Name: the rodent psychomotor vigilance test (rpvt): a method for assessing neurobehavioral performance in rats and mice
Uploaded: 2016-12-29T12:00:00.000+00:00
Duration: 7 min 47 s
Description: Watch this Scientific Journal Video about The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice at JoVE.com

This research was supported by NASA (NNX15AC17G to CMD), and by NASA cooperative agreement NCC 9-58 (E000010 to CMD, NBPF02802 and NBPF04201 to RDH) with the National Space Biomedical Research Institute.

Laboratory animal care was according to Public Health Service (PHS) Policy on the Humane Care and Use of Laboratory Animals. All procedures were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The Institutional Animal Care and Use Committee of the Johns Hopkins University approved the protocol and all procedures. Johns Hopkins also maintains accreditation of their program by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC).
1. Animals
<ol>
	<li>Use adult male Long Evans rats (approximately 10 - 12 weeks old at the start of behavioral training), although other strains are suitable, including inbred rats.</li>
	<li>Upon arrival in the colony, house rats singly in approved caging and rooms, due to the food restriction needs described below. Acclimate animals to the housing situation as well as handling for several days prior to starting the food restriction procedure (approximately 7 days).</li>
	<li>Provide rat chow ad libitum for 1 - 2 weeks to allow rats to achieve a &#34;free-feeding&#34; weight. Once at this weight, restrict food access to reduce rats&#39; weights, over 1 - 2 weeks, to 85 - 90% of the free-feeding weight. Maintain animals at 85 - 90% of their free-feeding weights during behavioral training and testing. Start with 15 - 18 g of food per day and adjust this amount based on whether or not a rate is maintaining its target weight. 
	NOTE: Food restriction normally requires approval of one&#39;s institutional ACUC or other regulatory body prior to starting the restriction.</li>
	<li>Weigh animals daily and record the weight on weight sheets. Ensure weighing is done at the same time and on the same scale each day prior to the start of any behavioral training or feeding. 
	NOTE: Only start pretraining (below) when the animals have achieved their target weights. This practice allows for immediate corrections to food amounts for animals that are either under or over their target weights. It also provides a method to determine if rats are maintaining weights at 24-h intervals. Also avoid weighing rats at different times of the day; it will result in dramatic differences in weight, incorrect feedings, and poor behavioral performances.</li>
	<li>Provide fresh water at all times in the home cage by the use of glass or plastic bottles with rubber stopper tops and sipper tubes.</li>
	<li>When sessions are not conducted (e.g., weekends, holidays), feed the rats their normal allotment of rat chow to maintain weight stability. Weigh rats to determine if more food is needed to maintain weight during these times.</li>
</ol>
2. Equipment and Software
<ol>
	<li>Use standard modular operant chambers equipped with one nose poke key, a house light, and a pellet dispenser (i.e., feeder).</li>
	<li>Place the modular nose poke key on either side of the centrally located pellet dispenser; ensuring that this placement remains consistent in other operant chambers and across studies. Here, the nose poke key is on the left hand side of the pellet dispenser.</li>
	<li>Place the modular house light high on the back wall of the chamber so as to not interfere with other behaviors.</li>
	<li>Use rat food pellets (e.g., Noyes 45-mg pellets or similar) for reinforcement. The feeder model determines food pellet size, but most rat feeders use 45-mg food pellets (mouse feeders typically use 20-mg food pellets). Use standard chow pellets, but other pellets can be purchased (e.g., sucrose) for different experimental manipulations.</li>
	<li>Control stimulus presentations, nose poke response inputs, reinforcement delivery, and data collection via an interface connected to a computer. Contact the authors for specific information regarding behavioral programs written with a programming language specifically designed for behavioral testing (see Table of Materials and Reagents). 
