Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction

Abstract

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopperswitching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be controlled by one computer. Video LinkThe video component of this article can be found at http://www.jove.com/video/51047/ IntroductionTo bring the powerful techniques of genetics, molecular genetics, molecular biology, and neuropharmacology to bear on elucidating the cellular and molecular mechanisms that mediate basic mechanisms of cognition, we need high-volume, high-through-put psychophysical screening methods that quantify physiologically meaningful properties of cognitive mechanisms. A psychophysically measurable, physiological meaningful quantitative property of a mechanism is a property that can be measured by behavioral means and also by electrophysiological or biochemical means. Examples are the absorption spectrum of rhodopsin, the free-running period of the circadian clock, and the refractory period of reward axons in the medial forebrain bundle 1,2 . Psychophysical measurements that can be compared to cellular and molecular measurements lay a foundation for linking cellular and molecular mechanisms to psychological mechanisms through q...

High-Throughput Automatic Training System for Odor-Based Learned Behaviors in Head-Fixed Mice

“…With feedback controlling components, automatic training systems have been successfully implemented in multiple behavioral domains, including memory assessment (Reiss et al, 2014 ), operant learning (Remmelink et al, 2015 ), and training limb function (Becker et al, 2016 ). Automatic training systems with multiple cognitive behaviors requiring memory, attention and decision making have been developed previously in free-moving rats (Erlich et al, 2011 ; Poddar et al, 2013 ) and mice (Romberg et al, 2013 ; Gallistel et al, 2014 ; Burgess et al, 2017 ). Moreover, such systems were successful in dissecting neural-circuitry mechanisms underlying cognitive behaviors (e.g., Erlich et al, 2011 ; Brunton et al, 2013 ; Hanks et al, 2015 ).…”

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“…Autoshaping memory tasks have been focus by several research groups (e.g., Brown and Jenkins, 1968 ; Myer and Hull, 1974 ; Atnip, 1977 ; Oscos et al, 1988 ; Bussey et al, 1997 , 2013 ; Lindner et al, 2003 ; Vanover et al, 2004 ; Ballaz et al, 2007 ; Rodriguez et al, 2008 ; Walker and Foley, 2010 ; Walker et al, 2011 ; Tomie et al, 2012 ; Krynetskiy et al, 2013 ; Markou et al, 2013 ; Gallistel et al, 2014 ; Holland et al, 2014 ; Lesaint et al, 2014 ; Talpos et al, 2014 ; Eskenazi et al, 2015 ; Talpos and Shoaib, 2015 ; in several animal species (e.g., Wasserman, 1981 ) including humans (Wilcove and Miller, 1974 ; Pithers, 1985 ). According with Holland et al ( 2014 ), “autoshaping” or “sign-tracking” phenomenon has recently attracted considerable attention as a platform for studying individual differences in impulsivity, drug sensitization, and other traits associated with vulnerability to drug addiction.…”

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“…The testing system is described in detail in [9]. Briefly, the mice lived individually in test environments each consisting of a standard polypropylene nest tub connected via a short acrylic tube to a MedAssociates mouse test chamber with three hoppers along the far wall (figure 1).…”