IntelliCagefor Rat & Mouse
Cognitive & Behavioral
Screening of IndividualAnimals Living in Social Groups

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IntelliCage for Rats

IntelliCage for Mice

The IntelliCage is the only system on the market which combines grouphoused automated high-throughput screening in one home cage setup.
Simple to complex behavioral and conditioning tasks can be designed forcohorts of eight rats or 16 mice through RFID-tagged transponders, allowing
individually tailored protocols and recognition. The IntelliCage is comprisedof four operant conditioning corners, equipped with sensors for continuous
24-hour recording of behavioral events for real-time access to recorded
data anytime during ongoing experiments. IntelliCage offers exceptional
high standardization, reproducibility, and minimal workload, a frequent
requirement in biomedical, behavioral, neurobiological, pharmacological,
and genetic research.

IntelliCage: Unique features
Screening of Individuals in a Social Context
Efficient, up to eight rats or 16 mice perrespective rat or mice IntelliCage
Maximal Standardization & Reproducibility
High Validity(Minimal Human Intervention)
Fully Automated Task Performance
Broad Variety of Accessible DataFlexible Design of Paradigms

2

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IntelliCage: Applications
Being able to capture behavioral changes within the organism is an important partof biomedical research. The IntelliCage provides a broad variety of accessible data
for the following areas:

Behavioral Phenotyping
Automated high-throughput
behavioral phenotyping in a socialgroup. With highly standardized
phenotyping procedures, theIntelliCage covers multiple behavioral
and cognitive domains and allows
the comparison of multiple animalmodels of any disease or single/multiple gene knockouts.

True longitudinal studies
Animals either stay in the IntelliCagefor a prolonged period or re-visit thesystem several times during theirlifespan. Both approaches allow thedetection of age-dependent signs or
disease symptoms (e.g. Huntington’sdisease, Alzheimer’s disease, aging
research)

Mechanistic studies
Brain lesion studies for testing theinvolvement of specific structures indifferent behavioral domains, leading
to a better general understandingof behavior and underlying brain
functions.

Pharmacological studies
Drugs can be administered orally inthe drinking water or via osmotic
mini-pumps while the animals areundergoing behavioral or cognitive
testing. Highly standardized
conditions and protocols allow
comparisons of data of different
sexes, age groups, or genetic
backgrounds.

Wireless telemetry studies
The ability to combine theautomated behavioral phenotypingof the IntelliCage with ourwireless telemetry system Stellar
for simultaneous EEG, ECG,
Blood Pressure, and Activity
measurements.

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3IntelliCage: Technical details

Operant Corner:
The IntelliCage contains four identical operant
conditioning corners, each corner can accommodate
one mouse at a time and is equipped with two nose pokeholes left and right that give access to water bottles.
In response to the animal’s input, the IntelliCage can“react” via several Actors thereby shaping the animal’s
behavior according to individualized reinforcement
and conditioning protocols.

RFID Transponder:
Rice corn-shaped RFID-transponders are subcutaneously
injected within minutes, which allow individual recognition ofan animal within one IntelliCage. To increase high-throughput,
testing up to four IntelliCages can be connected to a single
computer (testing of up to 64 animals at the same time).

Sensors & Actors:
Sensors to register the animal’s behavior
IR light beamat the door
to water accessdetects nose poke
instancesentering
a corner

Temperature-sensitive
presence sensor
detects start, duration,and end of cornervisits (transponder)
Lickometer
entering
detects
the number
RFID antennaa cornerand duration ofidentifies the animal
tongue-contacts(transponder)
Motorizedwith drinking
entering a corner
doors allow/denynozzle
access to waterbottles at the nose
poke hole on bothsides of the corner(reinforcement)

4Actors to shape
the animal’sbehavior

Air puff valvesin each corner
may delivera punishment

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Multicolor LEDs
above the nose
poke holes act
as a conditional
stimulus

