **App NL–G–F** knock-in mice and reported detectable working-memory deficits by 5 months of age; synaptic alterations in prefrontal cortex were reported as spatially heterogeneous and subtle, while conventional electrophysiology remained largely preserved. - The hardware can be assembled for roughly US $380–660 per unit with step-by-step instructions and open data/code on GitHub and Zenodo. - Individual housing is an inherent design constraint; the authors described live video monitoring and body-weight checks but did not report some specific measurements (for example, exact water volume consumed per animal was not measured).
## Clinical Analysis & Structured Key Points
Operant House: A versatile open-source platform for automated operant conditioning testing of mice in home cages | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Peer Review Reader Comments Figures Figures Abstract Operant conditioning is a powerful method for probing cognitive functions, yet its widespread use is constrained by low throughput, labor-intensive procedures, and high costs. Here, we developed “Operant House,” a low-cost, programmable device equipped with a touchscreen, retractable levers, and a water-reward port, designed to enable automated operant conditioning with minimal experimenter intervention in individually housed mice within their home cages. Although individual home-cage testing requires careful attention to animal welfare, the system permits continuous monitoring through live camera observation and recorded videos. As proof of concept, we implemented two cognitive protocols: a delayed non-match-to-position (DNMTP) test for assessing working memory and a two-choice spatial discrimination (TCSD) test involving working-memory-related processes and behavioral flexibility. Because working memory impairment is one of the earliest clinical features of Alzheimer’s disease (AD), we further applied these protocols to a knock-in mouse model carrying familial AD-associated amyloid precursor protein mutations ( App NL-G-F mice). Using this model, we detected significant working memory deficits as early as 5 months of age. At this age, we also detected subtle and spatially heterogeneous synaptic alterations in the prefrontal cortex, whereas conventional electrophysiological measures were largely preserved. Together, these findings highlight the Operant House as a cost-effective, scalable platform for assessing higher cognitive functions in mice, offering an accessible tool for investigating neurological and neuropsychiatric disease models. Citation: Otsuka S, Nakamura Y, Ito-Ishida A, Suzuki K, Ishikawa A, Matsuda K, et al. (2026) Operant House: A versatile open-source platform for automated operant conditioning testing of mice in home cages. PLoS One 21(10): e0360626. https://doi.org/10.1371/journal.pone.0360626 Editor: Mario Treviño Villegas, Universidad de Guadalajara, MEXICO Received: December 11, 2025; Accepted: September 29, 2026; Published: October 13, 2026 Copyright: © 2026 Otsuka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data for this study are publicly available from the Zenodo (doi.org/10.5281/zenodo.22019760) and GitHub ( https://shintaro18.github.io ) repositories. Funding: This study was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, in the form of a KAKENHI grant awarded to M.Y. (20H05628) and a KAKENHI grant awarded to A.I.-I. (22H05158); the Japan Society for the Promotion of Science (JSPS), Japan, in the form of KAKENHI grants awarded to M.Y. (22K21353 and 25H01011); and the Japan Agency for Medical Research and Development (AMED), Japan, in the form of a grant awarded to M.Y. (JP24zf0127010). MEXT: https://www.mext.go.jp/en/ JSPS KAKENHI: https://www.jsps.go.jp/english/e-grants/ AMED Moonshot Research and Development Program: https://www.amed.go.jp/en/program/list/18/03/001.html The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Introduction Operant conditioning has long been utilized in behavioral neuroscience to evaluate cognitive performance in a variety of species. In these tests, subjects are trained to perform specific behaviors, such as touching panels or pressing levers, in order to obtain rewards, such as water and food. Well-established protocols have been developed to measure various aspects of cognitive functions, including visual and spatial recognition, attention, impulsivity, working memory, and flexibility [ 1 – 5 ]. Operant conditioning serves as an unbiased assay, providing valuable insights into mouse cognition within the context of various neuropsychiatric and neurological disease models, including schizophrenia, autism spectrum disorders, and Alzheimer’s disease (AD). Conventional operant conditioning is typically conducted individually in a specialized apparatus under the supervision of an experimenter [ 6 ]. This process is labor-intensive and inefficient, as it must be repeated for each animal in a large cohort. Additionally, removing animals from their home cages—often during their inactive daytime