Cognition

CIRCULAR (MORRIS) WATER MAZE

The (Morris) Water Maze tests Spatial Memory. The water maze consists of a pool, with a hidden platform submerged just below the water surface. Over a period of days (trials), the mouse learns to escape from the water by locating the platform with the help of visual cues located on the walls outside the maze. In a second phase of the experiment, the platform is removed altogether, or placed in another quadrant, to investigate the animal’s perseveration or cognitive flexibility i.e. how quickly it can learn that the platform is not in the original location.  The animal behavior is recorded and analysed using video tracking with Ethovision 8.5XT software. Several parameters can be analysed to measure performance such as

  • Latency to reach the platform.
  • Average distance to platform: Gallagher’s proximity.
  • Total distance swum until reaching the platform.
  • Total percentage of time spent in specific quadrant.
  • Mean swimming velocity.
  • Direction of movement relative to the platform (heading).
OBJECT AND SPATIAL RECOGNITION TASKS

The novel object recognition task assesses the ability of mice to recognize a novel object in an otherwise familiar environment and is a relatively simple method to assess working memory and spatial navigation. In the novel object recognition test, the interest of an animal for a novel object versus a familiar one is measured and compared. The time spent investigating an object is recorded then following a brief period of time back in the home cage the mouse is returned to the arena where a novel object and the original object are now present.  The time spent investigating both objects is recorded.  If the exploration of the novel and the familiar object is equal, this may be interpreted as a memory deficit since one would expect the mouse to investigate the novel object in preference to the familiar one.  The animal behavior is recorded and analysed using video tracking with Ethovision 8.5XT software.

WATER T-MAZE DELAYED ALTERNATION

Delayed alternation refers to the alternation of rewards, especially in maze learning, where a delay is implemented between trials. This requires the subject to alternate their responses in order to gain the reward. It is thought to depend on an intact hippocampus and is  a function of working memory.  Testing occurs in a T-shaped maze filled with water. This test is used to quantify cognitive deficits in transgenic strains of mice and evaluate novel chemical entities for their effects on cognition.
CONTEXTUAL FEAR CONDITIONING 
This paradigm is widely used to assess hippocampal and amygdala-dependent learning and memory performance in rodents. Briefly, it consists of exposing the animals to an operant conditioning chamber (same as for operant conditioning) for 5 minutes and in which they will receive an aversive stimulus (AS). This negative reinforcement procedure is necessary to assess the ability of mice to associate a specific context with an unpleasant experience. This stimulus is not harmful  nonetheless the general health status of the animals will be monitored immediately after the training session and prior to the testing session the next day.  Twenty-four hours after the training session, the animal is put back in the operant chamber for three minutes (no AS is delivered during this session) and the percent time spent freezing is recorded. The freezing response is here used as a surrogate marker of memory performance as animals remembering the AS during the training session are expected to spend a significant amount of time freezing during the retention session.

HOLEBOARD

The holeboard can be used to measure simple exploration or it can be used as a simple measure of attention.  The arena consists of a perspex box with a floor that contains shallow holes.  To measure exploration the mouse is placed in the arena at one side and allowed time to explore.  The number of holes visited, time spent sniffing and distance travelled around the arena are measured.  For a simple measure of attention, the mouse is placed in the holeboard on 4 separate days and the same measurements of exploration taken.  On Day 5, one of the holes is baited with an inanimate object and the mouse once again placed in the arena.  If the mouse has a normal attentional capacity it will notice the object is new and direct its exploration to that hole and therefore the amount of time spent investigating will be greater than the previous day.

SOCIAL RECOGNITION is specific study of memory utilising social behavior as the functional output. This test is conducted in a three-chambered test apparatus. To test recognition, the two wired cages contain a familiar and an unfamiliar conspecific. In most cases the interest is measured by assessing the time spent in the same chamber or in close proximity to the familiar or unfamiliar other mouse. The Noldus sociability cage (40.5 x 60.0 x 22.0 cm) is especially designed for automated video tracking with EthoVision®XT. It is made out of clear acrylic walls and has interchangeable floors (white or coloured), making the cage suitable for tracking of both light and dark mice. The apparatus also  includes two removable clear acrylic slide doors to prevent access to the side chambers, and two small acrylic cages (10 cm diameter x height 20 cm) for the introduction of the stranger mice. A small space between the chambers allows you to slip a piece of paper between the chambers in order to prevent visual contact between the three chambers.

Noldus sociability cage