Automated Tests

Sylics offers a wide range of automated behavioural screening in a home-cage environment.

Spontaneous behaviors in PhenoTyper® cages

Sylics uses PhenoTyper® cages for mice and rats that allow continuous video tracking of rodents in a standardized environment that can be customized with a variety of add-ons (Noldus IT, The Netherlands). No human intervention is required for behavioural testing in a home-cage environment. This reduces stress of the animal, thereby facilitating high sensitivity and reproducibility of behavioral testing.

Mice display a variety of spontaneous behaviours in our automated home-cages (PhenoTyper), which are tracked at high resolution with video cameras and do not require human intervention. During the first three days in the PhenoTyper, our AHCODA analysis extracts 115 behavioural parameters (Loos et al 2014; Loos et al 2015). Tracking spontaneous behavior in the PhenoTyper allows rapid generation of a behavioral profile in novel mouse lines or sensitively studying therapeutic effects in disease models. For instance, At Sylics, we compared the spontaneous behavior of several mouse models of neurodegeneration models and aged cohorts of C57BL/6J (B6) mice up to 2 years of age. The analysis of spontaneous behavior clearly discriminated ageing from neurodegeneration in meta-analyses.

Spontaneous behaviour of mice in the automated home-cage (PhenoTypers) is tracked at high resolution and analysed by AHCODA. Highly discriminative parameters are produced, detecting changes in domains of motor function, circadian rhythm and others.
SOD1 mutant mice show progressive behavioral changes in the PhenoTyper including a reduced frequency to climb on top of their shelter.

Motor Function Spontaneous Behaviour

Sylics PhenoTyper cages are equipped with a shelter compartment, on which mice climb during bouts of activity in the dark phase (Loos et al 2014; Loos et al 2015). Reduced or absent shelter climbing is observed in mouse mutants with known motor function deficits, such as the SOD1 model of ALS. This test therefore detects the earliest stages of motor dysfunction. Please contact us for more information.

Anxiety Lightspot Test

We have developed a one-night anxiety test, which measures an animal’s response to an anxiogenic stimulus in an automated home-cage. A light spot is switched on during the dark phase of the mouse, which induces anxiety-like behaviour. This can be observed as avoidance behaviour (hiding in the shelter compartment). The Lightspot Test sensitively detects anxiety phenotypes in mice modeling neuropsychiatric and neurological disorders.

The light spot reduces time spent outside of the shelter in C57Bl/6 mice (orange lines), which is reversed by oral administration of the golden standard anxiolytic diazepam (purple lines) (Aarts et al 2015). Diazepam and other compounds are administered using a voluntary oral administration protocol developed by us. This circumvents anxiety induced by handling of the mouse.

When a bright LightSpot was switched on during the dark phase in the PhenoTyper cage, control treated mice spent less time outside of the shelter. This anxiety phenotype could be reversed with the golden-standard anxiolytic drug diazepam.
During avoidance learning in the PhenoTyper, one of the two entrances of the shelter is paired with illumination of the shelter. A shift in entering through non-illuminated entrance is an indication successful avoidance learning.

Avoidance Learning

Harm avoidance is relevant to the symptomatology of various psychiatric diseases. The avoidance learning test is a three-day automated home-cage approach to measure avoidance learning in a high-throughput fashion. In this test, mice learn to switch to their non-preferred shelter entrance, by pairing their preferred entrance with a mildly aversive stimulus (i.e. illumination of the shelter). This task was successfully used to characterize inbred strains and mutant mice with avoidance learning deficits (Maroteaux et al. 2012).

CognitionWall Discrimination Learning

Using the CognitionWall™, we developed a one-night automated test to efficiently identify discrimination learning impairments in mice, without time-consuming handling of mice. The CognitionWall is a wall with three entrances in front of a food dispenser. Mice are rewarded with a food reward when they choose to pass through one of the three entrances. The rate at which a mouse gains a relative preference for the rewarded entrance is used as a measure of discrimination learning.

Mouse models for Alzheimer’s disease also consistently display impaired discrimination learning in this test compared with wild-type littermates. In an APP/PS1 model this impairment was reduced by intra-hippocampal interventions, showing the involvement of the hippocampus in this task.

Acute induction of cognitive impairments with NMDA receptor antagonist MK-801 significantly increases the number of entries required for reaching the discrimination learning criterion.  Automated discrimination learning can be used to efficiently screen for therapeutics that restore cognition in these and our other disease models.

Intra-hippocampal infusion of Chondroitinase ABC (chABC) in 16 week old transgenic APP/PS1 mice restored cognitive function, confirming a role for the hippocampus in this task. Control groups were infused with the enzyme penicillinase (pnase).
MIce injected with a low dose of MK-801 show robust cognitive deficits in the CognitionWall discrimination learning task in the PhenoTyper.
During initial Discrimination Learning (DL) mice have to enter through the left entrance in order to receive a food reward behind the CognitionWall.
During Reversal Learning (RL) mice have to reverse, and enter through the right entrance in order to receive a food reward behind the CognitionWall, taxing their cognitive flexibility.

CognitionWall Reversal Learning (Cognitive Flexibility)

Sylics has developed a four-night automated CognitionWall™ test to efficiently identify reversal learning impairments in mice. The CognitionWall is a wall with three entrances in front of a food dispenser. Mice are rewarded with a food reward when they choose to pass through one of the three entrances, which is later switched to another entrance (reversal). The rate at which a mouse gains a relative preference for the newly rewarded entrance is used as a measure of reversal learning.