period—for daily training sessions can induce significant stress and impaired performance. These limitations present substantial challenges to the widespread application of operant conditioning in disease model animals ( Fig 1A ). Download: PNG larger image TIFF original image Fig 1. Concept and the diagram of the Operant House. ( A, B ) Concept. In the conventional setup ( A ), animals must be transferred between their home cages and a dedicated operant conditioning chamber by an experimenter. In contrast, in the low-cost Operant House setup ( B ), operant tasks are performed automatically within individual home cages in parallel. ( C, D ) Block diagrams. To capture IR camera images and control peripheral devices, version 1 ( C ) uses a laptop PC, whereas version 2 ( D ) employs a single-board computer (Raspberry Pi 4). To detect nose-poke actions, version 1 ( C ) uses a touchscreen equipped with an IR sensor (AirBar) placed on the LCD monitor, while version 2 ( D ) utilizes image recognition of mouse movements captured by an IR camera. Several optional devices are also available, including an operation monitor, lever modules, and an AirBar. https://doi.org/10.1371/journal.pone.0360626.g001 To overcome these challenges, various devices have been developed to enable automated operant conditioning in the home cage, thereby reducing experimenter intervention and allowing training during the animals’ active period. Importantly, Poddar et al. developed the Automated Rodent Training System (ARTS), a low-cost, modular system that enabled fully automated, high-throughput home-cage training of rats in complex sensorimotor tasks [ 7 ]. Francis and Kanold subsequently developed the Psibox, a low-cost system designed to fit within conventional mouse cages that enabled automated positive-reinforcement training in the home cage and demonstrated its utility in an auditory detection task [ 8 ]. These studies established the feasibility and advantages of scalable, automated operant training in the home-cage environment. Other approaches have addressed complementary aspects of automated behavioral testing. For example, the CombiCage, which connects a home cage to a commercial operant chamber for the 5-choice serial reaction time task (5-CSRTT), was shown to achieve a tenfold increase in learning speed compared to conventional chambers for operant conditioning [ 9 ]. However, conducting simultaneous tests on multiple mice using such equipment is challenging due to its high cost and large size. An alternative approach is the IntelliCage system, which allows a group of individually tagged mice to be housed together in a single large cage for operant conditioning [ 10 – 15 ]. While the IntelliCage provides valuable population-level behavioral information, individual mouse behavior can be influenced by the presence of other mice in the same cage [ 16 – 19 ]. Building on these previous advances, for our intended applications we sought a platform that combined low per-unit cost and scalability with programmable touchscreen-based cognitive tasks, conventional lever-press paradigms, integrated video monitoring, and openly available hardware and software resources, while allowing each animal to be tested automatically in its own home cage. To meet these requirements, we developed a compact and affordable operant conditioning device, referred to as the “Operant House.” The Operant House is a fully programmable device equipped with a touchscreen and retractable levers for operant tasks, along with a water port for reward delivery, all integrated into an individually housed home cage. Because each device accommodates a single animal throughout the experimental paradigm, individual housing is an inherent limitation of the present design and requires careful attention to animal welfare, including the potential effects of social isolation. The Operant House therefore enables live observation and retrospective inspection of recorded task videos to facilitate monitoring of the animals’ general condition and possible signs of stress. This platform can be easily and inexpensively (US $380–660 per unit), assembled using readily available materials and a 3D printer, following step-by-step instructions provided on our website ( https://shintaro18.github.io/ ). As a result, this affordable platform enables automated behavioral testing with minimal experimenter intervention and parallel scaling of operant conditioning across individually housed mice in their home cages ( Fig 1B ). As proof of concept, we present two standard protocols for assessing working memory using Operant House: the delayed non-matching-to-position (DNMTP) test and the two-choice spatial discrimination (TCSD) test. Working memory, the capacity to temporarily maintain goal-relevant information to guide behavior, is frequently impaired across neurological and neuropsychiatric disorders. Notably, working memory deficits associated with prefrontal cortex dysfunction emerge during the preclinical stage of AD [ 20 – 22 ] and