MouseBytes, an open-access high-throughput pipeline and database for rodent touchscreen-based cognitive assessment

Open Science has changed research by making data accessible and shareable, contributing to replicability to accelerate and disseminate knowledge. However, for rodent cognitive studies the availability of tools to share and disseminate data is scarce. Automated touchscreen-based tests enable systematic cognitive assessment with easily standardised outputs that can facilitate data dissemination. Here we present an integration of touchscreen cognitive testing with an open-access database public repository (mousebytes.ca), as well as a Web platform for knowledge dissemination (https://touchscreencognition.org). We complement these resources with the largest dataset of age-dependent high-level cognitive assessment of mouse models of Alzheimer’s disease, expanding knowledge of affected cognitive domains from male and female mice of three strains. We envision that these new platforms will enhance sharing of protocols, data availability and transparency, allowing meta-analysis and reuse of mouse cognitive data to increase the replicability/reproducibility of datasets.

[1]  Jorge Boucas,et al.  Integration of ENCODE RNAseq and eCLIP Data Sets. , 2018, Methods in molecular biology.

[2]  Ludwig Huber,et al.  Utilising dog-computer interactions to provide mental stimulation in dogs especially during ageing , 2017, ACI.

[3]  D. Couper,et al.  Iterative Outlier Removal: A Method for Identifying Outliers in Laboratory Recalibration Studies. , 2016, Clinical chemistry.

[4]  L. Saksida,et al.  Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses , 2019, Molecular Brain.

[5]  Mahabubur Rahman,et al.  Online molecular image repository and analysis system: A multicenter collaborative open-source infrastructure for molecular imaging research and application , 2018, Comput. Biol. Medicine.

[6]  D. Barros,et al.  Regulation of Cognitive Processing by Hippocampal Cholinergic Tone , 2016, Cerebral cortex.

[7]  Kenneth J. Leising,et al.  Need to train your rat? There is an App for that: A touchscreen behavioral evaluation system , 2013, Behavior Research Methods.

[8]  S. Baron-Cohen,et al.  Neuroscience and Biobehavioral Reviews a Meta-analysis of Sex Differences in Human Brain Structure , 2022 .

[9]  John F. Cryan,et al.  A low-cost touchscreen operant chamber using a Raspberry Pi™ , 2018, Behavior Research Methods.

[10]  Robert W. Williams,et al.  Reproducibility and replicability of rodent phenotyping in preclinical studies , 2016, Neuroscience & Biobehavioral Reviews.

[11]  Leanne Stevens,et al.  Reference and working memory deficits in the 3xTg-AD mouse between 2 and 15-months of age: A cross-sectional study , 2015, Behavioural Brain Research.

[12]  Douglas Wahlsten,et al.  Different data from different labs: lessons from studies of gene-environment interaction. , 2003, Journal of neurobiology.

[13]  D. Sherry,et al.  Sex Differences in Spatial Memory in Brown-Headed Cowbirds: Males Outperform Females on a Touchscreen Task , 2015, PloS one.

[14]  Krzysztof J. Gorgolewski,et al.  Making big data open: data sharing in neuroimaging , 2014, Nature Neuroscience.

[15]  Lina Zeldovich Genetic drift: the ghost in the genome , 2017, Lab animal.

[16]  M. Tsai,et al.  Progesterone and estrogen , 1993 .

[17]  H. Braak,et al.  The Biphasic Relationship between Regional Brain Senile Plaque and Neurofibrillary Tangle Distributions: Modification by Age, Sex, and APOE Polymorphism , 2004, Annals of the New York Academy of Sciences.

[18]  D. Gaffan,et al.  Impaired Recency Judgments and Intact Novelty Judgments after Fornix Transection in Monkeys , 2004, The Journal of Neuroscience.

[19]  L. Montoliu,et al.  A simple polymerase chain reaction assay for genotyping the retinal degeneration mutation (Pdebrd1) in FVB/N-derived transgenic mice , 2001, Laboratory animals.

[20]  M. Mattson,et al.  Triple-Transgenic Model of Alzheimer's Disease with Plaques and Tangles Intracellular Aβ and Synaptic Dysfunction , 2003, Neuron.

[21]  Emma L. Burrows,et al.  Evaluation of attention in APP/PS1 mice shows impulsive and compulsive behaviours , 2019, Genes, brain, and behavior.

[22]  Tsuyoshi Koide,et al.  Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice , 2017, Scientific Reports.

[23]  L. Saksida,et al.  A Touchscreen Motivation Assessment Evaluated in Huntington's Disease Patients and R6/1 Model Mice , 2019, Front. Neurol..