	NOTE: It is important to record independent and dependent variables on a trial-by-trial basis, including animals&#39; response types (e.g., correct responses, premature responses, misses), the response latency, and number of trials presented. When using different strains, sexes or species, these variables can be easily altered to maximize training in almost any type of rodent.</li>
</ol>
3. Pretraining
<ol>
	<li>Assign each animal to an operant chamber where it will be tested each day, and at approximately the same time of day, throughout the experiment.</li>
	<li>Weigh the rat and place it in its specific operant chamber with food pellets in the pellet dispenser. Place 10 - 20 food pellets in the receptacle for the rat to eat.</li>
	<li>For pretraining, set the following parameters to low, fixed values: foreperiod value = 2 s, timeout value = 2 s, limited hold = 10 s.</li>
	<li>Start the computer program to control presentation of the house light, nosepoke key illumination, and automatic food pellet delivery. 
	NOTE: It is best to have the behavioral program set to a level that allows for frequent reinforcements for the majority of responses produced by the animal, such that the nose poke key is illuminated for a relatively long duration of time (e.g., 10 s). This increases the likelihood that the rat will poke the key while it is illuminated, resulting in the delivery of a food reinforcer by the computer program.</li>
	<li>Once the rat finishes the food pellets, start the shaping process by reinforcing the rat when it approaches the food receptacle or the nose poke key. Here, manually shape each rat, which means that an experimenter watches the rat&#39;s behavior (by leaving the sound attenuating cubicle doors open) and delivers pellets from the feeder as quickly as possible after the rat emits the desired behavior. Deliver pellets from a button on the feeder itself, through a hand-held switch that is wired to the feeder, or through the computer software used to control the behavioral contingencies by clicking on the appropriate output on the interface.</li>
	<li>Using the method of shaping by successive approximations, provide a food reinforcer for behavior changes that are successive approximations to the final desired behavior23. For example, once the rat is reliably retrieving food pellets from the food receptacle, start reinforcing only movement towards or around the nose poke key, and no longer reinforce approaches to the food receptacle. Here, shape rats to move to the left after retrieving a food pellet, since the nose poke key is located to the left of the food receptacle in the operant chambers. 
	NOTE: Even though the experimenter is delivering food reinforcers during the beginning of pretraining, the computer program is still running and controlling the house light, nosepoke key, and feeder. If a rat pokes the key, the computer program will reinforce it automatically. Experimenter-reinforced behaviors are only those leading the rat to poke the illuminated key, such as sniffing the key or around it, moving the head near the key or towards it, etc.</li>
	<li>Determine the amount of food earned during the pretraining session by counting the number of pellets delivered manually plus any pellets delivered automatically by the computer software (i.e., pellets delivered because the rat poked the illuminated key). Multiply this number by 0.045 g to determine total food earned (e.g., 30 pellets x 0.045 g = 1.35 g).</li>
	<li>Remove the rat and place it back in its home cage. Subtract, by hand, the amount of food earned (see 3.7) in the behavioral session from the rat&#39;s daily food allotment. Feed the remainder of the food allotment to the rat after the behavioral training session. Feed at a minimum of 30 min after the conclusion of the behavioral session to avoid home cage food reinforcement immediately after nonproductive sessions.</li>
	<li>Clean the operant chamber daily with a gentle disinfectant (e.g., soap and water). Use 70% EtOH sparingly, given that it can damage the operant chambers. Check the nose poke key daily in order to maintain proper working condition and clean with disinfectant when needed, since a key that sticks or gets locked in place will disrupt an animal&#39;s performance if not repaired quickly.</li>
	<li>Shape each rat in this manner until the rat emits 40 - 50 correct computer-reinforced (not manually or experimenter-reinforced) responses on the illuminated key, retrieves each food pellet, and returns to and pokes the nose poke key without additional shaping. Typically, rats require approximately 2 - 3 30-min sessions to reach these criteria (see Figure 2). 
