The Morris Water Maze (MWM) task is one of the most widely used tests to measure hippocampal-dependent spatial-based learning and memory. This test is affected by aging, hormonal changes, and amnesia producing as well as cognition enhancing drugs as well as genetic manipulations of genes associated with cognition. Various protocols exist for these tests, which are used depending on a plethora of variables. Some of the protocols may be too diffuse/easy and others too intense/difficult for the animal to learn. Variables include age, strain, experimental manipulation, or predisposition to stress therefore a careful study of these variables is necessary before carrying out the test.

Test Specifics: The rodent is placed in a pool of water where it must use and remember visual cues located in the room to find a platform hidden underneath the surface of the water. The task is carried out across days to determine learning. Distance swam, latency to reach the platform, and swim speed are common measures of this test. The capacity of the animal to retrieve and retain information learned or flexibility to purge and re-learn new strategies can be determined using a probe trial & reversal trial. In the probe trial the platform is taken out and the animals are allowed to swim in the pool. Time spent in the region that previously contained the platform, crossings over the platform area, and time to reach platform location or measured. The reversal trial is identical to the training trials but in this case the platform is switch to the opposite region of the pool, thus the animal has to have the cognitive flexibility necessary to re-learn the new location. A cued version of this task can also be used to measure none spatial strategies as well as visual acuity by rendering the platform visible.

This is a simple and quick screening test to assess memory retention in rodents that uses the natural tendency of animals to “feel” safe in closed, dark areas.

Test specifics: In this test the animal must learn to avoid a mild aversive stimulus by remaining in the well-lit side, of a two-chamber apparatus and not enter the dark in which it received the aversive stimulus. Note that since animals innately gravitate to darkness, the animal has to suppress this tendency through pairing the negative stimulus with the desired compartment. Animals that do not remember the aversive stimulus will cross over earlier than animals that remember. Dependent measures include the median step-through latency (latency to cross into the unsafe side) and the percentage of animals from each experimental group that cross the threshold within allocated time.

The Y-maze is a quick and useful initial test for general cognitive function. This test is based on the innate preference of animals to explore an arm that has not been previously explored (spontaneous alternations). While it is not the most specific test for memory, Y-maze function is sensitive to damage in areas such as the hippocampus, and is also disrupted by drugs that cause memory loss and manipulations to genes associated with cognition and neurodegenerative diseases such as AD. One of the major advantages is that this task can be done without food/water or environmental aversive manipulation.

Test specifics: There are two types of Y-maze testing that can be carried out:

Spontaneous alternation version - Test subjects are placed in a Y-shaped maze for 6-8 min and the number of arms entered as well as the sequence of entries is recorded and a score is calculated to determine alternation rate (degree of arm entries without repetitions) a high alternation rate is indicative of sustained cognition as the animals must remember which arm was entered last to not re-enter it.

Short-term memory version: This is a short-term memory version in which one arm of the Y maze is blocked and the subject is allowed to explore the 2 arms for 15-30 minutes. The subject is placed back into the maze from minutes to several hours, depending on the experimental manipulation and then placed back into the maze, this time with all arms open, to explore for 5 minutes. This test can also be repeated a week after the last trial with a delay time of only 2 minutes between the trials. Animals with conserved cognitive function will remember the previously blocked arm and will enter that one first on the second trial. Typically measured parameters include: first arm entered, amount of time spent in each arm, and total number of arm entries.

This is a widely used test to measure hippocampal-dependent associative learning. This test is thought to be sensitive to emotion-associated learning and therefore is a useful measure of amygdalar-hippocampal communication.

Test Specifics: Freezing response (complete lack of movement) is the innate response of rodents to fear. The animal is placed in a box containing a grid that delivers a mild aversive stimulus for 2 minutes. In the box the animal is presented with a tone (usually 80dB) (conditioned stimulus) that is paired with a mild shock (unconditioned stimulus) at the end of the trial, repeated exposures are sometimes necessary depending on the strain used. The animal is taken out and then placed in the box 24 hrs later to evaluate its learned aversion for an environment associated with a mild aversive stimulus (Context-dependent fear) by measuring freezing behavior in the absence of tone or aversive stimulus. Cued-dependent fear can be measured by placing the animal in a new box, different in color, shape etc. and presenting it with the tone as it explores the new environment; freezing behavior associated with the tone is measured.

The recognition test is based on the natural tendency of rodents to investigate a novel object instead of a familiar one as well as their innate tendency to re-start exploring when they are presented with a novel environment. The choice to explore the novel object as well as the reactivation of exploration after object displacement reflects the use of learning and (recognition) memory processes.

Test Specifics: In this task a rodent is placed in a circular open-field filled with different objects for 6 minutes. After a series of trials, at which point the animal has habituated to the configuration and properties of the different objects, some of the objects are switched from one location to another (spatial recognition); subsequently some of the objects are replaced for new ones (novel object recognition). The time spent exploring the open field (movement/inactivity) as well as number of times and length of time inspecting the objects over the different trials is calculated.

The Barnes Maze is dry maze test for spatial learning and memory. It was initially developed for rats but is now also used for mice. It has similarities to the Morris Water Maze and to the radial-arm maze task but it uses weak aversive stimulation rather than more strong aversive stimuli such as water or food deprivation.

Test Specifics: Through remembering the spatial configuration of the room rodents learn to escape from a brightly lit, exposed circular open platform surface to a small dark recessed chamber located under one of the 18 holes around the perimeter of the platform. Note that we do not yet have the equipment in the facility. Please contact the Director for details.