[24]  Joanna L. Jankowsky,et al.  Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase , 2004 .

[25]  L. Saksida,et al.  The touchscreen cognitive testing method for rodents: how to get the best out of your rat. , 2008, Learning & memory.

[26]  D. Diamond,et al.  Behavioral assessment of Alzheimer's transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory. , 2001, DNA and cell biology.

[27]  Anita Burgun-Parenthoine,et al.  Exploring and visualizing multidimensional data in translational research platforms , 2016, Briefings Bioinform..

[28]  Frank Z. Stanczyk,et al.  Sex differences in β-amyloid accumulation in 3xTg-AD mice: Role of neonatal sex steroid hormone exposure , 2010, Brain Research.

[29]  Ludwig Huber,et al.  The Vienna comparative cognition technology (VCCT): An innovative operant conditioning system for various species and experimental procedures , 2012, Behavior research methods.

[30]  M. Ohno,et al.  Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation , 2006, The Journal of Neuroscience.

[31]  K. Duff,et al.  Behavioral Changes in Transgenic Mice Expressing Both Amyloid Precursor Protein and Presenilin-1 Mutations: Lack of Association with Amyloid Deposits , 1999, Behavior genetics.

[32]  J. D. McGaugh,et al.  Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice , 2007, Neurobiology of Disease.

[33]  Self-Concept Variables Sex Differences in , 2016 .

[34]  Vanessa Schmitt,et al.  Implementing new portable touchscreen-setups to enhance cognitive research and enrich zoo-housed animals , 2018, bioRxiv.

[35]  M. Laine,et al.  Applicability of the CANTAB-PAL Computerized Memory Test in Identifying Amnestic Mild Cognitive Impairment and Alzheimer’s Disease , 2012, Dementia and Geriatric Cognitive Disorders.

[36]  J. Haxby,et al.  Sustained Attention in Mild Alzheimer's Disease , 2005, Developmental neuropsychology.

[37]  Frank Z. Stanczyk,et al.  Progesterone and Estrogen Regulate Alzheimer-Like Neuropathology in Female 3xTg-AD Mice , 2007, The Journal of Neuroscience.

[38]  B. Sahakian,et al.  The Effects of Nicotine on Attention, Information Processing, and Short-Term Memory in Patients with Dementia of the Alzheimer Type , 1989, British Journal of Psychiatry.

[39]  A. Kaddoumi,et al.  Effect of mouse strain as a background for Alzheimer's disease models on the clearance of amyloid-β. , 2016, Journal of systems and integrative neuroscience.

[40]  J. Crabbe,et al.  Genetics of mouse behavior: interactions with laboratory environment. , 1999, Science.

[41]  Louise D McCullough,et al.  NIH initiative to balance sex of animals in preclinical studies: generative questions to guide policy, implementation, and metrics , 2014, Biology of Sex Differences.

[42]  N. Lavine,et al.  The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to beta-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment , 2017 .

[43]  Abraham A. Palmer,et al.  Genetic Background Limits Generalizability of Genotype-Phenotype Relationships , 2016, Neuron.

[44]  Steven Williams,et al.  Applying Dataflow Architecture and Visualization Tools to In Vitro Pharmacology Data Automation , 2016, Journal of laboratory automation.

[45]  Brian A. Nosek,et al.  Power failure: why small sample size undermines the reliability of neuroscience , 2013, Nature Reviews Neuroscience.

[46]  B. Kolisnyk,et al.  α7 nicotinic ACh receptor‐deficient mice exhibit sustained attention impairments that are reversed by β2 nicotinic ACh receptor activation , 2015, British journal of pharmacology.

[47]  Andrew D. Johnson,et al.  Bmc Medical Genetics an Open Access Database of Genome-wide Association Results , 2009 .

[48]  R. Bartha,et al.  Forebrain Deletion of the Vesicular Acetylcholine Transporter Results in Deficits in Executive Function, Metabolic, and RNA Splicing Abnormalities in the Prefrontal Cortex , 2013, The Journal of Neuroscience.

[49]  Jack Bergman,et al.  A novel touch-sensitive apparatus for behavioral studies in unrestrained squirrel monkeys , 2012, Journal of Neuroscience Methods.

[50]  Lisa M. Saksida,et al.  A touch screen-automated cognitive test battery reveals impaired attention, memory abnormalities, and increased response inhibition in the TgCRND8 mouse model of Alzheimer's disease , 2013, Neurobiology of Aging.

[51]  Lisa M Saksida,et al.  The touchscreen operant platform for testing working memory and pattern separation in rats and mice , 2013, Nature Protocols.

