Name: automated, quantitative cognitive/behavioral screening of mice: for genetics, pharmacology, animal cognition and undergraduate instruction
Uploaded: 2014-02-26T22:00:00
Description: Watch this Scientific Journal Video about Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction at JoVE.com

The creation of this system was supported by 5RO1MH77027.

The three fully automated protocols in the TSsystem (matching, appetitive instrumental and classical conditioning) and the switch protocol have been approved by the Animal Care and Facilities Committee at Rutgers New Brunswick.
1. Setting Up the Physical System
<ol>
	<li>Set up the test environments in the cabinets (see Figure 1).</li>
	<li>Install the experiment-control software provided with the test environments on the protocol-control computers. 
	Note:</str...

<ol>
	<li>Gallistel, C. R., Shizgal, P., Yeomans, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+portrait+of+the+substrate+for+self-stimulation.">A portrait of the substrate for self-stimulation.</a> Psychol. Rev. 88, 228-273 (1981).</li><li>Takahashi, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+neurobiology+and+genetics+of+circadian+rhythms+in+mammals.">Molecular neurobiology and genetics of circadian rhythms in mammals.</a> Ann. Rev. Neurosci. 18, 531-553 (1995).</li><li>Mackay, T. F. C., Stone, E. A., Ayroles, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+genetics+of+quantitative+traits:+challenges+and+prospects.">The genetics of quantitative traits: challenges and prospects.</a> 10, 565-577 (2009).</li><li>Weber, J. N., Peterson, B. K., Hoekstra, H. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Discrete+genetic+modules+are+responsible+for+complex+burrow+evolution+in+Peromyscus+mice.">Discrete genetic modules are responsible for complex burrow evolution in Peromyscus mice.</a> Nature. 493, 402-405 (2013).</li><li>Balsam, P. D., Drew, M. R., Gallistel, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time+and+Associative+Learning.">Time and Associative Learning.</a> Compar. Cogn. Behav. Rev. 5, 1-22 (2010).</li><li>Gallistel, C. R., Gibbon, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Psychol+Rev.">Psychol Rev.</a> Psychol Rev. 107, 289-344 (2000).</li><li>Ward, R. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conditional+Stimulus+Informativeness+Governs+Conditioned+Stimulus&#8212;Unconditioned+Stimulus+Associability.">Conditional Stimulus Informativeness Governs Conditioned Stimulus&#8212;Unconditioned Stimulus Associability.</a> J. Exp. Psychol. Animal Behav. Process. 38, 217-232 (2012).</li><li>Gallistel, C. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Is+matching+innate.">Is matching innate.</a> J. Exp. Anal. Behav. 87, 161-199 (2007).</li><li>Herrnstein, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Derivatives+of+matching.">Derivatives of matching.</a> Psychol. Rev. 86, 486-495 (1979).</li><li>Mark, T. A., Gallistel, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinetics+of+matching.">Kinetics of matching.</a> J. Exp. Psychol. Animal Behav. Process. 20, 79-95 (1994).</li><li>Brandeis, R., Brandys, Y., Yehuda, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+the+Morris+water+maze+in+the+study+of+memory+and+learning.">The use of the Morris water maze in the study of memory and learning.</a> Int. J. Neurosci. 48, 29-69 (1989).</li><li>Foucaud, J., Burns, J. G., Mery, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+spatial+information+and+search+strategies+in+a+water+maze+analog+in+Drosophila+melanogaster.">Use of spatial information and search strategies in a water maze analog in Drosophila melanogaster.</a> PLoS ONE. 5, (2010).</li><li>Logue, S. F., Paylor, R., Wehner, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hippocampal+lesions+cause+learning+deficits+in+inbred+mice+in+the+Morris+water+maze+and+conditioned-fear+task.">Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task.</a> Behav. Neurosci. 111, 104-113 (1997).</li><li>Upchurch, M., Wehner, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+between+inbred+strains+of+mice+in+Morris+water+maze+performance.">Differences between inbred strains of mice in Morris water maze performance.