	NOTE: Manual delivery of food pellets is not needed after the rat is reliably poking the key and receiving food reinforcement delivered by the computer program.</li>
</ol>
4. rPVT Training
<ol>
	<li>Once shaped, start the rat at a fixed, relatively short foreperiod interval and TO value (e.g., 2 s) on the next 30-min session until the rat completes 8 out of 10 correct trials. For each of these trials during the training, illuminate the nose poke key for a period of time long enough for a rat to make a response. Here, keep the key illuminated for 9 seconds; this response window is also called the limited hold (LH).</li>
	<li>Use a relatively short time out (TO; e.g., 2 s) as a punishment for premature responses, or responding prior to the illumination of the nose poke key. During the TO, rats have no opportunity to earn food. Here, the TO and foreperiod value are the same duration during these training sessions and change at the same rate.</li>
	<li>Once the rat completes 8 out of 10 correct trials, increase the foreperiod and TO by 0.1 s (i.e., to 2.1), while shortening the LH by 0.1 s (i.e., to 8.9). It is best to use a computer program that can automatically make these adjustments during a session. 
	NOTE: When training mice on the rPVT, a longer ITI is employed since mice require more time to consume food pellets. Here, use a 30 s ITI for training and testing male C57BL/6J. Additionally, since a mouse may weigh ~ 20 g, it will consume significantly fewer pellets during a session. Therefore, shorten a typical session by having it end when a maximum of 50 pellets are earned; the criterion for increasing the foreperiod and TO is also changed to be 4 out of 5 correct trials before increasing the foreperiod and TO by 0.1 s.</li>
	<li>Once the 30 min session is over, record the final foreperiod the rat reached during the training session (e.g., 4.2 s), either in a spreadsheet or by hand on a data sheet, and the amount of food earned, which is calculated by multiplying the number of correct trials times 0.045 g (e.g., 100 correct trials x 0.045 g = 4.5 g). Subtract this food amount from the rat&#39;s daily allotment and feed the rat the remaining food in the home cage. 
	NOTE: The daily data files record the final foreperiod reached by each rat. The calculation to determine the amount of food earned in the session can be done automatically by the computer program or by hand using the equation above. Food earned is subtracted by hand from each rat&#39;s the daily food allotment.</li>
	<li>On the following day, start the 30 min training session with a foreperiod that is 300 ms lower than the value the rat ended on in the previous session. For example, if the rat ended at 4.2 s, this session starts at 3.9 s. Continue increasing the foreperiod by 0.1 s as the rat completes 8 out of 10 correct trials at each foreperiod, until rats reach a foreperiod of 10 s. In this way, rats will experience all of the possible foreperiods. 
	NOTE: When rats reach a foreperiod of 9.7 - 10 s, the TO remains at 8 s and the LH is 1.5 s.</li>
	<li>At the end of each session, check the rat&#39;s daily performance during this time by examining the percentage of correct trials, premature trials, and misses. Rats commonly maintain an average of 40 - 90% correct responses during these training sessions, with the average percent correct increasing steadily across training. Here, export the daily data for each rat to a spreadsheet that calculates these percentages in order to track daily session performance.</li>
	<li>Once the rat reaches a foreperiod of 10 s, start the next subsequent 30 min session with the foreperiods presented at random intervals, starting with foreperiods between 7 - 10 s. Ensure that the TO and LH remain at 8 and 1.5 s, respectively. Here, the computer program controlling the behavioral contingencies automatically switches from presenting ascending foreperiods to variable foreperiods once each rat reaches the 8 out of 10 criterion at the 10 s foreperiod.</li>
	<li>Once the rat maintains at least 70% correct with randomly presented foreperiods between 7 - 10 sec, change the program to present foreperiods at random intervals, starting with foreperiods between 5 - 10 s. Examine each rat&#39;s daily performance during this time because this change often happens within a session.</li>
