Name: A Fully Automated and Highly Versatile System for Testing Multi-cognitive Functions and Recording Neuronal Activities in Rodents (Video) | JoVE Journal
Uploaded: 2012-05-03T12:00:00.000+00:00
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Description: Learn a fully automated system for testing multi-cognitive functions and recording neuronal activities in rodents. This versatile method enables simultaneous behavioral and electrophysiological studies.

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This work was supported by the Neurosciences Research Foundation and grants from The Blasker-Rose-Miah Fund of The San Diego Foundation and The G. Harold and Leila Y. Mathers Charitable Foundation.

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<li>Bieszczad, K. M., Weinberger, N. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Learning+strategy+trumps+motivational+level+in+determining+learning-induced+auditory+cortical+plasticity%5BTitle%5D)+AND+%22Neurobiology+of+Learning+and+Memory%22%5BJournal%5D)">Learning strategy trumps motivational level in determining learning-induced auditory cortical plasticity.</a> Neurobiology of Learning and Memory. 93, 229-239 (2010).</li>
<li>Sagvolden, T. I. mpulsiveness, overactivity, <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((poorer+sustained+attention+improve+by+chronic+treatment+with+low+doses+of+l-amphetamine+in+an+animal+model+of+Attention-Deficit%2FHyperactivity+Disorder+%28ADHD%29%5BTitle%5D)+AND+%22Behav.+Brain+Funct%22%5BJournal%5D)">poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).</a> Behav. Brain Funct. 7, 6(2011).</li>
<li>Sagvolden, T., Johansen, E. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Rat+Models+of+ADHD%5BTitle%5D)+AND+%22Curr.+Top+Behav.+Neurosci%22%5BJournal%5D)">Rat Models of ADHD.</a> Curr. Top Behav. Neurosci. , (2011).</li>
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<li>Johnson, K. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Sensory+discrimination%3A+neural+processes+preceding+discrimination+decision%5BTitle%5D)+AND+%22J.+Neurophysiol%22%5BJournal%5D)">Sensory discrimination: neural processes preceding discrimination decision.</a> J. Neurophysiol. 43, 1793-1815 (1980).</li>
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<li>Fraser, L. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Measuring+anxiety-+and+locomotion-related+behaviours+in+mice%3A+a+new+way+of+using+old+tests%5BTitle%5D)+AND+%22Psychopharmacology+%28Berl%29%22%5BJournal%5D)">Measuring anxiety- and locomotion-related behaviours in mice: a new way of using old tests.</a> Psychopharmacology (Berl). 211, 99-112 (2010).</li>
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<li>Feduccia, A. A., Duvauchelle, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Auditory+stimuli+enhance+MDMA-conditioned+reward+and+MDMA-induced+nucleus+accumbens+dopamine%2C+serotonin+and+locomotor+responses%5BTitle%5D)+AND+%22Brain+Res.+Bull%22%5BJournal%5D)">Auditory stimuli enhance MDMA-conditioned reward and MDMA-induced nucleus accumbens dopamine, serotonin and locomotor responses.</a> Brain Res. Bull. 77, 189-196 (2008).</li>
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Production and Free Access of this video-article is sponsored by Med Associates, Inc.