</a> Behav. Genet. 18, 55-68 (1988).</li><li>Zilles, K., Wu, J., Crusio, W. E., Schwegler, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Water+maze+and+radial+maze+learning+and+the+density+of+binding+sites+of+glutamate,+GABA,+and+serotonin+receptors+in+the+hippocampus+of+inbred+mouse+strains.">Water maze and radial maze learning and the density of binding sites of glutamate, GABA, and serotonin receptors in the hippocampus of inbred mouse strains.</a> Hippocampus. 10, 213-225 (2000).</li><li>Chen, G., King, J. A., Burgess, N., O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+vision+and+movement+combine+in+the+hippocampal+place+code.">How vision and movement combine in the hippocampal place code.</a> Proc. Natl. Acad. Sci. U.S.A. 110, 378-383 (2013).</li><li>Gallistel, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The organization of learning. , (1990).</li><li>Wittlinger, M., Wehner, R., Wolf, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+desert+ant+odometer:+a+stride+integrator+that+accounts+for+stride+length+and+walking+speed.">The desert ant odometer: a stride integrator that accounts for stride length and walking speed.</a> J. Exp. Biol. 210, (2007).</li><li>Challet, E., Mendoza, J., Dardente, H., Pevet, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurogenetics+of+food+anticipation.">Neurogenetics of food anticipation.</a> Eur. J. Neurosci. 30, 1676-1687 (2009).</li><li>Arcediano, F., Miller, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Some+constraints+for+models+of+timing:+A+temporal+coding+hypothesis+perspective.">Some constraints for models of timing: A temporal coding hypothesis perspective.</a> Learn. Mot. 33, 105-123 (2002).</li><li>Denniston, J. C., Blaisdell, A. P., Miller, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temporal+Coding+in+Conditioned+Inhibition:+Analysis+of+Associative+Structure+of+Inhibition.">Temporal Coding in Conditioned Inhibition: Analysis of Associative Structure of Inhibition.</a> J. Exp. Psychol. Animal Behav. Process. 30, 190-202 (2004).</li><li>Balci, F., Freestone, D., Gallistel, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+assessment+in+man+and+mouse.">Risk assessment in man and mouse.</a> Proc. Natl. Acad. Sci. U.S.A. 106, 2459-2463 (2009).</li><li>Kheifets, A., Gallistel, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mice+take+calculated+risks.">Mice take calculated risks.</a> Proc. Natl. Acad. Sci. U.S.A. 109, 8776-8779 (2012).</li><li>Fetterman, J. G., Killeen, P. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Categorical+scaling+of+time:+Implications+for+clock-counter+models.">Categorical scaling of time: Implications for clock-counter models.</a> J. Exp. Psychol. Animal Behav. Process. 21, 43-63 (1995).</li><li>Luby, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Food+anticipatory+activity+behavior+of+mice+across+a+wide+range+of+circadian+and+non-circadian+intervals.">Food anticipatory activity behavior of mice across a wide range of circadian and non-circadian intervals.</a> PLoS One. 7, (2012).</li><li>Lee, S. A., Vallortigara, G., Ruga, V., Sovrano, V. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Independent+effects+of+geometry+and+landmark+in+a+spontaneous+reorientation+task:+a+study+of+two+species+of+fish.">Independent effects of geometry and landmark in a spontaneous reorientation task: a study of two species of fish.</a> Animal Cogn. 15, 861-870 (2012).</li><li>Rodriguiz, R., Wetsel, W. C., Levin, E. D., Buccafusco, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Animal Models of Cognitive Impairment Ch. 12. , (2006).</li><li>Gallistel, C. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fully+Automated+Cognitive+Assessment+of+Mice+Strains+Heterozygous+for+Cell--Adhesion+Genes+Reveals+Strain--Specific+Alterations+in+Timing+Precision.">Fully Automated Cognitive Assessment of Mice Strains Heterozygous for Cell--Adhesion Genes Reveals Strain--Specific Alterations in Timing Precision.</a> Philosoph. Trans. Royal Soc. B. , (2013).</li></ol>