	<li>After the rat maintains 70% correct, change the program again to present the full range of foreperiods (3 - 10 s) at random intervals during the 30 min session. In a manner similar to 4.8, examine each rat&#39;s daily performance during this time because this change often happens within a session. 
	NOTE: The computer software controlling the behavioral contingencies automatically makes these changes based on each rat&#39;s performance (e.g., 4.7 - 4.9). It is important to only make the change in 4.9 when a rat&#39;s success rate is high (&#62;70% correct), since rats frequently adopt the strategy of responding randomly in time, instead of properly waiting and attending to the stimulus. If a rat&#39;s success rat is low, repeat 4.7 - 4.9.</li>
	<li>For the Acquisition Criteria, define the baseline performances as stable when, on 4 out of 5 daily sessions within a week, rats&#39; percentage of correct responses is 75% or greater during a session and the percentage of premature responses is less than 30%.</li>
</ol>
5. Data Analysis for Basic Response Measures
<ol>
	<li>To assess behavioral performances during acquisition, use repeated-measures ANOVAs, with the repeated factor of either Session, Time on Task Value, or Foreperiod Value for each performance measure described below. 
	NOTE: Here, the studies use both within- and between-subjects designs, where we compare all animals to their own baselines after an experimental condition and compare experimental animals to control animals following the same manipulation. When stable behavioral baselines are achieved, use of within-subjects designs will limit the number of rats needed.</li>
	<li>Define premature responses as responses prior to the onset of the key light or within the first 150 ms of the key light being on.</li>
	<li>Define correct responses as responses made after the key light comes on, with a minimal latency greater than 150 ms, and a maximal latency of the response window length; here, 1,500 ms.</li>
	<li>Define misses (or omissions) as trials on which the subject fails to make a response.</li>
	<li>Define response latencies as the elapsed time (in ms) from light onset to depression of the nose poke key; also called reaction time (RT).</li>
	<li>Define total trials as the number of premature responses plus correct responses plus misses. 
	NOTE: In human PVT performances, premature responding and lapses in attention can be quite rare, and investigators most often report only the actual raw frequencies of these measures. However, this is not the case in performances with rats. To allow for comparisons between different versions of the rPVT in the literature, rats&#39; performance measures are presented here as a percentage of total trials. Use of a computer program that can record and label each of these items on a trial-by-trial basis for subsequent analysis is preferred, since rats will complete over 200 trials per 30 min session and will often meet the criteria to move to another step in the training procedure within a session.</li>
</ol>
6. Additional Computed Performance Measures
<ol>
	<li>For a 30 min behavioral session, define lapses as correct responses in which the RT was greater than twice the mean reaction time for each rat&#39;s session (done after a session); also include missed trials in the lapse calculation. 
	NOTE: In the human PVT, lapses are typically defined as reaction times (RT) &#62; 500 ms4. For rodents, it is best to perform post-hoc comparisons to each rat&#39;s mean RT - acquired from the trial-by-trial analysis described above - instead of comparing them to a threshold value, due to the variability in RTs from individual rats. This method is similar to lapses in other published versions of the rPVT15,16. Here and in other published versions, lapses also include missed trials (lapses = responses with RTs &#62; twice the mean RT for a session, plus misses) because missed trials in the human PVT are recorded as lapses, as well.</li>
	<li>Determine the estimated false alarm rate by calculating the percentage of premature responses that occur during the actual 3 - 10 s interval when a stimulus could have appeared. 
	NOTE: This measure uses a subset of premature responses that occur only during a time when the stimulus could occur, i.e., premature responses that occur within the 3 - 10 s foreperiod window. This measure does not include premature responses prior to the 3 s because the stimulus light would never be illuminated during that time. Here, this subset of premature responses is automatically sorted from all premature responses in a spreadsheet computer program.</li>
</ol>

