Behavior
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Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage
Chapters
Summary August 4th, 2018
This paper describes a protocol for cognitive assessments for genetic models of the Alzheimer's disease using the IntelliCage system, which is a high throughput automated behavioral monitoring system with operant conditioning.
Transcript
This method can help answer key questions in the neuroscience field, such as animal models of cognitive deficits, or psychiatric diseases. The main advantage of this technique is that highly reproducible data of variety of cognitive tasks can be obtained with reduced manpower. Generally, individuals new to this method will struggle because the system needs many steps for the accurate work.
The designer software is where the experimental file which contains key experimental definitions, is produced. The experimental files are used for running specific tests, such as price preference, where only one of the four corners is not accessible within a specific time window. Begin by creating the animal list.
Define the conditions and set the parameters for the number of subject mice, number of genetic lines, sex of the animals, and number of the cage to be used. Then, select the appropriate transponder type, DataMars or Trovan in the central toolbar. Next, in the Groups panel, add or remove the experimental groups by pressing the green plus or red cross button in the Groups window respectively.
Use the Cluster function to operate subgroups equally by defining correct, incorrect, and neutral corners and sides. Then site variables including Name, Tag, Sex, Group, and Cluster. Save and paste the animals list by selecting Export Animals.
And Import Animals in the File menu bar to replicate the animal lists for another experiment. Next, set up all systems using their corresponding ID numbers in the Setup tab. Correspond the number of addresses in the designer section to the actual number of addresses.
Then, build the experimental protocols in the Intellicage tab, using the following Module and Option tabs. Design the Experimental Structures in the module space by clicking the Module tab. To add new modules, press the Add, drag the units shown in the units part into the module space.
To make a Nosepoke Adaption Model, drag the Door unit from the Task section, Gate, and Timer units from the Utils section, and the Visit and Nosepoke units from the Events section into the module space. Link Any on the online of the Nosepoke unit to In in the Gate unit. Link Out to Close in the Gate unit.
Link Out in the Gate to Open in the Door unit. Link Out in the Gate to Activate in the Timer unit. Link Out in the Timer unit to Close in the Door unit.
Set Period as 5, 000 milliseconds, in the Timer section. Define the initial status of the doors and cages in the Options Tab. Specify all doors to be closed in the non-drinking session as the typical initial status for PP or PPR tasks.
Then, set the time schedules in the Options Tab with correspondence to the link in the Modules section. After defining the parameters, save the experimental file with clicking the Save As button. Lastly, load the experimental file, press the Start button of the controller, and monitor and visualize the current status of the system and the mice.
To implant the radio frequency identification transponders, begin by pinching and lifting the skin around the posterior part of the scapula to create a pocket. Next, douse the injection site with 70%ethanol to minimize the introduction of hair into the subcutaneous space. Then, insert the injecting needle into the skin parallel to the spine.
Eject the microchip subcutaneously and pinch the microchip through the skin to keep it in the interscapular space. Withdraw the needle slowly, and continue to pinch the area for a few seconds to provide homeostasis. Finally, return the mouse to the home cage once it has become fully ambulatory.
Subjects used here were multiple AD Models, including NLF, Mild Model, and NLGF Severer Model, and two control groups. Results indicated that performance of AD Models in Place preference reversal, was mildly impaired in young adults. However, the performance in older subjects was significantly and progressively impaired.
In regards to executive function, the Severer AD Model lacked accuracy in the last stages of the serial reaction time test. Facilitated compulsivity was observed in young adults and old subjects of the NLGF mice. Interestingly, although there was an increase in the compulsivity of the NLF mice who were young adults, in old age, it became comparable to that of the wild type mice.
While attempting this procedure, it's important to remember to continue checking the system daily, paying special attention to the condition of animals endure inside the cages. During this procedure of the metal like drug treatment can be performed in order to answer additional questions like asking the therapeutic strategies. After its development, this technique paved the way for researchers in the fields of neuroscience to explore behavioral phenotyping, or variational in biosynthetic models.
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