A critical aspect in design of any auditory behavioral task is elimination of unwanted sounds resulting from scattering and deflection in the test environment. Poor sound control can have a significant effect on the behavior being tested and will produce misleading or even uninterpretable results. The behavioral chamber used in the system described here is specifically designed to be acoustically transparent in order to avoid sound deflection from the chamber walls. Indeed, when measured from the center of the chamber, sound deflection was effectively undetectable (data not shown).
Although we developed this system mainly for studying the auditory system, it can be easily adapted by other researchers to study other sensory systems. Modifications can be made easily on both software and hardware for different tasks without changing the overall configuration of the system. The modular operation panel makes the system particularly versatile by allowing for addition and/or substitution of different devices for new behavioral tasks. For instance, olfactory behavioral tasks can be implanted by delivering olfactory stimulus into the nose poke device. The five choice illuminated nose poke wall with olfactory stimulus from the MED Associates (ENV-115A-OF) can be easily installed on the operation panel for complex olfactory tasks. In addition, all the operant devices can be easily replaced with those that are designed for mice without changing the configuration of the system.
Precise temporal control of each operant device, as well as high resolution recording of single events in a given trial, enable accurate manipulation of the devices for customizing the design of behavioral tasks to address different cognitive brain functions (see below). When combined with neuronal activity recording, a rich variety of issues in the field of neurosciences can be studied with this system. For instance, in the auditory task described above, the following questions related to brain cognitive functions can be investigated in a single trial:
(1). Motivation: Since each trial is initiated by animal's "self-motivated" nose-poke action (Figure 5A-a and Figure 3), motivation can thus be assessed quantitatively by measuring the total number of trials performed by an animal in a given session, or the number of consecutive trials performed6,7.
(2). Attention: The key for obtaining a reward in a trial is to correctly recognize the auditory cues. In about 25% of rats that could not be trained to perform the task, lack of attending to the auditory cues was the major factor. In contrast, in the rats who learned the task, a momentary pause of behaviors was apparent during auditory cue presentation (see Figure 5A-b and Figure 3). By using this system, it is thus possible to (i) screen rats for "attention deficits" and (ii) study neural mechanisms of attention when combined with neuronal recordings while the animal is attending to the auditory cues8-10.
(3). Decision: Upon recognition of the auditory cues, the animal has to decide which direction to turn to approach the correct lever within a limited time window (Figure 5A-c). It is thus also an effective paradigm for studying decision-making11,12.
(4). Patience: The timing of lever extension can be controlled such that the animal has to wait for the lever after arriving at the spot where the lever will extend (Figure 5A-d). By varying the length of waiting, the extent of an animal's patience can be tested and quantified13.
(5). Rewards: The final goal of the task is to obtain the reward (Figure 5A-e and Figure 3). Behavioral tasks using this system can thus be easily designed to study many aspects of reward-decision issues and the function of the value systems of the brain14-17.

a fully automated and highly versatile system for testing multi-cognitive functions and recording neuronal activities in rodents

A Fully Automated and Highly Versatile System for Testing Multi-cognitive Functions and Recording Neuronal Activities in Rodents

We have developed a fully automated system for operant behavior testing and neuronal activity recording by which multiple cognitive brain functions can be investigated in a single task sequence. The unique feature of this system is a custom-made, acoustically transparent chamber that eliminates many of the issues associated with auditory cue control in most commercially available chambers. The ease with which operant devices can be added or replaced makes this system quite versatile, allowing for the implementation of a variety of auditory, visual, and olfactory behavioral tasks. Automation of the system allows fine temporal (10 ms) control and precise time-stamping of each event in a predesigned behavioral sequence. When combined with a multi-channel electrophysiology recording system, multiple cognitive brain functions, such as motivation, attention, decision-making, patience, and rewards, can be examined sequentially or independently.

In this report, we present a fully automated and highly versatile system capable of simultaneously testing multi-cognitive behaviors and recording neuronal activities for rodents.

We have developed a fully automated system for operant behavior testing and neuronal activity recording by which multiple cognitive brain functions can be ...