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D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deficits+in+Sustained+Attention+and+Changes+in+Dopaminergic+Protein+Levels+following+Exposure+to+Proton+Radiation+Are+Related+to+Basal+Dopaminergic+Function.">Deficits in Sustained Attention and Changes in Dopaminergic Protein Levels following Exposure to Proton Radiation Are Related to Basal Dopaminergic Function.</a> PLoS One. 10, 0144556 (2015).</li><li>Stebbins, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Response+latency+as+a+function+of+amount+of+reinforcement.">Response latency as a function of amount of reinforcement.</a> J Exp Anal Behav. 5, 305-307 (1962).</li><li>Stebbins, W. C., Lanson, R. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Response+latency+as+a+function+of+reinforcement+schedule.">Response latency as a function of reinforcement schedule.</a> J Exp Anal Behav. 5, 299-304 (1962).</li><li>Christie, M. A., McCarley, R. W., Strecker, 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=Twenty-four+hours,+or+five+days,+of+continuous+sleep+deprivation+or+experimental+sleep+fragmentation+do+not+alter+thirst+or+motivation+for+water+reward+in+rats.">Twenty-four hours, or five days, of continuous sleep deprivation or experimental sleep fragmentation do not alter thirst or motivation for water reward in rats.</a> Behav Brain Res. 214, 180-186 (2010).</li><li>Koban, M., Sita, L. V., Le, W. W., Hoffman, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep+deprivation+of+rats:+the+hyperphagic+response+is+real.">Sleep deprivation of rats: the hyperphagic response is real.</a> Sleep. 31, 927-933 (2008).</li><li>Moody, D. B., Stebbins, W. C. <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 Psychophysics, The Design and Conduct of Sensory Experiments. , 277-302 (1970).</li><li>Pfingst, B. E., Hienz, R. D., Kimm, J., Miller, 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=Reaction-time+procedure+for+measurement+of+hearing+I.+Suprathreshold+functions.">Reaction-time procedure for measurement of hearing I. Suprathreshold functions.</a> J Acoust Soc Am. 57, 421-430 (1975).</li><li>Stebbins, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auditory+reaction+time+and+the+derivation+of+equal+loudness+contours+for+the+monkey.">Auditory reaction time and the derivation of equal loudness contours for the monkey.</a> J Exp Anal Behav. 9, 135-142 (1966).</li><li>Hienz, R. D., Weerts, E. M., VandeBerg, J. L., Williams-Blanger, S., Tardif, S. 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> The Baboon in Biomedical Research. , (2009).</li><li>May, B. J., Huang, A. Y., Aleszczyk, C. M., Hienz, R. D., Klump, G. M., Dooling, R. J., Fay, 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=.">.</a> Methods of Comparative Acoustics. , 95-108 (1995).</li></ol>