in AD model mice such as 3xTg, APP/PS1 and 5xFAD, in which familial AD-related mutations are overexpressed [ 22 – 25 ]. The recently developed App NL–G–F knock-in mice, which harbor three familial AD mutations in the amyloid precursor protein ( APP ) gene, are considered to more faithfully recapitulate human AD pathology because they lack artifacts caused by protein overexpression [ 26 ]. However, their behavioral phenotypes are generally milder than those of overexpression models, and the presence of early working memory deficits has remained inconsistent across studies [ 26 – 30 ]. Thus, using Operant House, we examined early cognitive performance in App NL–G–F mice using the DNMTP and TCSD tasks. We found deficits in these tasks as early as 5 months of age. These findings indicate that Operant House provides a sensitive, standardized platform for detecting subtle cognitive deficits and may facilitate investigations of cognitive impairment in neurological and neuropsychiatric disorders. Materials and methods Automated operant conditioning using the Operant House To begin habituation, mice were transferred from their home cages to the Operant House chamber between 9:00 a.m. and 12:00 p.m. The chamber was illuminated, and water was withheld until 9:00 p.m., resulting in 9–12 h of water restriction. Thereafter, the light was turned off, and mice were given ad libitum access to water until 9:00 a.m. the following day. From the second day onward, animals were subjected to either the DNMTP or TCSD paradigm. In both paradigms, each daily session began at midnight (0:00), signaled by illumination of a green LED and a brief 1-s water delivery. Sessions continued until the animal obtained a predetermined number of water accesses or until the maximum session duration elapsed. During each session, the cumulative duration of water access was continuously monitored to ensure adequate opportunity for water consumption. If the cumulative water-access duration fell below the predefined level (DNMTP: 160 s; TCSD: 300 s), supplemental water access was provided immediately after the session. Outside of task sessions, mice did not have access to water ( Fig 6A , 8A ). The actual volume of water consumed by each mouse was not directly measured. Body weight was monitored as part of the assessment of animal welfare during behavioral testing. To assess whether the DNMTP water-access regimen was associated with systematic changes in body weight, paired body-weight measurements obtained before and after testing were analyzed in six wild-type mice from independent experiments performed using Operant House version 2. These experiments used the same DNMTP water-access regimen (up to 80 water-access periods of 2 s each, corresponding to a maximum programmed water-access duration of 160 s per day), although other experimental parameters were not identical across all experiments. Pre- and post-testing body weights were compared using a paired t-test. The ceiling light remained off during behavioral sessions and during the dark phase (9:00 p.m. to 9:00 a.m.), except when punishment was delivered. Delayed non-matching to position (DNMTP) test A mask with three apertures, each aligned with an illuminated rectangular panel on the LCD screen, was used to present visual cues. The protocol consisted of three blocks ( Fig 5A ). Mice were advanced to the next block either after a predetermined number of days or when their performance reached a specified criterion level. Daily trials in each block were concluded when the total number of correct responses reached 80 or when 10 hours had elapsed since the start of the trials. Block 1−1: VD1 task ( Fig 5B ). In each trial, one of the three panels was randomly illuminated. When the subject touched the illuminated panel, the panel light was turned off, the green LED at the water port was activated, and the subject was allowed access to water for 2 sec. The water nozzle retracted 2 sec after detecting the subject’s nose poke into the water slit. Touching an unilluminated aperture was considered an incorrect response, resulting in a 2-sec timeout. The inter-trial interval (ITI) was set at 5 sec. Since many subjects did not initially recognize the association between panels and the water reward, they were given 1-sec water access if they did not respond to the illuminated panels for longer than 6 min (stimulus reward). VD1 was performed until the subject achieved 5 successive correct responses, at which point they were moved to visual discrimination task 2 (VD2). Block 1–2: VD2 task ( Fig 5C ). VD2 differed from VD1 in two ways. Firstly, the stimulus reward was not provided. Secondly, mice were punished with chamber light illumination (10 sec) when touching unilluminated panels. In the experiments involving ibotenic acid injection, VD2 was repeated for four days before the DNMTP pre-acquisition task. For experiments with the Alzheimer’s disease model, VD2 was repeated until the correct response exceeded 50%. The learning curves in control