IntelliCage: SoftwareIntelliCage is run by a unique and user-friendly software package consisting of three separate
parts: Designer (allows programming of individual experimental designs), Controller (executes/monitors pre-programmed experimental designs and records data), and Analyzer (for efficient
data exploration, extraction, and export of recorded data, creating customized data-charts). The
software modules work as independent entities. Designer and Analyzer can be installed and run
on any computer you will need to comfortably program and analyze your experiments.
Clusters define the status of individual
corners and doors for each animal
assigned to this cluster.
Corners and doors can be independently
defined as correct, incorrect, or neutral
for multiple clusters.
Behavioral events Visits, Nosepokes,
Drinking are connected to different
actions Rewards, LED,
Air-puffs using logical units.
The experiments can be flexibly
designed, almost comparable toprogrammed codes, with the userfriendliness of a graphical user interface.
Several modules can be created in anexperiment and switched according
to the accomplishment of behavioral
challenge/task (switches between
clusters/modules that can be driven byindividual behavior)
Automated switches between clusters/
modules can be executed at fixed
day times by creating customized day
patterns.
After programming, the complete
experiment is stored in an experimental
file to be loaded into
the Controller Software.

1 2 3Specification ofhardware setup

Generationof the animal listcontaining individual
specifics such as ID,transponder number,sex, group, andassigned cluster

Programming
customized designs
containing one or
multiple experimental
phases

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5

Controller:
Run & visualize
experiments

01

Experimental files from the Designer
are loaded and executed by theController software

It extracts and stores all behavioral events(visits, nose pokes, licks), as well as
environmental data (lighting, temperature)from the incoming stream of Sensor data.

03

0205

Events and corresponding actions canbe monitored and visualized on-screen
during ongoing experiments in anoverview console view.

All data are retrievable from various tables showing
the correct or incorrect presence of individuals in
conditioning corners, location and correctness of nose
poke, incidences/extent of drinking behavior, and theoccurrence of negative reinforcement (air-puffs).

6

The data are accessible any time during theexperiment and behavioral parameters forindividual animals are further visualized indifferent graphs, allowing online-monitoringof all events and their temporal evolution.

The Controller can be programmed to sendalerts if individual animals show no visits orlicks during specified periods.

040706After experiments, raw data fromstandard tab-delimited text files aresaved into a zip-folder-archive which
can be loaded into the Analyzer.

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Analyzer:
Filter, graph & export data

1

Archive-files from the Controller are loaded into
the Analyzer, which uses Boolean operators to filter
data for different time-windows or conditions ofparticular interest (e.g. “all correct nose pokes ofcontrol animals during dark phase”).

2
Filtering efficiently facilitates data evaluation while
the original data remain accessible at any time.

3
All applied filters can be stored to re-apply themfor analyses of further experiments.

4All graphs and figures can be saved as different
image files.

5

Raw data tables, filtered data, as well as data
underlying graphs and figures can be exported as tabdelimited text-files for more sophisticated analyses
in other programs such as standard graphical andstatistical packages, e.g. FlowR (see “add ons”).

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7FlowR-Software by XBehavior:
Statistical analysis & visualization optimized for IntelliCage data

A graphical user interface
translating R-script
units into graphicallyarranged statistical
workflows.

01

02
Click and go - Datavisualization andstatistical analyses
available with justa click of the mouse.

Users are seamlessly
guided throughthe analysis
process without
programming efforts.

04
03IntelliCage Basic Bundle
with pre-programmed
workflows for datapreparation,
phenotyping, side
preference-analysis, place
preference-analysis,
assessment of general activity

IntelliCage allows the transfer of multiple established behavioral paradigms into
an automated setup.
Morris Water-Maze

Vogels’ Conflict-Test

Radial Arm-/Y-/T-Maze

Novel-Object-Preference-Tests

Open-Field

Operant-Conditioning (Fixed-/Progressive-Ratio,equivalent to SkinnerBox)

Sucrose-Preference
Social-Defeat
Competition- and Hierarchy-Tasks

8Many other procedures for assessing generalprocesses of learning & memory, executivefunction, behavioral flexibility, cognitive rigidity,
effort choice behavior, circadian activity, acute/chronic stress- or drug-treatment effects.