The authors have nothing to disclose.

The methodology described herein results in rPVT performances in rats that compare favorably in many aspects to the typical PVT performance reported in the human literature. Using the present techniques, one can quickly train rats to perform the rPVT, and the performances obtained with these techniques are characterized by clear discriminations (i.e., high levels of correct responding, low levels of both premature responding and lapses). Further, the reaction time distributions obtained with the rPVT are quite s...

The human psychomotor vigilance test (PVT) is a widely used, well-validated tool for measuring vigilance and sustained attention in humans, and was originally developed by Dinges et al. 1-3 for assessing the stability in reaction times and attention (e.g., errors in terms of premature responses and lapses in attention), both within sessions as a whole and across time within individual sessions. Over the years, the human PVT has been modified and updated4-11 to track temporal changes in various aspects attention, and has been demonstrated to be sensitive to changes in sleep deprivation and fatigue, and is affected by drug use and age of subjects12,13. The PVT is a seemingly simple procedure in which a subject briefly touches a screen when a stimulus (typically an LED number display) appears randomly in time, typically after 2 - 10 s. In the human version, the number display is incremented in ms and stopped when the screen is touched, thus indicating the subject&#39;s reaction time (RT). Decreases in vigilance are indicated by 1) slowed reaction times, 2) an increase in lapses (termed &#34;errors of omission&#34; in the human literature, and usually defined as RTs that are &#62; 500 ms in length), and 3) an increase in premature responding (termed &#34;errors of commission&#34; or &#34;false starts&#34; in the human literature). Other measures can also be obtained with the PVT for examining such variables as gender and age differences; for a review of these measures, see Basner and Dinges4. Finally, the PVT has been employed in the general area of human risk assessment, and has been successfully used under a wide range of operational areas that include the military, aviation and railway industries, first responders, and extreme environments such as NASA&#39;s Extreme Environment Missions Operations (NEEMO), the international Mars500 Project14, and on the International Space Station (ISS). On the ISS, the PVT is called the &#34;Reaction Self-Test&#34; and is employed to provide astronauts with individualized fatigue-related feedback (e.g., changes in RTs or lapses in attention).
The human PVT has been in use for decades, as have rodent versions of simple reaction time tasks (which are somewhat similar). It has been only recently, however, that a direct rodent counterpart to the human PVT has been reported in the literature. Christie and colleagues described a version of the human PVT for rats, and reported decreases in vigilance following sleep deprivation15,16. Additional recent studies have reported versions of the rPVT17-19. These reports have described changes in sustained attention following various sleep deprivation techniques; however, the data from these studies have also reported high levels of premature responding (e.g., in some cases, more than 40% of the total number of responses); such performances are quite unlike any PVT performances with humans. Such a large difference in rodent vs. human performances are likely due to differences in specific parameters employed in the human vs. the rodent versions of the PVT; for example, the Christie et al. study employed a randomly varying 3 - 7 s foreperiod, while a human PVT normally employs a 2 - 10 s foreperiod (although see Basner et al.5 for a 3-min version of the human PVT that uses a 1 - 4 s foreperiod). The use of relatively short foreperiod values can often result in animals &#34;timing&#34; their responses, and thus can promote, via accidental reinforcement, increased numbers of premature responses, as have been reported in the current rodent rPVT studies.
The version of the rPVT described here is based on our previously published article20, and provides a detailed description of the techniques and procedures involved. It differs from previously published versions of the rPVT in the following respects: 1) rats were trained with variable foreperiod values of 3 - 10 s, and 2) rats had to respond quickly, since only responses within a short response window (also termed a &#34;limited hold&#34;) following stimulus onset were reinforced (1.5 s in the present study; 3.0 s in the previous published versions of the rPVT). Using these modifications as well as brief timeouts for incorrect responding resulted in greater levels of stimulus control, as indicated by significant improvements in accuracy and reduced levels of premature responding. The present report also describes predictable changes in performance variables (e.g., lapses in attention, RTs) that parallel those seen in humans when examining vigilance decrements21, and when examining other performance measures including the human &#34;time on task&#34; effect and the response-stimulus interval (RSI) effect that is observed in the human PVT22.
The final version of the rPVT described here begins by turning on a house light (see Figure 1). After a variable interval (foreperiod) of 3 - 10 s elapses, the nose-poke key is illuminated for a maximum of 1.5 s. (To insure an equal distribution of foreperiods durations, values are randomly generated without replacement from a list of 36 possible values that range from 3 to 10 s, based on 200 ms increments.) Illumination of the nosepoke key is the signal for an animal to respond, and a response that occurs between 150 to 1,500 ms following the light onset is reinforced with a 45-mg pellet. After a reinforced response, both the nose-poke key light and the house light are turned off and a 1 s inter-trial interval (ITI; house light off) ensues. Nose-pokes at before light onset produce an 8 s timeout (TO) from the experimental contingencies that is signaled by extinguishing the house light. If no responses occur within the 1.5 s response window, both the nosepoke light and house light are turned off, and a 1 s ITI ensues. The next scheduled foreperiod value for the subsequent trial begins after either the 1 s ITI or the 8 s TO, whichever occurred during the prior trial. Sessions are conducted daily (5 days/week), normally consist of about 200 trials, and end after 30 min. This results with each trial having a duration of about 7.5 s, on average.
Shaping stable baseline performance on the rPVT is accomplished by 1) initially adapting a rat to take food pellets out of the food tray in the chamber, 2) hand-shaping a rat to respond on a nose poke key by reinforcing successive approximations to the final nose poke response, and 3) conducting daily sessions where the parameters of the rPVT procedure (i.e., foreperiod, ITI, TO, and key-illumination times) are gradually adjusted over a session, depending on how well each rat is performing during each session (described in detail below).

