Mice Models

RU486 Injection Preterm Birth Model 

Treatment of pregnant mice with the progesterone receptor antagonist RU486 is successful at inducing long-living premature mice. Our data indicates that this mice model demonstrates cognitive difficulties and vulnerability to anxiety-like behavior in adulthood, as well as differences in BDNF levels at birth and adulthood. 

Alzheimer's Disease Model

5xFAD mice express APP and PSEN1 genes with five mutations that are linked to Familial Alzheimer's disease. These mutations lead to AD related phenotypes, amyloid plaques and neuron loss as well as a range of cognitive and motor deficits.

Anxiety and Depression

In human depression and anxiety, the accumulation of stressful life events has been reported to be a significant cause. In order to simulate this effect, a model of unpredictable chronic mild stress (UCMS) is used to induce depression and anxiety-like behaviors in mice.

Old Age

Mice are considered old between 18-24 months of age. Although housing mice of such an advanced age is uncommon, the lab has conducted experiments related to improving cognitive deficits that are related to old age.

Behavioral Tests

Puzzle Box

The Puzzle Box is a problem-solving test in which mice try to get into a darker section of the box. The entrance to the darker section is blocked by tasks of increasing difficulty that the mice are required to pass within a limited amount of time. This test provides a measure for higher order cognitive executive functions.

Novel Obje​​​​​ct Recognition 

Long term (24 hours) recognition memory can be assessed by comparing the level of interest shown by the mice between two objects, one that is new and the other one with which they were acquainted the day before.

Elevated Plus Maze

 The elevated plus maze is one of the most widely used tests for measuring anxiety-like behavior in mice. The test is based on the natural aversion that mice have for open and elevated areas, as well as their natural curiosity and exploration of any novel environment. The maze is elevated off the ground and consists of open and closed arms crossed in the middle perpendicularly to each other. The number of entries into the open arms and the duration spent in them is used as a measure of open-space anxiety. Increased anxiety will lead to a preference for the closed arms and reduced exploration of the open arms.

Sucrose Preference

The sucrose preference test is an indicator of anhedonia, a decreased ability to experience pleasure. Anhedonia is one of the core symptoms of depression. The mice are presented with a sweet solution and plain drinking water. Since mice are born with a natural preference for sweet tastes, a decrease in their preference for the sweet solution over the plain drinking water is a measure for depression in mice.

Morris Water Maze

This test requires the mice to rely on visual cues to navigate from starting locations at the perimeter of an open swimming arena to locate a submerged escape platform.
The Morris Water Maze is designed to test for hippocampal-dependent learning. This includes the acquisition of spatial memory and retaining spatial memory in the long term. Spatial learning is assessed over repeated trials and is evident by reduced duration in navigation to the platform over time. Reference memory is determined by preference for the platform area when the platform is absent.​

Open Field

The open field is a square shaped enclosure in which a measure can be made of exploratory behavior and general activity.
The mice have a natural aversion to open spaces that make them feel exposed. The open field test exploits that by measuring the length of time spent in the center of the arena as a measure of anxiety-like behavior. Increased anxiety will lead to a preference to avoid the center and remain in the margins of the field.

Y-Maze

Mice are driven by an innate curiosity to explore any previously unvisited areas. This can be used to assess short term memory in mice. Spatial reference memory, which is dependent on the hippocampus, can be tested by placing the mice in the maze with one arm closed off during training. After an interval, the mice should remember which arm they have not explored previously and should visit this arm more often during the test.
With a second version of the Y-Maze test, spontaneous alternations can be assessed by allowing the mice to explore all three arms which is a measure of spatial working memory. Good working memory is dependent on the prefrontal cortex, and the mice should remember the arms previously visited and choose to enter a less visited arm each time they enter one of the arms for the duration of the test.

Biological Assays

​Alongside the behavioral tests, biological tests are performed to better our understanding regarding the connection between behaviors and the biological mechanisms that are correlated with them. From PCR for analysis of DNA, RT-PCR for the analysis of RNA and gene expression, ELISA and Western Blot for protein detection, to Stereotactic surgery which allows for targeted administration of drugs or very precise electrical stimulation in live mice.

Using video tracking software, w​​e are able to track and analyze complex behaviors.