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The enormous flexibility enables you to set up individual test batteries for behavioral and cognitive
assessment of animal models on:
Autism, Alzheimer’s Disease, Parkinson’s Disease, Dementia, Epilepsy, Anxiety Disorders,Depression, Anhedonia, Neophobia, Pain, Obesity, Stress Disorders, Cognitive Disorders, Aberrantsocial behavior (non-exhaustive).
IntelliCage – Behavioral Paradigms
A. Spontaneous Behavior
1. Free Adaptation*

Animals are adapted to the use of corners to access water.

2. Nosepoke Adaptation*

Nosepoking is required to access water bottles – equivalent to Fixed-Ratio-1schedules.

B. Spatial and Temporal
3. Place Learning*

Access to water is restricted to defined corners in space.

4. Avoidance Learning

Visits to defined corners in space are punished with air-puffs – equivalent to Vogel
Test.

5. Reversal Learning*

A reward corner is changed to reverse prior spatial preference.

6. Alternation

A reward side is alternated.

7. Serial Reversal

A reward corner is changed serially according to the animal’s performance.

8. Patrolling

Reward corner shifts (anti-)clockwise after a correct response(visit, nose poke, or drink) – similar to spatial learning in an 8-arm radial maze.

9. Coverage

Rewards reinforce regular corner switching (random sequence patrolling).

10. Drinking Sessions /Temporal Learning*

Access to water bottles is restricted to certain day & night times.

C. Social and Others
11. Competition / Hierarchy
All individuals have water access restricted to certain corners and day & nighttimes.
Analysis
12. Differential
Synchronization

Single individuals are assigned to different day & night patterns of water access totest for social cohesion.

D. Discrimination Learning and Preferences
13. Light Discrimination(LED Scheme)

Reward corners are indicated by the light regime.

14. Taste Aversion

Consumption pattern reveals taste aversion.

15. Compound Cue

Water bottles are inoculated with different drugs.

E. Memory
16. Impulsivity & Delay
Discounting

Animals can have immediate access to a plain reward (water) or wait for a predefined delay period to get access to a more salient reward (sucrose solution).

17. Attentional ShiftSide and number of LEDs indicating reward are randomly shifted for each visit.

18. Neophobia

Olfactory/gustatory cues in corners/bottles are switched to induce novelty.

19. Conditioned Aversion

Probe trial tests for acquired aversion to unconditioned reinforce.

F. Operant Conditioning
20. Conditioned Stimulus(LED Scheme)

The conditioned stimulus (lights on/off) indicates reward side(water bottle access).

21. Fixed Ratio*

A fixed number of responses is required to access a reward.The ratio depends onreward salience (determined by place).

22. Progressive Ratio*

The requirement to access a reward increases on a trial-by-trial basis.

23. Impulsivity & Diff.
Reinforcement ofLowResponding (DRL)*

Progressive response inhibition by reinforcing long time intervals betweenresponse(nose poke) incidents.

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9Add-Ons: Expand the IntelliCage to a multi-arena system
AnimalGate:
Selective passage of specificanimals for extended functionality

Senses the direction of movement &allows/denies passage to satellite cage

Extends the IntelliCage to measure food/liquid consumption

Allows black- or whitelisting of individuals

Allows additional application of different
treatments to individuals without handling

Measures body weight of passing miceSocialBox:
Monitoring of social
behavior using theIntelliCage

Used for different tasks including social
interactions between animals

lighting, temperature, color or padding, byolfactoric/acoustic devices or novel objects

Monitoring of individual spatial preference/
avoidance patterns by creating different
environments in the boxes (e.g. differential

Up to four SocialBoxes can be added to one
IntelliCage creating five compartments of amulti-arena system.

