Cognitive Tests
Sylics offers a wide range of tests to measure cognitive functions in mice and rats.
5 Choice Serial Reaction Time Task
The 5-choice serial reaction time task (5CSRTT) is the most widely used task measuring impulsive action and attention performance. In the 5CSRTT, mice are required to respond to a brief light stimulus in one of five response apertures. The number of premature responses before the stimulus light switches on is a measure of impulsivity. Omissions and accuracy of responding are measures of attention. Sylics’ researchers and technicians have contributed their 5CSRTT expertise to numerous studies employing this task (Pattij, Loos et al 2007; Loos et al 2009; Loos et al 2010; Counotte, Loos et al 2011, Guillem, Loos et al 2011; Loos et al 2012; Loos et al 2013; Kramvis, Loos et al 2013).
Self Paced 5 Choice Serial Reaction Time Task
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 provides rapid assessment of impulsivity and attention in adolescent mouse models of psychiatric disorders.
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
With the CognitionWall™, Sylics researchers have developed a one-night automated test to efficiently identify discrimination learning impairments in mice, without time-consuming handling of mice (Remmelink et al. 2016). Mice are rewarded with a food reward when they choose to pass through one of the three entrances of the CognitionWall. The rate at which a mouse gains a relative preference for the rewarded entrance is used as a measure of discrimination learning. Acute induction of cognitive impairments with NMDA receptor antagonist MK-801 increases the number of entries required for reaching the discrimination learning criterion.
CognitionWall Reversal Learning (Cognitive Flexibility)
Sylics has developed a four-night automated CognitionWall™ test to efficiently identify reversal learning impairments in mice (Remmelink et al. 2016). 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.
8 Arm Radial Maze
The eight‐arm radial maze evaluates spatial working memory. This test consists of a central platform connected to eight enclosed arms, which each contain an invisible food reward at the end of the arm. This task requires mice to remember whether an arm has already been visited and therefore requires intact spatial working memory. The number of re-entry errors into previously visited arms is a measure of spatial working memory. Mouse models of Alzheimer’s disease display impaired learning in the 8-arm radial maze compared with wild-type littermates.
Barnes Maze
The Barnes Maze is a test for spatial learning and memory. The test contains 24 holes and mice need to learn to locate the escape hole using the visual cues around the maze. This is followed up by a reversal trial, which measures the acquisition of new a new memory. As also detected in cancer patients, chemotherapy in mice is associated with changes in cognition. Administration of several cytotoxic chemotherapies was shown to lead to impaired performance in the Barnes Maze (Seigers et al 2015). The Stxbp1 mouse model is impaired in the reversal learning protocol of this task (Kovacevic et al. 2018)
Contextual Fear Conditioning
Fear conditioning is a widely used test that measures aversive memory. In contextual fear conditioning, mice learn to pair an unconditioned stimulus with an aversive context. The so-called freezing response of the mouse is monitored to assess the extent to which the unconditioned stimulus is paired with the context. This test is both a measure of anxiety and cognition (learning and memory).
Morris Water Maze
The Morris Water Maze (MWM) is a widely used test for assessing spatial learning and memory. In the MWM, mice need to learn the location of a submerged platform in a circular water pool using the visual cues around the maze. It is the standard test for detecting cognitive impairment in mouse models for Alzheimer’s disease, mutagenesis studies of neural plasticity-related genes and other impairments of long-term spatial memory. We routinely test mouse models of Alzheimer’s disease in the MWM, which show deficits in memorizing the platform location.
Nesting Test
Both male and female mice will build a nest when they are provided with suitable building material. Nest building requires organization of a complex set of behaviors, and is highly sensitive to interventions that affect hippocampal function. To assess nest building behavior, additional nesting material is introduced into each animal’s home-cage. The next morning, nest quality is scored on a scale from 1-5. Nest building is affected in mouse models of Alzheimer's disease, which is likely to be the result of hippocampal deficits.
