An Automated, Experimenter-Free Method for the Standardised, Operant Cognitive Testing of Rats

Animal models of human pathology are essential for biomedical research. However, a recurring issue in the use of animal models is the poor reproducibility of behavioural and physiological findings within and between laboratories. The most critical factor influencing this issue remains the experimenter themselves. One solution is the use of procedures devoid of human intervention. We present a novel approach to experimenter-free testing cognitive abilities in rats, by combining undisturbed group housing with automated, standardized and individual operant testing. This experimenter-free system consisted of an automated-operant system (Bussey-Saksida rat touch screen) connected to a home cage containing group living rats via an automated animal sorter (PhenoSys). The automated animal sorter, which is based on radio-frequency identification (RFID) technology, functioned as a mechanical replacement of the experimenter. Rats learnt to regularly and individually enter the operant chamber and remained there for the duration of the experimental session only. Self-motivated rats acquired the complex touch screen task of trial-unique non-matching to location (TUNL) in half the time reported for animals that were manually placed into the operant chamber. Rat performance was similar between the two groups within our laboratory, and comparable to previously published results obtained elsewhere. This reproducibility, both within and between laboratories, confirms the validity of this approach. In addition, automation reduced daily experimental time by 80%, eliminated animal handling, and reduced equipment cost. This automated, experimenter-free setup is a promising tool of great potential for testing a large variety of functions with full automation in future studies.

[1]  A. Ramos,et al.  Common variations in the pretest environment influence genotypic comparisons in models of anxiety , 2005, Genes, brain, and behavior.

[2]  T R Zentall,et al.  Observational Learning and Social Facilitation in the Rat , 1972, Science.

[3]  Andrea T. U. Schaefers,et al.  Rapid task acquisition of spatial-delayed alternation in an automated T-maze by mice , 2011, Behavioural Brain Research.

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

[5]  Kelly Gouveia,et al.  Reducing Mouse Anxiety during Handling: Effect of Experience with Handling Tunnels , 2013, PloS one.

[6]  L. Toth,et al.  The influence of the cage environment on rodent physiology and behavior: Implications for reproducibility of pre-clinical rodent research , 2015, Experimental Neurology.

[7]  O. Riess,et al.  Automated phenotyping and advanced data mining exemplified in rats transgenic for Huntington's disease , 2014, Journal of Neuroscience Methods.

[8]  L. Saksida,et al.  Dissociation between memory retention across a delay and pattern separation following medial prefrontal cortex lesions in the touchscreen TUNL task , 2013, Neurobiology of Learning and Memory.

[9]  T. Steckler,et al.  Strain-dependent effects on acquisition and reversal of visual and spatial tasks in a rat touchscreen battery of cognition , 2015, Physiology & Behavior.

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

[11]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[12]  T. Robbins,et al.  Measuring the construct of executive control in schizophrenia: Defining and validating translational animal paradigms for discovery research , 2013, Neuroscience & Biobehavioral Reviews.

[13]  L. Saksida,et al.  New translational assays for preclinical modelling of cognition in schizophrenia: The touchscreen testing method for mice and rats , 2012, Neuropharmacology.

[14]  A. Smit,et al.  Measuring discrimination- and reversal learning in mouse models within 4 days and without prior food deprivation , 2016, Learning & memory.

[15]  J. Hurst,et al.  Taming anxiety in laboratory mice , 2010, Nature Methods.

[16]  T. Werka,et al.  Social modulation in extinction of aversive memories , 2013, Behavioural Brain Research.

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

[18]  Andrea T. U. Schaefers,et al.  A sorting system with automated gates permits individual operant experiments with mice from a social home cage , 2011, Journal of Neuroscience Methods.

[19]  R. Picetti,et al.  Effects of handling and vehicle injections on adrenocorticotropic and corticosterone concentrations in Sprague-Dawley compared with Lewis rats. , 2015, Journal of the American Association for Laboratory Animal Science : JAALAS.

[20]  A. Young,et al.  A comparison between Dark Agouti and Sprague-Dawley rats in their behaviour on the elevated plus-maze, open-field apparatus and activity meters, and their response to diazepam , 2002, Psychopharmacology.

[21]  Ariane Santoso,et al.  Individually dosed oral drug administration to socially-living transponder-tagged mice by a water dispenser under RFID control , 2006, Journal of Neuroscience Methods.

[22]  K Safi,et al.  Consistent behavioral phenotype differences between inbred mouse strains in the IntelliCage , 2010, Genes, brain, and behavior.

[23]  J. Haller,et al.  Glucocorticoid Hyper‐ and Hypofunction , 2007, Annals of the New York Academy of Sciences.

[24]  J. Homberg,et al.  Cross-species approaches to pathological gambling: A review targeting sex differences, adolescent vulnerability and ecological validity of research tools , 2013, Neuroscience & Biobehavioral Reviews.

[25]  L. Saksida,et al.  Trial-unique, delayed nonmatching-to-location (TUNL): A novel, highly hippocampus-dependent automated touchscreen test of location memory and pattern separation , 2010, Neurobiology of Learning and Memory.

[26]  J. Bohacek,et al.  Increased daily handling of ovariectomized rats enhances performance on a radial-maze task and obscures effects of estradiol replacement , 2007, Hormones and Behavior.

[27]  Loren J. Martin,et al.  Olfactory exposure to males, including men, causes stress and related analgesia in rodents , 2014, Nature Methods.