Our method yields a wide range of physiological meaningful, quantitative results on the functioning of several different mechanisms of cognition, learning and memory, for many mice at once, in a minimum amount of time, with a minimum of human labor, and with no handling of the experimental subjects during days, weeks, or months of testing. These attributes suit it for genetic and pharmacological screening programs. It uses minimally modified off-the-shelf hardware (test boxes and nest tubs). It produces more data from mo...

To 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 bundle1,2. Psychophysical measurements that can be compared to cellular and molecular measurements lay a foundation for linking cellular and molecular mechanisms to psychological mechanisms through quantitative correspondence. For example, the fact that the in situ absorption spectrum of the rhodopsin in the outer segments of rods superimposes on the human scotopic spectral sensitivity function is strong evidence that the photon-triggered isomerization of rhodopsin is the first step in scotopic vision. The quantitative aspects of complex behavior patterns are also central to the use of QTL methods in behavioral genetics3,4.
The performance of mice (and rats) on well-established instrumental and Pavlovian learning protocols depends on brain mechanisms that measure abstract quantities like time, number, duration, rate, probability, risk, and spatial location. For example, the speed of acquisition of Pavlovian conditioned responses depends on the ratio between the average interval between the reinforcing events (typically, food deliveries) and the average latency to reinforcement following the onset of the signal for impending reinforcement5-7. For a second example, the ratio of the average duration of the visits to two feeding hoppers in a matching protocol approximately equals the ratio of the rates of reinforcement at those two hoppers8-10.
The behavioral testing methods currently in wide use by neuroscientists interested in underlying mechanisms are, for the most part, low volume, low through-put, and labor intensive26. Moreover, they do not measure quantities that can be compared with quantities measured by electrophysiological and biochemical methods, as, for example, the behaviorally measured periods and phases of circadian oscillators may be compared to electrophysiological and biochemical measures of circadian period and phase. Current behavioral testing methods focus on categories of learning, such as spatial learning, temporal learning, or fear learning, rather than on underlying mechanisms. The widely used water maze test of spatial learning11-15 is an example of these shortcomings. Spatial learning is a category. Learning in that category depends on many mechanisms, one of which is the mechanism of dead reckoning16,17. Dead reckoning depends in turn on the odometer, the mechanism that measures distance run18. Similarly, temporal learning is a category. A circadian clock is among the mechanisms on which learning in that category depends, because an oscillator with an approximately 24&#160;hr period is required for animals to learn the time of day at which events occur17,19. The clock that enables food anticipation has yet to be discovered19.
A clock is a time-measuring mechanism. Endogenous oscillators with a wide range of periods allow the brain to locate events in time by recording the phases of those clocks16,17. The ability to record locations in time enables the measurement of durations, that is, distances between locations in time. Associative learning depends on the brain&#39;s measurements of durations5,6,20,21. Counters are number-measuring mechanisms. Number measuring enables probability estimation, because a probability is the proportion between the numerosity of a subset and the numerosity of the superset. Number measuring and duration measuring enable rate estimation, because a rate is the number of events divided by the duration of the interval over which that number was measured. Measurements of duration, number, rate, and probability enable behavioral adjustments to changing risks.22,23 Our method focuses on measuring the accuracy and precision of these foundational mechanisms. Accuracy is the extent to which the brain&#39;s measure corresponds to an objective measure. Precision is the variation or uncertainty in the brain&#39;s measure of a fixed objective value, for example, a fixed duration. Weber&#39;s Law is the oldest and most securely established result in psychophysics. It asserts that the precision of the brain&#39;s measure of a quantity is a fixed fraction of that quantity. The Weber Fraction, which is the statistician&#39;s coefficient of variation in a distribution (&#963;/&#956;), measures precision. The ratio of the psychophysical mean (e.g.&#160;mean judged duration) to the objective mean (mean objective duration) is the measure of accuracy.
The method presented here maximizes volume (number of animals being screened at any one time in a given amount of lab space) and throughput (amount of information obtained divided by the average duration of the screening of a single animal) while minimizing the amount of human labor required to make the measurements and maximizing the immediacy with which the results of the screening become known.
The data-analysis software architecture presented here automatically puts the raw data and all the summary results and statistics derived from the data together in a single data structure, with field headings that render intelligible the vast seas of numbers therein contained. The analytic software only operates on data in that structure, and always stores the results of its operations in fields within that same structure. This insures an intact trail from raw data to published summaries and graphs.
The software automatically writes into the structure the experiment-control programs that governed the fully automated testing, and it automatically indicates which raw data came from which program. Thus, it preserves an impeccable data trail, with no doubt as to which experimental conditions were in force for each animal at each point in the testing and no doubt about how the summary statistics were derived from the raw data. This method of data preservation greatly facilitates the development of standardized behavioral screening data bases, making it possible for other laboratories to further analyze these rich data sets.
This method minimizes the risk of loss of support for the firmware and software on which it depends. The testing apparatus is trivially modified from a long-established commercial source. The programming languages are the custom language provided by the hardware manufacturer, for protocol control, and, for data analysis and graphing, a purpose-built, noncommercial, open-source toolbox (TSsystem) written in a very widely supported commercial scientific programming, data analysis and graphing language. The toolbox contains high-level commands for extracting structural information and summary statistics from lengthy time-stamped event records. The protocol-implementing programs and the data-analyzing programs are open source and thoroughly documented.
The screening system is schematized in Figure 1. Ten cabinets, each containing 8 test environments may be set up in a 10 ft&#160;x 15 ft&#160;laboratory room, enabling 80 mice to be run at one time. Cables passing through a port in a party wall should connect the environments to the electronic/electrical interface cards and PCs in another room. The PCs run the protocol-control programs. One computer is required for every 2 cabinets (16 test environments). The PCs must be connected via a Local Area Network to a server running the data-analysis and graphing software.