The overall goal of this procedure is to train a rat to perform a sequence of tasks by which multiple brain functions can be investigated. This is accomplished by first acclimating the rats to the behavioral chamber. The second step is to train the rat to push a lever to obtain food pellets as rewards.Next, the rats are trained to reveal a hidden lever by poking their head into the nose poke hole. The final step is to train the rats to recognize a sensory cue and then to push the correct lever indicated by the queue. Ultimately, the rats learn the entire sequence of the tasks aimed at obtaining the rewards.We have developed a a fully automated system for right behavioral testing and neuronal activity recording. Using this system, multiple brain functions can be investigated. The unique future of this system is a customer made acoustically transparent chamber, which is ideal for auditory task training.Another feature of this system is that different operant devices can be added easily, which makes the system quite versatile, allowing the implementation of a variety of auditory, visual, and audiovisual behavioral tasks. The system is composed of three major components, a double walled soundproof room, a multiple channel electrophysiological recording system, and a fully automated behavioral testing system. A custom designed opera in chamber sits inside the soundproof room.The chamber consists of three acoustically transparent walls and one modular operation panel to monitor and record behavior. A video camera is mounted above the opera in chamber. An interface box transmits signals back and forth between the chamber and a computer.Auditory cues are generated by a calibrated programmable audio generator and are delivered via three speakers located on the operation panel for visual cues, a stimulus light and two triple stimulus displays are located on the middle and side panels. A nose poke device with three color LED lights is mounted at the bottom of the middle panel. An infrared detector installed within the nose poke unit records, nose poking and holding.Period two removable retractable response levers are mounted on each side of the operation. Panel rewards are provided by two pellet dispensers that drop food into the pellet receptacles. Four pairs of infrared beams are placed at the bottom of the chamber to both indicate the position of the animal and to control devices based on the animal's position.Lastly, cables from a head stage are connected to a commutator for recording neuronal activity. The experimental protocol is fully automated via programs created within the Med PC four software platform. Behavioral data are saved and translated to Microsoft Excel files then imported into and analyzed with matlab.Before training, limit the food intake until the animal's weight is 90%of baseline. To prepare the chamber for acclimation, retract the levers, block the nose poke hole with a rubber stopper, and place about 20 pellets of food into each pellet. Receptacle now place a naive animal into the chamber for acclimation.The rat will soon start to explore the food cups and eat the pellets. When both food cups are empty, use the software to dispense a single pellet into each tray. In doing so, the rat will learn to associate food with the cup.Force the rat to move to both sides of the chamber by dispensing pellets randomly into each food cup. One session is usually enough for establishing the Food Cup Association In a new session, extend both levers into the chamber and leave the food cup empty. Next place an acclimated rat into the chamber.When the animal enters the vicinity of a lever, dispense a pellet. Also provide rewards when the rat shows interest in the lever, such as sniffing, touching, or climbing. An accidental lever push should also trigger a reward.To encourage lever pushing and to force exploration of both levers, allow the animal to push each lever consecutively a limited number of times when the limit is reached, retract the lever. Extend both levers to repeat the procedure. Gradually decrease the limit until the lever retracts every time it is pushed.One to two sessions are usually enough for establishing the lever. Push Food reward Association. In a new session, retract the levers.Remove the rubber stopper from the nose poke hole, and place several food pellets in the nose. Poke device. Reintroduce the animal into the chamber and extend one of the two levers randomly.When the rat sniffs the nose poke hole for food pellets, seeing the extended lever, the rat will approach and push the lever to obtain a food pellet. After the is pressed and the reward is dispensed, retract the lever to encourage the rat to explore the nose poke device. It usually takes one 30 minute session for a rat to learn the task sequence, nose, poke, lever, push rewards.In another new session, place the animal into the chamber to begin Q training. After the animal performs a nose poke event, play a distinct auditory cue. Extend both right and left levers.After each auditory cue presentation, reward the rat only when it pushes the lever that is indicated by the auditory cue, the animal will gradually learn to associate a specific auditory cue. With one lever. The animal should now be able to perform the intended full sequence of training, nose, poke, cue, lever, push, reward, or no reward.Allow the rat to practice the newly learned task until a consistent performance level is reached. The session is limited to 30 minutes. This system can be used to perform the two alternative choice pitch discrimination task, which examines the frequency discrimination threshold of a rat.After training the rats to quickly push the correct lever indicated by an auditory cue, an auditory learning curve is obtained. Each colored line represents the discrimination frequency variations of an individual animal. The dark line represents the averaged learning curve.On average, it took about seven sessions of training to attain the 75%hit rate.Criterion. Animal behavior in this task can also be quantitatively characterized by several measurements, including the reaction time relative to the onset of the auditory queue, the inter trial interval, and the temporal dynamics of performance. Multiple cognitive brain functions can also be investigated using this system.The top captions describe each action in sequence of one trial. The bottom captions indicate the cognitive behavioral functions that can be studied when combined with electrophysiology. Recording the neural basis of the cognitive behavioral functions can also be studied.This plot shows a neuron recorded in the nucleus space ssus of a rat performing the two alternative choice pitch discrimination task. While this plot shows a neuron recorded in the ventral segmental area, When attempting this procedure is important to pay close attention to, to differences between rats and their behavioral characteristics, and cognitive ability, training procedures and parameters should be individualized for best training results. Although we developed this system mainly for study auditor system, it can be easily adapted by other research to study a visual system and multiple cognitive brain functions such as motivation, attention, patients, and rewards.

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JoVE Journal

Neuroscience

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Learn a fully automated system for testing multi-cognitive functions and recording neuronal activities in rodents. This versatile method enables simultaneous behavioral and electrophysiological studies.

A Fully Automated and Highly Versatile System for Testing Multi-cognitive Functions and Recording Neuronal Activities in Rodents (Video) | JoVE Journal

A Fully Automated and Highly Versatile System for Testing Multi-cognitive Functions and Recording Neuronal Activities in Rodents

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