This reversal learning phase of the CognitionWall task has been validated by lesion of the orbital frontal cortex, which are know to impair cognitive flexilibyt and reversal learning in other tests (Remmelinks et al. 2016).

Self Paced 5csrt Task (Attention and Impulsivity)

The 5-choice serial reaction time task (5CSRTT) is the most widely used task measuring impulsive action and attention performance in mice, with excellent translation to humans. Sylics has developed a novel 5-CSRTT, without scheduled food deprivation and little animal handling (Remmelink et al 2017). Mice are allowed 24-h/day task access from their home-cage, during which they can self-pace task progression and earn unlimited food rewards depending on task performance.

The self paced 5-CSRTT test has the sensitivity to detect strain differences between C57BL/6J, DBA/2 J, BXD16 and BXD62 mice and is suitable for testing adolescent mice. Acute administration of the muscarinic acetylcholine receptor antagonist scopolamine impaired attentional performance, providing initial pharmacological validation of the task. The self paced 5-CSRTT test provides rapid assessment of impulsivity and attention in adolescent mouse models of psychiatric disorders.

Sylics' automated self-paced 5CSRT

Remmelink et al. (2017) Sci Rep

Remmelink E, Chau U, Smit AB, Verhage M, Loos M. A one-week 5-choice serial reaction time task to measure impulsivity and attention in adult and adolescent mice. Sci Rep. 2017 Feb 15;7:42519. doi: 10.1038/srep42519. PMID: 28198416; PMCID: PMC5309744.

Keywords: ADHD, psychiatry

Remmelink et al. (2016) Genes Brain Behav

Cognitive flexibility deficits in a mouse model for the absence of full-length dystrophin. Remmelink E, Aartsma-Rus A, Smit AB, Verhage M, Loos M, van Putten M. Genes Brain Behav. 2016 Jul;15(6):558-67. doi: 10.1111/gbb.12301. PMID: 27220066.

Keywords: Dystrophin, Duchenne, neuromuscular disorder, muscle disease

Aarts et al (2015) Behav Brain Res

Measuring anxiety in mice in an automated home-cage environment. Aarts E, Maroteaux G, Loos M, Koopmans B, Kovačević J, Smit AB, Verhage M, Sluis Sv; Neuro-BSIK Mouse Phenomics Consortium. The light spot test: Behav Brain Res. 2015 Nov 1;294:123-30. doi: 10.1016/j.bbr.2015.06.011. Epub 2015 Jun 10. PMID: 26072393.

Loos et al (2015) Mamm Genome

Within-strain variation in behavior differs consistently between common inbred strains of mice. Loos M, Koopmans B, Aarts E, Maroteaux G, van der Sluis S; Neuro-BSIK Mouse Phenomics Consortium, Verhage M, Smit AB. Mamm Genome. 2015 Aug;26(7-8):348-54. doi: 10.1007/s00335-015-9578-7. Epub 2015 Jun 28. PMID: 26123533.

Remmelink et al. (2015) Behav Brain Res

A 1-night operant learning task without food-restriction differentiates among mouse strains in an automated home-cage environment. Remmelink E, Loos M, Koopmans B, Aarts E, van der Sluis S, Smit AB, Verhage M; Neuro-BSIK Mouse Phenomics Consortium. Behav Brain Res. 2015 Apr 15;283:53-60. doi: 10.1016/j.bbr.2015.01.020. Epub 2015 Jan 17. PMID: 25601577.

Loos, Koopmans et al (2014) Plos One

Sheltering behavior and locomotor activity in 11 genetically diverse common inbred mouse strains using home-cage monitoring. Loos M, Koopmans B, Aarts E, Maroteaux G, van der Sluis S; Neuro-BSIK Mouse Phenomics Consortium, Verhage M, Smit AB. PLoS One. 2014 Sep 29;9(9):e108563. doi: 10.1371/journal.pone.0108563. PMID: 25264768; PMCID: PMC4180925.

Seigers et al (2015) Psychopharmacology (Berl)

Cognitive impact of cytotoxic agents in mice. Seigers R, Loos M, Van Tellingen O, Boogerd W, Smit AB, Schagen SB. Psychopharmacology (Berl). 2015 Jan;232(1):17-37. doi: 10.1007/s00213-014-3636-9. Epub 2014 Jun 4. PMID: 24894481.

Kramvis et al. (2013) Front Behav Neurosci

Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model. Kramvis I, Mansvelder HD, Loos M, Meredith R. Front Behav Neurosci. 2013 Nov 21;7:172. doi: 10.3389/fnbeh.2013.00172. PMID: 24312033; PMCID: PMC3836024.

Loos et al. (2012) Genes Brain Behav

Independent genetic loci for sensorimotor gating and attentional performance in BXD recombinant inbred strains. Loos M, Staal J, Pattij T; Neuro-BSIK Mouse Phenomics Consortium, Smit AB, Spijker S. Genes Brain Behav. 2012 Mar;11(2):147-56. doi: 10.1111/j.1601-183X.2011.00754.x. Epub 2011 Dec 13. PMID: 22098762.

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