Novel Object Recognition
The novel object recognition (NOR) test is used to test the memory for the shape, size, and location of objects. It capitalizes on the preference of mice for novelty, as this test measures how long the mouse interacts with a novel object. For the mouse to identify an object as novel, it has to remember that it has seen the object before. The novel object recognition test is therefore used as test of memory function. NOR is impaired in mouse models of Alzheimer's disease. In addition, we previously reported an impaired novel object memory performance in SNAP-25 heterozygous knockout mice, which is a risk gene for ADHD (Corradini et al 2014)
T Maze Spontaneous Alternation
Short-term spatial memory can be assessed in a T-maze. During a sample trial, the mouse is placed in the base of the “T” to explore the maze. After an entry into one other arm, it is contained in this arm for 30 seconds by lowering a guillotine door at the entrance of the arm. During the test trial, the mouse is placed back into the start arm. A successful alternation is scored if the mouse chooses to enter the previously non-visited arm, indicating that it remembered which arm it visited before. Mouse models of Alzheimer’s disease show deficits in T-maze performance, which is likely to be the result of hippocampal deficits.
Loos et al. (2014) Cereb Cortex
Epileptiform activity and cognitive deficits in SNAP-25(+/-) mice are normalized by antiepileptic drugs. Corradini, Loos et al., Cereb Cortex. 2014; 24:364, PMID: 23064108
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. https://pubmed.ncbi.nlm.nih.gov/24894481/
Loos et al (2014) Biol Psychiatry
Neuregulin-3 in the mouse medial prefrontal cortex regulates impulsive action. Loos M, Mueller T, Gouwenberg Y, Wijnands R, van der Loo RJ; Neuro-BSIK Mouse Phenomics Consortium, Birchmeier C, Smit AB, Spijker S. Biol Psychiatry. 2014 Oct 15;76(8):648-55. doi: 10.1016/j.biopsych.2014.02.011. Epub 2014 Feb 24. PMID: 24703509. https://pubmed.ncbi.nlm.nih.gov/24703509/
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. https://pubmed.ncbi.nlm.nih.gov/24312033/
Loos et al. (2013) Front Behav Neurosci
Loos M, Staal J, Smit AB, De Vries TJ, Spijker S. Enhanced alcohol self-administration and reinstatement in a highly impulsive, inattentive recombinant inbred mouse strain. Front Behav Neurosci. 2013 Oct 30;7:151. doi: 10.3389/fnbeh.2013.00151. PMID: 24198771; PMCID: PMC3812782. https://pubmed.ncbi.nlm.nih.gov/24198771/
Keywords: Addiction, alcohol, psychiatry
Maroteaux et al. (2012) Genes Brain Behav
High-throughput phenotyping of avoidance learning in mice discriminates different genotypes and identifies a novel gene. Maroteaux G, Loos M, van der Sluis S, Koopmans B, Aarts E, van Gassen K, Geurts A; NeuroBSIK Mouse Phenomics Consortium, Largaespada DA, Spruijt BM, Stiedl O, Smit AB, Verhage M. Genes Brain Behav. 2012 Oct;11(7):772-84. doi: 10.1111/j.1601-183X.2012.00820.x. Epub 2012 Aug 2. PMID: 22846151; PMCID: PMC3508728. https://pubmed.ncbi.nlm.nih.gov/22846151/
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. https://pubmed.ncbi.nlm.nih.gov/22098762/
Guillem et al. (2011) Science
Nicotinic acetylcholine receptor β2 subunits in the medial prefrontal cortex control attention. Guillem K, Bloem B, Poorthuis RB, Loos M, Smit AB, Maskos U, Spijker S, Mansvelder HD. Science. 2011 Aug 12;333(6044):888-91. doi: 10.1126/science.1207079. PMID: 21836018. https://pubmed.ncbi.nlm.nih.gov/21836018/
Counotte et al (2011) Nat Neurosci
Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Counotte DS, Goriounova NA, Li KW, Loos M, van der Schors RC, Schetters D, Schoffelmeer AN, Smit AB, Mansvelder HD, Pattij T, Spijker S. Nat Neurosci. 2011 Apr;14(4):417-9. doi: 10.1038/nn.2770. Epub 2011 Feb 20. PMID: 21336271. https://pubmed.ncbi.nlm.nih.gov/21336271/
Loos et al. (2010) Behav Brain Res
Inhibitory control and response latency differences between C57BL/6J and DBA/2J mice in a Go/No-Go and 5-choice serial reaction time task and strain-specific responsivity to amphetamine. Loos M, Staal J, Schoffelmeer AN, Smit AB, Spijker S, Pattij T. Behav Brain Res. 2010 Dec 25;214(2):216-24. doi: 10.1016/j.bbr.2010.05.027. Epub 2010 May 24. PMID: 20580749. https://pubmed.ncbi.nlm.nih.gov/20580749/
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