[52]  L. Saksida,et al.  Impaired Attention in the 3xTgAD Mouse Model of Alzheimer's Disease: Rescue by Donepezil (Aricept) , 2011, The Journal of Neuroscience.

[53]  Adam G Diehl,et al.  Deciphering ENCODE. , 2016, Trends in genetics : TIG.

[54]  D. Borchelt,et al.  Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. , 2004, Human molecular genetics.

[55]  M. Block,et al.  Retinoic Acid Attenuates β-Amyloid Deposition and Rescues Memory Deficits in an Alzheimer's Disease Transgenic Mouse Model , 2008, The Journal of Neuroscience.

[56]  L. Saksida,et al.  A computer-automated touchscreen paired-associates learning (PAL) task for mice: impairments following administration of scopolamine or dicyclomine and improvements following donepezil , 2011, Psychopharmacology.

[57]  Brianne A. Kent,et al.  Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome , 2016, Cerebral cortex.

[58]  L. Saksida,et al.  Optimizing reproducibility of operant testing through reinforcer standardization: identification of key nutritional constituents determining reward strength in touchscreens , 2017, Molecular Brain.

[59]  Christian Windischberger,et al.  Toward discovery science of human brain function , 2010, Proceedings of the National Academy of Sciences.

[60]  Carol J. Bult,et al.  Mouse Phenome Database , 2013, Nucleic Acids Res..

[61]  Richard E. Tremblay,et al.  KmL3D: A non-parametric algorithm for clustering joint trajectories , 2013, Comput. Methods Programs Biomed..

[62]  T. Reyes,et al.  Let’s call the whole thing off: evaluating gender and sex differences in executive function , 2018, Neuropsychopharmacology.

[63]  Brianne A. Kent,et al.  The touchscreen operant platform for assessing executive function in rats and mice , 2013, Nature Protocols.

[64]  Elissa J. Chesler,et al.  Influences of laboratory environment on behavior , 2002, Nature Neuroscience.

[65]  Gautier Koscielny,et al.  The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data , 2013, Nucleic Acids Res..

[66]  Talal S Masood,et al.  Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1) , 2015, Disease Models & Mechanisms.

[67]  Timothy J Bussey,et al.  The touchscreen operant platform for testing learning and memory in rats and mice , 2013, Nature Protocols.

[68]  D. Clair,et al.  Bridging the translational divide: identical cognitive touchscreen testing in mice and humans carrying mutations in a disease-relevant homologous gene , 2015, Scientific Reports.

[69]  L. Saksida,et al.  Paying more attention to attention: Towards more comprehensive cognitive translation using mouse models of Alzheimer's disease , 2013, Brain Research Bulletin.

[70]  Mark Gerstein,et al.  Genomics: ENCODE leads the way on big data , 2012, Nature.

[71]  Tarak Driss,et al.  kmlShape: An Efficient Method to Cluster Longitudinal Data (Time-Series) According to Their Shapes , 2016, PloS one.

[72]  J. Hodges,et al.  The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer’s disease: relationship to episodic and semantic memory impairment , 2000, Neuropsychologia.

[73]  M. Macleod,et al.  From a mouse: systematic analysis reveals limitations of experiments testing interventions in Alzheimer's disease mouse models , 2016, Evidence-based preclinical medicine.

[74]  Jesse S. Rodriguez,et al.  CANTAB delayed matching to sample task performance in juvenile baboons , 2011, Journal of Neuroscience Methods.

[75]  Mark H. Tuszynski,et al.  Age-related cognitive deficits in rhesus monkeys mirror human deficits on an automated test battery , 2010, Neurobiology of Aging.

[76]  Andrew D. Blackwell,et al.  Detecting Dementia: Novel Neuropsychological Markers of Preclinical Alzheimer’s Disease , 2003, Dementia and Geriatric Cognitive Disorders.

[77]  Oskar Pineño ArduiPod Box: A low-cost and open-source Skinner box using an iPod Touch and an Arduino microcontroller , 2014, Behavior research methods.

[78]  J. Roder,et al.  NIH Swiss and Black Swiss mice have retinal degeneration and performance deficits in cognitive tests. , 2005, Comparative medicine.

[79]  Jung-Eun Lee,et al.  An Update of Animal Models of Alzheimer Disease with a Reevaluation of Plaque Depositions , 2013, Experimental neurobiology.

[80]  Robert W. Williams,et al.  Strains and Stressors: An Analysis of Touchscreen Learning in Genetically Diverse Mouse Strains , 2014, PloS one.