<table border="0" cellpadding="0" cellspacing="0" width="881">>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">SmartCtrl Connection Panel</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">SG-716B (115)</td>
			<td style="width:339px;">control panel for inputs/outputs</td>
			<td style="width:67px;">8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">SmartCtrl Interface Module</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">DIG-716B (114)</td>
			<td>smart card for each chamber</td>
			<td>8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Universal Cable</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">SG-210CB (115)</td>
			<td>cable from smart card to control panel</td>
			<td>1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Tabletop Interface Cabinet</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">SG-6080C (109)</td>
			<td>cabinet to hold smart cards</td>
			<td>1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Rack Mount Power Supply</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">SG-500 (112)</td>
			<td>28 volt power</td>
			<td>1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Wide Mouse Test Chamber</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-307W (31)</td>
			<td>test chamber</td>
			<td>8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Filler Panel Package</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-307W-FP (32)</td>
			<td>various-size panels for test chamber</td>
			<td>8</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">Wide Mouse Modular Grid Floor</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-307W-GF (31)</td>
			<td>test chamber floor grid</td>
			<td>8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Head Entry Detector</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-303HDW (62)</td>
			<td>head entry/pellet entry into hopper</td>
			<td>40</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Pellet Dispenser</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-203-20 (73)</td>
			<td>feeder</td>
			<td>16</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Pellet Receptacle</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-303W (61)</td>
			<td>hopper</td>
			<td>24</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Pellet Receptacle Light</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-303RL (62)</td>
			<td>hopper light</td>
			<td>24</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">House Light</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-315W (43)</td>
			<td>house light</td>
			<td>8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">IR Controller</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-253B (77)</td>
			<td>entry detector for tube between nest and test</td>
			<td>16</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Fan</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;">ENV-025F28 (42)</td>
			<td>exhaust fan for each chamber</td>
			<td>8</td>
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		<tr height="21">
			<td height="21" style="height:21px;">Polypropylene Nest Tub</td>
			<td></td>
			<td></td>
			<td>nest box</td>
			<td>8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Acrylic Connection Tube</td>
			<td></td>
			<td></td>
			<td>connection between nest and test areas</td>
			<td>8</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Steel Cabinet</td>
			<td></td>
			<td></td>
			<td>cabinet to hold test chambers (78&#34;H, 48&#34;W, 24&#34;D)</td>
			<td>1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Windows computer</td>
			<td style="width:127px;"> </td>
			<td style="width:136px;"> </td>
			<td>running MedPC experiment-control software</td>
			<td>1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Server</td>
			<td style="width:127px;"> </td>
			<td style="width:136px;"> </td>
			<td>running Matlab, linked to exper-control computer by LAN</td>
			<td>1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;"> </td>
			<td style="width:127px;"> </td>
			<td style="width:136px;"> </td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Software</td>
			<td style="width:127px;"> </td>
			<td style="width:136px;"> </td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">MedPC software</td>
			<td style="width:127px;">Med Associates</td>
			<td style="width:136px;"> </td>
			<td>proprietary process-control programming language</td>
			<td>1</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Matlab w Statistics Toolbox</td>
			<td style="width:127px;">Matlab</td>
			<td style="width:136px;"> </td>
			<td>proprietary data analysis and graphing programing system</td>
			<td>1</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:213px;">TSsystem</td>
			<td></td>
			<td style="width:136px;">in Supplementary Material w updates from senior author</td>
			<td>Open-source Matlab Toolbox</td>
			<td>1</td>
		</tr>
		<tr height="189">
			<td height="189" style="height:189px;width:213px;">Note: This is the euipment needed for one cabinet, containing 8 test environments. Hardware must be replicated for each such cabinet. However one computer can control 2 cabinets (16 test environments)</td>
			<td style="width:127px;"> </td>
			<td style="width:136px;"> </td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

automated, quantitative cognitive/behavioral screening of mice: for genetics, pharmacology, animal cognition and undergraduate instruction

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 &#34;cloud&#34; 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 hopper-switching, 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&#160;cabinet; two such cabinets (16 environments) may be controlled by one computer.

The system can and should be used to run protocols tailored to the aims of the individual investigator or classroom teacher. However, we have developed a suite of 3 protocols that should prove useful in large-scale screening of genetically manipulated mice and large-scale pharmacological testing: the matching protocol, the 2-hopper autoshaping protocol, and the switch protocol. The matching protocol measures the mouse&#39;s capacity to estimate incomes (food pellets per unit time) at two different locations, to remember ...

Watch this Scientific Journal Video about Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction at JoVE.com

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

Fully automated system for measuring physiologically meaningful properties of the mechanisms mediating spatial localization, temporal localization, duration, rate&#160;and probability estimation, risk assessment, impulsivity, and the accuracy and precision of memory, in order to assess the effects of genetic and pharmacological manipulations on foundational mechanisms of cognition in mice.

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and ...

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