<table><tbody><tr><td>Modular rat operant chamber with stainless steel grid floor</td><td>Med Associates</td><td>ENV-008</td><td>Med Associates Inc.&lt;br/&gt; PO Box 319&lt;br/&gt; St. Albans, Vermont 05478,&lt;br/&gt; USA&lt;br/&gt; Phone: (802) 527-2343</td></tr><tr><td>Sound attenuating chamber&amp;nbsp;</td><td>Med Associates</td><td>ENV-022MD</td><td>Houses rat operant chamber</td></tr><tr><td>Houselight for rat</td><td>Med Associates</td><td>ENV-215M</td><td></td></tr><tr><td>1&quot; diameter rat nose poke response key</td><td>Med Associates</td><td>ENV-119M-1</td><td></td></tr><tr><td>Pellet receptacle, trough type</td><td>Med Associates</td><td>ENV-200R2M</td><td></td></tr><tr><td>Modular pellet dispenser for rat, 45-mg</td><td>Med Associates</td><td>ENV-203M-45</td><td></td></tr><tr><td>PCI Operating package for up to 8 operant chambers</td><td>Med Associates</td><td>MED-SYST-8</td><td></td></tr><tr><td>SmartCtrl</td><td>Med Associates</td><td>DIG-716P1</td><td>This catalog number has 8 outputs and 4 inputs which is the minimum needed to run the rPVT; SmartCtrl can also be purchased with 16 outputs and 8 inputs for more flexibility</td></tr><tr><td>Med-PC IV software</td><td>Med Associates</td><td>SOF-735</td><td></td></tr><tr><td>PC computer with PCI card slot</td><td>Any manfacturer (&lt;em&gt;e.g.&lt;/em&gt;, Dell)</td><td></td><td>Use of the PCI operating package requires a computer with a PCI card slot. Systems that use PCIe are available. Contact Med Associates for details.</td></tr><tr><td>Dustless Precision pellets 45-mg rodent grain-based diet</td><td>Bio Serv</td><td>FO165</td><td>Bio-Serv&lt;br/&gt; One 8th Street, Suite 1&lt;br/&gt; Frenchtown, NJ 08825, USA&lt;br/&gt; Phone: (800)-996-9908;&amp;nbsp;&amp;nbsp; Standard chow pellets are commonly used. Different pellets (&lt;em&gt;e.g.&lt;/em&gt;, sucrose) can be acquired from Bio Serv.</td></tr></tbody></table>

the rodent psychomotor vigilance test (rpvt): a method for assessing neurobehavioral performance in rats and mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

Baseline Rat rPVT Performances
With the parameters detailed here, 86.7% of the 122 male rats reached the final rPVT parameters within an average of 9.0 (SD = 10.13; n = 122) computer-automated training sessions (described in 4.1 - 4.9 rPVT Training; in our experience, only approximately 2% of rats will not acquire the rPVT). Using the current methodology, rats averaged 73.4% correct responding, 18.6% lapses in attention, and 10.6% ...

Watch this Scientific Journal Video about The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice at JoVE.com

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

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12.0K Views.  The Johns Hopkins University School of Medicine. A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

Video: The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

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.

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 ...

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.

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. ...

Behavioral Assessment of the Aging Mouse Vestibular System

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.

Motor control and balance performance are known to deteriorate with age. This paper presents a number of standard noninvasive behavioral tests with the addition of a simple rotary stimulus to challenge the vestibular system and show changes in balance performance in a murine model of aging.

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of ...

The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain&#160;to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.

The goal of this protocol is to perform a behavioral assay such as the attentional set shifting task (AST) to assess prefrontal cortex-mediated cognitive flexibility in mice.