animals were similar in both conditions. In the analysis of wild-type animals using Operant House Version 2, VD2 was repeated until the correct response exceeded 65% for two consecutive days. Block 2: DNMTP pre-acquisition task ( Fig 5D ). The DNMTP pre-acquisition task was designed to help mice recognize the rules employed in the DNMTP task. At the beginning of the sample phase, either the left or right panel flickered. When the mice touched the flickering panel, the panel turned off. After 1 sec, the middle panel illuminated, signaling the start of the delay phase. This sequence was repeated once more to indicate the end of the delay phase. The delay phase lasted 1 sec, followed by the choice phase. In the choice phase, the panel located opposite the sample panel was illuminated, and touching this panel led to access to a water reward for 2 sec. Touching the same panel that had been illuminated during the sample phase was considered an incorrect response and resulted in a 10-sec chamber illumination punishment. The ITI was 30 sec. The DNMTP pre-acquisition task was performed for one day in Version 1. In Operant House Version 2, the DNMTP pre-acquisition task was repeated until the correct rate exceeded 85% for two consecutive days. Block 3: DNMTP task ( Fig 5E , F ). The DNMTP task was similar to the DNMTP pre-acquisition task, with the difference being that in the choice phase, both panels on the left and right sides were illuminated. The subject was required to remember the location of the sample panel and touch the correct panel in the choice phase. During the acquisition trials, the duration of the delay phase was set to 1 sec. The trials were repeated until the total success rate reached 80% (for App NL-G-F mice) or 75% (for experiments using Operant House Version 2) for two consecutive days. Most wild-type mice achieved this criterion within 1–2 weeks. Once the criterion was met, the duration of the delay was gradually increased ( Fig 5F ). To prevent mice from adapting to a fixed pattern of delay changes, two delay conditions (delay A and delay B) were randomly assigned on a trial-by-trial basis. To ensure that the delay schedules were identical across animals, the same randomization seed was used for all mice. Trials assigned to delay A were used for the working memory analysis. In some experiments, the actual delay duration, defined as the interval between touches of the sample and choice panels, was prolonged by behaviors such as eating or sleeping during the delay period and differed between experimental groups. The primary behavioral analyses therefore included all trials, and additional sensitivity analyses were performed using only trials in which the actual delay duration was below a predefined threshold (programmed delay × 1.3 + 10 s). The same criterion was applied to all groups and was based solely on actual delay duration, irrespective of trial outcome. Because selection based on actual delay duration could itself introduce bias, these delay-restricted analyses were considered sensitivity analyses rather than independent confirmatory tests. The numbers of retained and excluded trials are reported in the corresponding Results sections. Two-choice spatial discrimination (TCSD) test A mask with five apertures, each corresponding to illuminated rectangles on the LCD screen, was used to present visual cues. In the TCSD test, mice were required to memorize the correct position of the illuminated panel from the previous trial to receive a water reward. The experiment consisted of two blocks ( Fig 8A ). In the first block, mice were trained to associate touching the illuminated panels with the water reward by performing visual discrimination tasks (VD1 and VD2). The ITI was set at 5 sec. Daily trials were terminated either when the total number of correct responses reached 150 or when 6 hours had elapsed since the start of the trials. Block 1−1: VD1 task ( Fig 8B ). The VD1 task was conducted similarly to that of the DNMTP test ( Fig 5B ), with the exception that one of the five panels was randomly illuminated. The stimulus reward was also employed. Once the mice achieved five successive correct responses, they proceeded to the VD2 task. Block 1–2: VD2 task ( Fig 8C ). The VD2 task was also identical to the VD2 in DNMTP test, except that five panels were used. The VD2 task was repeated until the correct response rate exceeded 50%. Block 2: TCSD task ( Fig 8D ). In the TCSD task, two panels were simultaneously illuminated, and one of the two panels was randomly assigned as the correct choice at the beginning of trials. When the subject touched the correct panel, it was rewarded with 2 sec of water access. The incorrect choice was punished with chamber illumination for 5 sec. The position of the correct choice was reversed to the opposite side when the subject achieved more than 7 correct responses in the most recent 8 trials. The TCSD task was repeated for 3 days. Lever-pressing conditi
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