habituation and acquisition training in the active place avoidance arena for mouse behavioral studies

Understanding Spatial Learning in Mice Using the Active Place Avoidance Test

Active place avoidance (APA) is an effective tool to test hippocampus-dependent spatial learning in rodents1,2,3,4. During the APA task, the animal is placed on a rotating arena and is required to use visual cues to orientate themselves and avoid an aversive shock zone5. The rotation of the arena ensures that the mouse is unable to use an idiothetic approach for navigation, nor can scent marks be used, as these cues rotate on the platform while the shock zone remains stationary5. Altering the speed and direction of the arena, as well as the location of the shock zone and visual cues, allows for the re-testing of mice multiple times6,7,8. The APA offers several distinct advantages compared to the Morris water maze (MWM), one of the most widely used spatial learning tests. Importantly, mice have an aversion to swimming and find the MWM task extremely stressful9. Further, aged mice have been reported to float during the MWM task10, making it unsuitable as a spatial learning task in many instances. Further, as the MWM task requires a hidden, submerged platform for the mice to locate during testing. This necessitates the water to be opaque, which is typically achieved via the addition of white paint. Tracking and analysis of animals during behavioral tasks requires sufficient contrast between subject and surrounds, excluding certain mouse strains such as Swiss or BALB/c from being tested in the MWM. In the APA task, this issue is circumvented through the addition of black plastic under the grid.
Multiple APA paradigms have been designed to test spatial learning, demonstrating its utility as an effective behavioral tool. For example, acquisition, retention, and consolidation of spatial learning is typically accomplished by daily testing of animals that can range from 3-5 days6,7,11,12. Memory and learning are quantified by comparing the number of shocks received each acquisition day. Time to first entrance and the maximum time avoiding the shock zone are also important parameters that can be used to determine changes in learning ability during the task. Alternatively, spatial working memory can be tested by conducting a single, 30 min APA session2,13 where spatial learning is measured as within-session changes by comparing performance, such as shock number, in 5 min bins.
In this article, we describe the APA task and highlight the key features that must be considered when conducting this spatial learning test.

Author Spotlight: Investigating the Impact of Aging on Hippocampal-Dependent Spatial Learning

The Active Place Avoidance (APA) Test, an Effective, Versatile and Repeatable Spatial Learning Task for Mice

We want to examine how hippocampal-dependent spatial learning is altered with aging. We then examine how interventions, such as physical exercise, alter these cognitive outcomes. This behavioral paradigm allows us to readily examine these in the same cohort of mice.Multiple cognitive tests are available to test spatial learning in mice, most of which have been established for decades. These include the Morris water maze, the Y-maze, and the Barnes maze. Each of these have limitations, especially in relation to longitudinal testing.The main experimental challenge is to test animals in a longitudinal manner, making it difficult to accurately determine the effect of exercise interventions. Most spatial learning tests are either easily learned or are very stressful or inappropriate for disease models. By altering some key components of the active place avoidance, such as the rotational direction of the arena or the location of the shock zone, this test is able to be used multiple times.By changing the color of the arena floor, we are able to test mice with different colors, such as C57-black-6 or Swiss mice.

Habituation and Acquisition Training in the Active Place Avoidance Arena for Mouse Behavioral Studies

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Research

JoVE Journal

Behavior

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Hippocampus-dependent spatial learning in rodents has been tested using a variety of methods. These include the Morris water maze (MWM), Y-maze, and novel object location (NOL) tasks. More recently, the active place avoidance (APA) task has been developed as an alternative to these more traditional approaches. In the APA task, mice must use spatial cues placed around a rotating arena to avoid a stationary shock zone. Due to the multiple parameters that can be adjusted, the APA task has been demonstrated to be a very versatile approach. It lends itself to being used longitudinally and repeatedly for the same cohort of mice. Here, we provide a detailed protocol to successfully conduct the APA task. We also highlight alternative APA approaches that can be used to examine different components of spatial learning. We describe the data collection and analysis processes. Critical steps during the APA task are discussed to increase the likelihood of successfully conducting the test. The APA task has several advantages over more traditional spatial navigation tests. It is appropriate to use with aged mice or those with disease phenotypes such as Alzheimer's disease. The complexity of the task can be easily altered, allowing a wide range of mouse strains to be tested. Further, the APA task is suitable for testing animals that have undergone surgery or experimental interventions that may have affected motor or neural function, such as stroke or traumatic brain injury.

Here, we present a protocol for the active place avoidance test, a hippocampus-dependent spatial learning paradigm designed for rodents. Altering key parameters allows for re-testing of animals before and after treatments or over time.

Hippocampus-dependent spatial learning in rodents has been tested using a variety of methods. These include the Morris water maze (MWM), Y-maze, and novel ...