Name: a fully automated rodent conditioning protocol for sensorimotor integration and cognitive control experiments
Uploaded: 2014-04-15T18:00:00
Description: Watch this Scientific Journal Video about A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments at JoVE.com

This work was supported by the NINDS grant #NS054148.

All procedures involving animals were approved by the Michigan State University Institutional Animal Care and Use Committee (IACUC).
1. Experimental Setup
<ol>
	<li>Use an operant conditioning box which consists of a five-hole nosepoke wall on one side and a food delivery trough on the opposite side.
	<ol>
		<li>The center nosepoke hole is considered as a &#34;fixation&#34; hole and the four other holes (two on each side of the fixation hole) are considered motor target holes. Each hole is e...

<ol>
	<li>Goldstein, E. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Cognitive psychology: Connecting mind, research, and everyday experience. , (2008).</li><li>Kandel, E. R., Schwartz, J. H., Jessell, T. 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=4th+edition.">4th edition.</a> Principles of neural science. , (2000).</li><li>Cisek, P., Kalaska, 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=Neural+mechanisms+for+interacting+with+a+world+full+of+action+choices.">Neural mechanisms for interacting with a world full of action choices.</a> Ann. Rev. Neurosci. 33, 269-298 (2010).</li><li>Kalat, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Biological psychology. , (2012).</li><li>Banich, M. T., Compton, 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=.">.</a> Cognitive neuroscience. , (2010).</li><li>Carew, T. J., Pinsker, H. M., Kandel, E. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+habituation+of+a+defensive+withdrawal+reflex+in+aplysia.">Long-term habituation of a defensive withdrawal reflex in aplysia.</a> Science. 175, 451-454 (1972).</li><li>Hodgkin, A. L., Huxley, A. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+quantitative+description+of+membrane+current+and+its+application+to+conduction+and+excitation+in+nerve.">A quantitative description of membrane current and its application to conduction and excitation in nerve.</a> J. Physiol. 117, 500 (1952).</li><li>Romo, R., Salinas, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flutter+discrimination:+neural+codes,+perception,+memory+and+decision+making.">Flutter discrimination: neural codes, perception, memory and decision making.</a> Nat. Rev. Neurosci. 4, 203-218 (2003).</li><li>Romo, R., de Lafuente, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conversion+of+sensory+signals+into+perceptual+decisions.">Conversion of sensory signals into perceptual decisions.</a> Prog. Neurobiol. 10, (2012).</li><li>Shadlen, M. N., Britten, K. H., Newsome, W. T., Movshon, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+computational+analysis+of+the+relationship+between+neuronal+and+behavioral+responses+to+visual+motion.">A computational analysis of the relationship between neuronal and behavioral responses to visual motion.</a> J. Neurosci. 16, 1486-1510 (1996).</li><li>Beck, J. 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=Probabilistic+Population+Codes+for+Bayesian+Decision+Making.">Probabilistic Population Codes for Bayesian Decision Making.</a> Neuron. 60, 1142-1152 (2008).</li><li>Goldman-Rakic, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circuitry+of+primate+prefrontal+cortex+and+regulation+of+behavior+by+representational+memory.">Circuitry of primate prefrontal cortex and regulation of behavior by representational memory.</a> Compr. Physiol. , (1987).</li><li>Miller, E. K., Erickson, C. A., Desimone, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+mechanisms+of+visual+working+memory+in+prefrontal+cortex+of+the+macaque.">Neural mechanisms of visual working memory in prefrontal cortex of the macaque.</a> J. Neurosci. 16, 5154-5167 (1996).</li><li>Fuster, J. M., Alexander, G. E., 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=Neuron+activity+related+to+short-term+memory.">Neuron activity related to short-term memory.</a> Science. 173, 652-654 (1971).</li><li>Fetz, E. E., Baker, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Operantly Conditioned Patterns of Activity and Correlated Responses Cells and Contralateral Muscles. , (1973).</li><li>Carmena, J. 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=Learning+to+control+a+brain--machine+interface+for+reaching+and+grasping+by+primates.">Learning to control a brain--machine interface for reaching and grasping by primates.</a> PLoS Biol. 1, e42 (2003).</li><li>Georgopoulos, A. P., Schwartz, A. B., Kettner, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuronal+population+coding+of+movement+direction.">Neuronal population coding of movement direction.</a> Science. 233, 1416-1419 (1986).