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

Neurodevelopmental Reflex Testing in Neonatal Rat Pups

Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are also referred to as primitive reflexes. They are sensitive and consistent with later outcomes. Abnormal reflexes are described as an absence, persistence, reappearance, or latency of reflexes, which are predictive indices of infants that are at high risk for neurodevelopmental disorders. Animal models of neurodevelopmental disabilities, such as cerebral palsy, often display aberrant developmental reflexes, as would be observed in human infants. The techniques described assess a variety of neurodevelopmental reflexes in neonatal rats. Neurodevelopmental reflex testing offers the investigator a testing method that is not otherwise available in such young animals. The methodology presented here aims to assist investigators in examining developmental milestones in neonatal rats as a method of detecting early-onset brain injury and/or determining the effectiveness of therapeutic interventions. The methodology presented here aims to provide a general guideline for investigators.

Behavioral testing is the gold standard for determining outcomes following brain injury, and can identify the presence of developmental disabilities in infants and children. Neurodevelopmental reflexes are an early indicator of these abnormalities. A host of easily accomplished developmental reflex tests in the neonatal rodent were developed and described here.

Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are ...

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the animal&#39;s wellbeing and health. There are numerous behavioral tests that may be applied. We selected a test for general locomotion, the open field test (OFT); a test for muscular strength, the mesh test (MT); and a test for coordination, the rotarod test (RR). Testing can be accomplished on a weekly or monthly basis. As a test for general locomotion, the OFT works by objectively monitoring movement parameters while the mouse is in an open field apparatus. The field is generally a 2&#39; x 2&#39; box, and the movements are recorded through laser sensing or through video capture. The mouse is placed in the center of the open field and allowed to move freely for the test. The MT uses the latency for a mouse to fall off an inverted screen as a measure of muscular strength. A mouse is placed on a screen, which is inverted over a clear box, and is timed for their latency to fall. Three trials are performed, with the best of the three trials scored for that day. A score of 60 s is the maximum time a mouse is left inverted. Mice are given a 5-min rest period between mesh test trials. Lastly, an accelerated protocol on the RR assesses motor coordination and endurance. During a trial, a mouse walks on a rotating rod as it increases in speed from 4 rpm to 40 rpm over 5 min. The trial ends when the mouse touches the magnetized pressure sensor upon falling. Each mouse undergoes three trials, and the best trial is scored for that day. This combined behavioral data allows for the global assessment of mobility, coordination, strength, and movement of the test animals. At least two out of the three behavioral testing measures must show improvement for an animal to qualify as having overall improved motor function.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects of a disease or treatment on an animal's wellbeing. In order to globally assess motor functioning, we selected tests for general locomotion, muscular strength, and coordination: the open field test, the mesh test, and the rotarod test, respectively.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the ...

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to some Parkinson&#8217;s-like symptoms by destroying dopaminergic neurons in the substantia nigra of the brain. It has been thus used to establish PD models in various animal studies. Here, mice receive MPTP injections (20 mg/kg/day) for seven days and the behavioral tests are performed on the eighth day. This model is adapted efficiently in the study of PD. The behavioral tests here include the cylinder test and the open field test. The cylinder experiment is used to detect the animals&#8217; ability to lift their front paws when put into a different environment. As the PD model mice show arching&#8212;the mouse arches its back&#8212;the number of paw liftings decrease. This test is easy to execute. The open field test is used to detect the amount of time the mice spend on running, walking, and remaining immobile. We analyze animals&#8217; movements in open field using software and obtain data. Lastly, we use L-DOPA, one of the most commonly used PD drugs, as one example to show how to apply this model to the study of PD drugs. Our results indicate that MPTP neurotoxicity induces motor deficit which can be mitigated by L-DOPA.

We describe establishment of a murine model for Parkinson's disease using MPTP, and behavioral assessments using cylinder and open field tests to measure motor function. We then use L-DOPA as one example to show how to apply this model in the study of PD drugs.

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and ...

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

A comprehensive behavioral test battery of motor skills, mood&#8212;including social interaction, depression, and anxiety&#8212;and cognition is designed for the repeated assessment of neurodegeneration-related behavioral changes in mice.