IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system

Abstract

IntelliCage for mice is a rodent home-cage equipped with four corner structures harboring symmetrical double panels for operant conditioning at each of the two sides, either by reward (access to water) or by aversion (non-painful stimuli: air-puffs, LED lights). Corner visits, nose-pokes and actual licks at bottle-nipples are recorded individually using subcutaneously implanted transponders for RFID identification of up to 16 adult mice housed in the same home-cage. This allows for recording individual in-cage activity of mice and applying reward/punishment operant conditioning schemes in corners using workflows designed on a versatile graphic user interface. IntelliCage development had four roots: (i) dissatisfaction with standard approaches for analyzing mouse behavior, including standardization and reproducibility issues, (ii) response to handling and housing animal welfare issues, (iii) the increasing number of mouse models had produced a high work burden on classic manual behavioral phenotyping of single mice. and (iv), studies of transponder-chipped mice in outdoor settings revealed clear genetic behavioral differences in mouse models corresponding to those observed by classic testing in the laboratory. The latter observations were important for the development of home-cage testing in social groups, because they contradicted the traditional belief that animals must be tested under social isolation to prevent disturbance by other group members. The use of IntelliCages reduced indeed the amount of classic testing remarkably, while its flexibility was proved in a wide range of applications worldwide including transcontinental parallel testing. Essentially, two lines of testing emerged: sophisticated analysis of spontaneous behavior in the IntelliCage for screening of new genetic models, and hypothesis testing in many fields of behavioral neuroscience. Upcoming developments of the IntelliCage aim at improved stimulus presentation in the learning corners and videotracking of social interactions within the IntelliCage. Its main advantages are (i) that mice live in social context and are not stressfully handled for experiments, (ii) that studies are not restricted in time and can run in absence of humans, (iii) that it increases reproducibility of behavioral phenotyping worldwide, and (iv) that the industrial standardization of the cage permits retrospective data analysis with new statistical tools even after many years.

Neuroeducación y Medicina Conductual: Herramientas Indispensables para mejorar la Calidad de Vida en Hospitales y en Casa

“…Para que la medicina conductual y la neuroeducación puedan ponerse al servicio de los contextos hospitalarios, es necesario que, se puedan generar modelos eficientes y prácticos en lo relativo a la atención escalonada o por fases, pues así se conseguiría maximizar las interacciones entre todos los bloques de pacientes y los agentes proveedores de servicios de salud, entre los que se cuentan a la medicina general, la enfermería, todas las especialidades médicas y demás servicios sanitarios y sociales de los hospitales, clínicas y centros de salud en los que sea posible contar con psicólogos expertos en medicina conductual y en neuroeducación, ya que, cuando se integran estas dos disciplinas científicas, las fortalezas en cuanto a automonitoreo y autorregulación de los pacientes en casa respecto de sus diagnósticos particulares, tiende a aumentar de forma exponencial (Borg, Öberg, Nilsson, Alfredsson, Söderlund & Bäck, 2023;Fritz & Overmeer, 2023;Lipp, Krackow, Turkes, Benner, Endo & Russig, 2024).…”

Appetitively motivated tasks in the IntelliCage reveal a higher motivational cost of spatial learning in male than female mice

“…Thus, to be valid, cognitive tests must be applicable to subjects of both sexes. Given that the IntelliCage system is generally suitable for testing mice of both sexes ( Kiryk et al, 2020 ; Lipp et al, 2024 ), we deemed it necessary to assess task performance in our appetitively motivated protocols for IntelliCage not only in female but also in male mice. The attractiveness of saccharin, the sweet reward used in our study, to male C57BL/6 mice is well-documented ( Bachmanov et al, 2001 ).…”

“…Behavioral testing was conducted in the IntelliCage system (TSE Systems, Bad Homburg, Germany), which is a fully automated cage system designed for the assessment of cognitive abilities in group-housed small rodents ( Lipp, 2005 ; Kiryk et al, 2020 ; Lipp et al, 2024 ). The apparatus ( Figure 1A ) consists of a polycarbonate cage (20.5 cm high, 58 × 40 cm top, 55 × 37.5 cm bottom, Techniplast, 2000P, Buguggiate, Italy) equipped with four triangular operant test chambers (15 × 15 × 21 cm) fitted into each corner.…”

Environmental enrichment: a systematic review on the effect of a changing spatial complexity on hippocampal neurogenesis and plasticity in rodents, with considerations for translation to urban and built environments for humans

“…Furthermore, new paradigms could be employed in rodents to explore the effects of spatial complexity, namely: (a) smart cages, i.e., complex cages containing technological interactive elements that allow automated home-cage behavioral monitoring ( Mingrone et al, 2020 ; Voikar and Gaburro, 2020 ; d'Isa and Gerlai, 2023 ; Kahnau et al, 2023 ; Lipp et al, 2024 ); (b) seminatural environments, i e. housing environments that reproduce in the laboratory elements of the natural habitat of the hosted species ( Hernández-Arteaga and Ågmo, 2023 ); (c) freely accessible complex mazes connected directly to the home-cage, such as the automated eight-arm radial maze designed by the Julius Emmrich laboratory ( Mei et al, 2020 ; Kohler et al, 2022 ); (d) radio-collars allowing radio-tracking of free-ranging rodents living in their natural habitat ( Stradiotto et al, 2009 ; Bonacchi et al, 2021 ).…”