</li><li>Donoghue, J. P., Sanes, J. N., Hatsopoulos, N. G., Ga&#225;l, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+discharge+and+local+field+potential+oscillations+in+primate+motor+cortex+during+voluntary+movements.">Neural discharge and local field potential oscillations in primate motor cortex during voluntary movements.</a> J. Neurophysiol. 79, 159-173 (1998).</li><li>Abbott, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Laboratory+animals:+the+Renaissance+rat.">Laboratory animals: the Renaissance rat.</a> Nature. 428, 464-466 (2004).</li><li>Fuster, 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> The prefrontal cortex. , (2008).</li><li>Britten, K. H., Shadlen, M. N., Newsome, W. T., Movshon, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+analysis+of+visual+motion:+a+comparison+of+neuronal+and+psychophysical+performance.">The analysis of visual motion: a comparison of neuronal and psychophysical performance.</a> J. Neurosci. 12, 4745-4765 (1992).</li><li>Abbott, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroscience:+The+rat+pack.">Neuroscience: The rat pack.</a> Nature. 465, 282-283 (2010).</li><li>Uchida, N., Mainen, Z. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Speed+and+accuracy+of+olfactory+discrimination+in+the+rat.">Speed and accuracy of olfactory discrimination in the rat.</a> Nat. Neurosci. 6, 1224-1229 (2003).</li><li>Jaramillo, S., Zador, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+auditory+cortex+mediates+the+perceptual+effects+of+acoustic+temporal+expectation.">The auditory cortex mediates the perceptual effects of acoustic temporal expectation.</a> Nat. Neurosci. 14, 246-251 (2010).</li><li>Cohen, L., Rothschild, G., Mizrahi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multisensory+integration+of+natural+odors+and+sounds+in+the+auditory+cortex.">Multisensory integration of natural odors and sounds in the auditory cortex.</a> Neuron. 72, 357-369 (2011).</li><li>Desch&#234;nes, M., Moore, J., Kleinfeld, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sniffing+and+whisking+in+rodents.">Sniffing and whisking in rodents.</a> Curr. Opin. Neurobiol. 22, 243-250 (2012).</li><li>Raposo, D., Sheppard, J. P., Schrater, P. R., Churchland, A. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multisensory+decision-making+in+rats+and+humans.">Multisensory decision-making in rats and humans.</a> J. Neurosci. 32, 3726-3735 (2012).</li><li>Bari, A., Dalley, J. W., Robbins, T. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+application+of+the+5-choice+serial+reaction+time+task+for+the+assessment+of+visual+attentional+processes+and+impulse+control+in+rats.">The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats.</a> Nat. Protoc. 3, 759-767 (2008).</li><li>Brasted, P. J., Dunnett, S. B., Robbins, T. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Unilateral+lesions+of+the+medial+agranular+cortex+impair+responding+on+a+lateralised+reaction+time+task.">Unilateral lesions of the medial agranular cortex impair responding on a lateralised reaction time task.</a> Behav. Brain Res. 111, 139-151 (2000).</li><li>Gage, G. J., Stoetzner, C. R., Wiltschko, A. B., Berke, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+activation+of+striatal+fast-spiking+interneurons+during+choice+execution.">Selective activation of striatal fast-spiking interneurons during choice execution.</a> Neuron. 67, 466-479 (2010).</li><li>Erlich, J. C., Bialek, M., Brody, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+cortical+substrate+for+memory-guided+orienting+in+the+rat.">A cortical substrate for memory-guided orienting in the rat.</a> Neuron. 72, 330-343 (2011).</li><li>Mohebi, A., Oweiss, K. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+ensemble+correlates+of+working+memory+in+the+rat+medial+prefrontal+cortex.">Neural ensemble correlates of working memory in the rat medial prefrontal cortex.</a> 41 st Ann. Meet. Soc. Neurosci. , (2011).</li><li>Oweiss, K. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Statistical signal processing for neuroscience and neurotechnology. , (2010).</li><li>Thorndike, E. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+intelligence:+An+experimental+study+of+the+associative+processes+in+animals.">Animal intelligence: An experimental study of the associative processes in animals.</a> Psychol. Monographs: Gen. Appl. 2, 1-109 (1898).</li></ol>

Rats have been widely used in neuroscience research for over a century. Since Thorndike&#39;s introduction of the concept of the law of effect in cats34, operant conditioning has been the standard approach to test different aspects of animal behavior. Many neuroscience experiments involving decision making and motor preparation include a delay period between the instruction cues and the action interval. It is desirable to minimize movements during these delay periods to reduce any confounds to the neural data ...

