Name: automated, long-term behavioral assay for cognitive functions in multiple genetic models of alzheimer's disease, using intellicage
Uploaded: 2018-08-04T15:00:00
Description: Watch this Scientific Journal Video about Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage at JoVE.com

We thank Reiko Ando for her help in photographing materials. This research was supported by Grant-in-Aid for Exploratory Research (JSPS KAKENHI Grant Number 16K15196).

All the procedures were approved by the institutional animal care and use committee, and they were carried out according to the RIKEN Brain Science Institute&#8217;s guidelines for animal experimentation.
1. Setting Apparatus
NOTE: An overview of the automated home-cage monitoring system is shown in Figure 1. Each system (39 cm x 58 cm x 21 cm) contains one microprocessor, and four corner chambers, each of which has two water bottles and ...

<ol>
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This paper describes the method using the automated home-cage monitoring system for long-term cognitive and behavioral assays in genetically modified AD models. The most critical step is the implantation of the transponder in the appropriate position. Before performing the implantation, ensure that the expiration date of the transponder has not passed. The second important point is to check the functioning of the system daily, especially as a minor problem can subsequently become a more serious one during the study (...

The development of animal models for neuronal disease over the last decade has provided a mechanistic understanding of their basis and in order to promote the therapeutic advances1,2,3. Application of a high-throughput behavioral test battery in genetic animal models is a heuristic research tool to investigate the underlying mechanisms of human diseases and identification of drug therapies. Research test batteries adapted for long-term observation of aging and/or dementia models have traditionally forced laboratories to consume great amounts of specialized manpower and time. A home-cage monitoring system would be a cost-effective strategy as it would reduce the cost of behavioral observation by humans. Some research teams have developed automated vision-based tools that assist behavioral phenotyping of a single individual in a small home cage4,5,6. However, such methods limit the social interaction, the size of testing environments, and the variety of behavioral measures that include cognitive functions. The IntelliCage is a second-generation home-cage monitoring system designed to perform various cognitive tasks in a social home cage. Importantly, this method can eliminate daily handling that enables us to perform long-term behavioral monitoring with assessment of cognitive functions, and it can eliminate the requirements for specialized practical handling, and enable highly reproducible data acquisition7. Here, we describe the long-term phenotyping and validation in genetic mouse models of Alzheimer&#39;s disease (AD) which has been generated recently8,9,10 using the automated home-cage monitoring system. A test battery, which included assessments of spatial learning and executive functions, was repeatedly performed at multiple age points (9&#8211;12 and 14&#8211;17 months old). This age-dependent phenotyping allowed us to identify the transient and/or permanent effects of genes on various cognitive aspects. We found that some AD models showed both transient and permanent phenotypes of several cognitive aspects tested in the long-term analysis using the automated home-cage monitoring system10. Thus, the automated study using home-cage monitoring system is beneficial and cost-effective for long-term behavioral phenotyping and validation in various models of cognitive dysfunction.

<table>
	<tbody>
		<tr>
			<td>IntelliCage</td>
			<td>TSE Systems</td>
			<td>-</td>
			<td>Parchased in 2011 or later</td>
		</tr>
		<tr>
			<td>PC</td>
			<td>Dell</td>
			<td>Inspiron 580s</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Display</td>
			<td>Dell</td>
			<td>SI75T-WL</td>
			<td>-</td>
		</tr>
		<tr>
			<td>ALPHA-dri</td>
			<td>Shepherd Specialty Papers</td>
			<td>-</td>
			<td>Standard bedding</td>
		</tr>
		<tr>
			<td>Aron Alpha (Krasy Glue) 2g</td>
			<td>Toagosei (Krasy Glue)</td>
			<td>#04612</td>
			<td>Cyanoacrylates for gluing magnet and blak arm</td>
		</tr>
		<tr>
			<td>Handheld Transponder Reader</td>
			<td>BTS-ID</td>
			<td>R-560</td>
			<td>Transponder reader, which reads both Trovan and DataMars</td>
		</tr>
		<tr>
			<td>Transponder</td>
			<td>DataMars</td>
			<td>T-VA, T-VAS, or another series</td>
			<td>Basic package of transponders and implanters</td>
		</tr>
		<tr>
			<td>Diamond Grip Plus</td>
			<td>Ansel Microflex</td>
			<td>DGP-INT-M</td>
			<td>Experimental glove</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Pfizer</td>
			<td>1119701G1092</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Vaporizer for small animals</td>
			<td>DS Pharma Biomedical</td>
			<td>SF-B01</td>
			<td>Facemask included</td>
		</tr>
		<tr>
			<td>Neo-Medrol</td>
			<td>Pfizer</td>
			<td>006472-001</td>
			<td>Eye ointment</td>
		</tr>
		<tr>
			<td>Ethanol (70%)</td>
			<td>-</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Excel</td>
			<td>Microsoft</td>
			<td>00202-51382-15524-AA928</td>
			<td>For data analysis</td>
		</tr>
	</tbody>
</table>

automated, long-term behavioral assay for cognitive functions in multiple genetic models of alzheimer's disease, using intellicage

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive decline, such as Alzheimer&#39;s disease (AD), have become a promising tool to elucidate the underlying mechanisms and promote the therapeutic advances. An important step is the validation and characterization of expected behavioral abnormality in the models, in the case of AD, cognitive decline. The long-term behavioral investigations of laboratory animals to study the effect of aging demand substantial efforts from researchers. The IntelliCage system is a high-throughput and cost-effective test battery for mice that eliminates the need for daily human handling. Here, we describe how the system is utilized in the long-term phenotyping of a genetic Alzheimer&#39;s disease model, specifically focusing on the cognitive functions. The experiment employs repeated battery of tests that assess spatial learning and executive functions. This cost-effective age-dependent phenotyping allows us to identify the transient and/or permanent effects of genes on various cognitive aspects.

In our previous study, the age-dependent cognitive deficits in AD models were detected by the experiments using the automated home-cage monitoring system10. Their performance of AD models in PP was intact in both young adults and older subjects; however, the performance in PPR was significantly and progressively impaired (Figure 6). It is also important to observe the general behavior or anxiety in the adaptation phase because such tra...

Watch this Scientific Journal Video about Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage at JoVE.com

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

This paper describes a protocol for cognitive assessments for genetic models of the Alzheimer&#39;s disease using the IntelliCage system, which is a high throughput automated behavioral monitoring system with operant conditioning.

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive ...

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