Anxiety/activity Tests

Sylics offers a variety of anxiety and activity tests.

Automated Home Cage Based Dissection of Activity

Mice display a variety of spontaneous behaviours in our automated home-cages. In these PhenoTyper cages (Noldus IT, The Netherlands) mice are tracked at high resolution with video cameras, without any 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. Please contact us for more information.

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.
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.

Automated Home Cage Based 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 (orange 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. Please contact us for more information

Elevated Plus Maze

The Elevated Plus Maze (EPM) is a widely used test to measure anxiety in mice. Mice are introduced into the elevated plus maze, which contains two open and two enclosed arms. The time spent on the open arms is a measure of anxiety-related behaviour. We have used the EPM for the characterization of commonly used inbred strains (Loos et al 2009), as well as mouse models of neurodevelopmental disorders such at the Stxbp1 model (Kovacevic et al 2018). Please contact us for more information.

The elevated plus maze contains two open and two enclosed arms. Mice are reluctant to enter the open arms, which is a measure of anxiety-related behaviour.
The illuminated side of the light-dark box. Mice are introduced into the dark compartment and a motorized provides access brightly lit compartment.

Light Dark Box

The Light Dark Box (LDB) is used to assess anxiety in mice. Mice are introduced into the dark compartment of the LDB. After a delay, the motorized door opens, providing access to an identical sized compartment which is brightly lit. The time spent in the light compartment is a measure of anxiety-related behaviour. We have used the LDB for the characterization of commonly used inbred strains (Loos et al 2009), as well as numerous disease models. Please contact us for more information.

Novelty Induced Hypophagia

The Novel Induced Hypophagia (NIH) test is used to assess anxiety in mice. Prior to testing, mice are familiarized to a highly palatable snack placed into a familiar metal food cup in the home-cage. On the testing day hypophagia is assessed by transferring mice to a novel cage with containing the metal cup with the familiar snack. The latency to start eating the snack is a measure of NIH. Commonly used inbred strains differ tremendously in NIH (Loos et al 2009).

Although mice are highly motivated to eat from a familiarized highly palatable snack (a few crumbs of cream cracker), the novel environment induces anxiety-related behavior and a delay in consumption of the snack.
When introduced into anxiogenic brightly lit Open Field, mice will typically start exploring the corners and walls first, and eventually enter into the centre.

Open Field Test

This is probably the most frequently used test in behavioral pharmacology to measures changes in activity/anxiety-related behaviour in rodents. Due to the novelty of the open white arena, rodents will explore this. Gross changes in motor function may be detected by tracking changes in the total distance moved or velocity. Alterations in emotionality may be detected by changes in the time spent in the center area of the arena. Please contact us for more information.

Running wheel activity

When housed in a cage that is equipped with a running wheel, mice will voluntarily start running in it. Rotations are detected at high temporal resolution and subsequently analyzed with Sylics’ AHCODA software, to generate parameters of activity and circadian rhythms. Voluntary wheel running can be used to assess the physical performance, model exercise training, and general health of mice. This setup is therefore useful to detect pharmacological effects on activity, circadian rhythms, and endurance.

When placed in a cage equipped with a Running Wheel, mice require 5 – 10 days to reach a stable activity level and circadian rhythm (~8 days for this mouse).
A fear conditiong box, to measure contextual fear learning and memory.

Fear Conditioning

Fear Conditioning (FC) is a widely used test to assess anxiety-related phenotypes in mice, as well as learning and memory. In the FC test, mice learn to associate an aversive stimulus with a neutral context or stimulus. This results in freezing in response to the previously neutral stimulus or context. The FC test has been instrumental in detecting learning and memory deficits in Alzheimer's disease models, mouse models of rare genetic diseases and neurodevelopmental disorders. Please contact us for more information.

Kovacevic et al (2018) Brain

Kovacevic J, Maroteaux G, Schut D, Loos M, Dubey M, Pitsch J, Remmelink E, Koopmans B, Crowley J, Cornelisse LN, Sullivan PF, Schoch S, Toonen RF, Stiedl O, Verhage M. Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy. Brain. 2018 May 1;141(5):1350-1374. doi: 10.1093/brain/awy046. PMID: 29538625; PMCID: PMC5917748. https://pubmed.ncbi.nlm.nih.gov/29538625/

Keywords: STXBP1, Munc-18, EEG

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. https://pubmed.ncbi.nlm.nih.gov/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. https://pubmed.ncbi.nlm.nih.gov/26123533/

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. https://pubmed.ncbi.nlm.nih.gov/25264768/

Loos et al. (2009) Genes Brain Behav

Activity and impulsive action are controlled by different genetic and environmental factors. Loos M, van der Sluis S, Bochdanovits Z, van Zutphen IJ, Pattij T, Stiedl O; Neuro-BSIK Mouse Phenomics consortium, Smit AB, Spijker S. Genes Brain Behav. 2009 Nov;8(8):817-28. doi: 10.1111/j.1601-183X.2009.00528.x. Epub 2009 Sep 9. PMID: 19751396.

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