Studying the relation between neurophysiology and behavior is the ultimate goal in systems neuroscience. Historically, there has been a tradeoff between animal model choice and behavioral repertoire1-5. While simple organisms like sea slugs6 or squids7 have been used extensively to study properties of single ion channels, neurons and simple neural circuits, higher order species are needed to study more complex functions such as spatial navigation, decision making8-11 and cognitive control12-14. Despite being a standard animal model for human like behavior, use of nonhuman primates prompts cost and ethical considerations that precludes their use across a wide range of experiments in a single laboratory setting15-18. Simpler animal models such as rodents are generally preferred19, provided they have similar neural substrates underlying the behaviors of interest.
There's ample evidence suggesting that rodents share similar cortical and subcortical structures as those found in primates20-22. Rodents are also known to integrate information across multiple sensory modalities to guide their action23-25, for example, by coordinating whisking and sniffing during exploratory behavior26 or by integrating auditory and visual/olfactory events25,27.
Here we describe a framework for operant conditioning of rodents used to test cognitive tasks28-32. In this framework, subjects are required to fixate inside a nosepoke hole and maintain their snout inside the hole until the presentation of a go cue. The behavioral task is a five-hole nosepoke design that is conventionally used for 5-choice serial reaction time task studies. During the delay period, a range of instruction cues is presented to guide the subject to perform an action. This framework can easily be modified to suit a wide range of experiments in which training the subject to minimize its overt movement over a brief interval is needed. This permits studying the extent to which spiking activity of individual neurons is affected by specific cues during this interval. The protocol can minimize the training time and can reduce across-subject learning variability. A schematic flowchart of the task is shown in Figure 1.

<table border="0" cellpadding="0" cellspacing="0" width="757">
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	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:359px;"> 5-HOLED NOSE POKE WITH 3STIM CUE LIGHT - RAT CAGE</td>
			<td style="width:112px;">Coulbourn</td>
			<td style="width:119px;"> H21-06M/R</td>
			<td style="width:167px;"> </td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:359px;">TEST CAGE</td>
			<td style="width:112px;">Coulbourn</td>
			<td style="width:119px;">H10-11R-TC</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:359px;">Graphic State Software</td>
			<td style="width:112px;">Coulbourn</td>
			<td style="width:119px;"> </td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:359px;">PROGRAMMABLE TONE/NOISE GENERATOR</td>
			<td style="width:112px;">Coulbourn</td>
			<td style="width:119px;">A12-33</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:359px;">Dustless Precision Pellets</td>
			<td style="width:112px;">Bio-Serv</td>
			<td style="width:119px;">F0165</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:359px;"> SPEAKER MODULE</td>
			<td style="width:112px;">Coulbourn</td>
			<td style="width:119px;">H12-01R</td>
			<td></td>
		</tr>
	</tbody>
</table>

a fully automated rodent conditioning protocol for sensorimotor integration and cognitive control experiments

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. Higher cognitive functions that require precise control over sensorimotor responses such as decision-making and attentional modulation, however, are typically assessed in nonhuman primates. Despite the richness of primate behavior that allows multiple variants of these functions to be studied, the rodent model remains an attractive, cost-effective alternative to primate models. Furthermore, the ability to fully automate operant conditioning in rodents adds unique advantages over the labor intensive training of nonhuman primates while studying a broad range of these complex functions.
Here, we introduce a protocol for operantly conditioning rats on performing working memory tasks. During critical epochs of the task, the protocol ensures that the animal's overt movement is minimized by requiring the animal to 'fixate' until a Go cue is delivered, akin to nonhuman primate experimental design. A simple two alternative forced choice task is implemented to demonstrate the performance. We discuss the application of this paradigm to other tasks.

The suggested framework enables training the subject on a range of cognitive tasks. Here we implemented an instructed delay task designed to investigate the mechanisms of goal-directed actions in the rodent prefrontal cortex. Figure 1 shows a flowchart of the experimental design.
To ensure that the subject understands the task requirement at every step, performance measures should be continuously assessed. Figure 2 shows an example performance of one subject a...

Watch this Scientific Journal Video about A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments at JoVE.com

A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments

A fully automated protocol for rodent operant conditioning is proposed. The protocol relies on precise temporal control of behavioral events to investigate the extent to which this control influences neural activity underlying sensorimotor integration and cognitive control experiments.

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. ...

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