10

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Running wheel:
Monitoring of motor activity using the IntelliCage
Up to four running wheels can be added to one IntelliCage
Monitoring of individual mice motor movement on running wheel directly from Intellicagecontroller

Selected Publications
Sun L et al. (2021) Antidepressant treatment is associated with epigenetic alterations ofHomer1 promoter in a mouse model of chronic depression. J Affect Disord. 2021; 279: 501–509.
Kiryk A et al. (2020) IntelliCage as a tool for measuring mouse behavior – 20 years perspective.
Behav Brain Res. 2020; 388:112620.
Mehr A et al. (2020 Lack of APP and APLP2 in GABAergic Forebrain Neurons Impairs Synaptic
Plasticity and Cognition. Cereb Cortex. 2020; 30: 4044–4063.
van Dijk RM et al. (2019) Consistent within-group covariance of septal and temporal hippocampal
neurogenesis with behavioral phenotypes for exploration and memory retention across wild
and laboratory small rodents. Behav Brain Res. 2019; 372: 112034.
Hardt S et al. (2019) Distal infraorbital nerve injury: A model for persistent facial pain in mice.
Pain. 2019; 160: 1431–1447.
Dere E et al. (2018) Cognitive, emotional and social phenotyping of mice in an observerindependent setting. Neurobiol Learn Mem; 150:136-150
Voikar V et al. (2017) Automated dissection of permanent effects of hippocampal or prefrontal
lesions on performance at spatial, working memory and circadian timing tasks of C57BL/6 micein IntelliCage. Behav Brain Res; pii: S0166-4328(17)30962-2.[Epub ahead of print]
Stefaniuk M et al. (2017) Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central
Amygdala in Control of Alcohol-Seeking Behavior. Biol Psychiatry; 81(11):907-917.
Jastrzebska K et al. (2016) Loss of NMDA receptors in dopamine neurons leads to thedevelopment of affective disorder-like symptoms in mice. Sci Rep. 2016 Nov 17;6:37171.
Masuda A et al. (2016) Cognitive deficits in single App knock-in mouse models. Neurobiol Learn
Mem; 2016 Nov;135:73-82
Heidari M et al. (2016) Brain iron accumulation affects myelin-related molecular systems implicatedin a rare neuro- genetic disease family with neuropsychiatric. Mol Psychiatry 2016; 1-9
Benner S et al. (2015) Environmental insults in early life and submissiveness later in life inmouse models. Front Neurosci 2015; 9:91
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11Vannoni E et al. (2014) Spontaneous behavior in the social homecage discriminates strains,
lesions and mutations in mice. Methods 2014; 234:26-37
Smutek M et al. (2014) A model of alcohol drinking under an intermittent access schedule usinggroup-housed mice. PLoS One; 9(5):e96787
Too LK et al. (2014) The pro-inflammatory cytokine interferon-gamma is an important driverof neuropathology and behavioural sequelae in experimental pneumococcal meningitis. Brain
Behav Immun 2014; 40:252-68
Puscian A et al. (2014) A novel automated behavioral test battery assessing cognitive rigidity
in two genetic mouse models of autism. Front Behav Neurosci; 8(140):1-11
Knapska E et al. (2013) Reward learning requires activity of matrix metalloproteinase-9 in thecentral amygdala. J Neuroscience; 33(36):14591-14600
Branchi I et al. (2013) Antidepressant treatment outcome depends on the quality of the living
environment: a pre-clinical investigation in mice. PlosOne; 8(4): e62226
Parkitna JR et al. (2013) Novelty-seeking behaviors and the escalation of alcohol drinking after
abstinence in mice are controlled by metabotropic glutamate receptor 5 on neurons expressing
dopamine D1 receptors. Biological Psychiatry; 73(3): 263-70

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https://www.jove.com/video/58009/automated-long-term-behavioral-assay-for-cognitivefunctions-multiple

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preparing these documents, TSE Systems makes no representations and gives no warranties
of whatever nature in respect of these documents, including but not limited to the accuracy
or completeness of any information, facts and/or opinions contained therein.
Copyright © 2021 TSE Systems - All rights reserved.

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