Description

This modification of the Barnes maze was originally described in the literature as a  delayed-matching-to-place (DMP) dry maze test is a variant of DMP water maze by  Steele and Morris (Steele and Morris 1999) and refined by Faizi et al (2012). 

The DMP protocol uses a well patterned Barnes Maze with 16 holes on the outer ring, 16 on the middle ring and 8 holes on the inner ring with distance of 50, 35 and 20 cm to the center of platform, respectively.

ABS tubes (Inner diameter = 52 mm, outer diameter = 60 mm) are attached to each escape hole which allows easy attach and detach of the escape tube

Documentation

Introduction

The hippocampus plays an important role in spatial navigation and memory. In neurodegenerative and neuropsychiatric diseases, the hippocampus tends to be affected leading to memory and learning deficits. Many behavioral tests are employed to assess the extent of the effect of the hippocampus on the behaviors, spatial navigation, and memory of the subjects to develop treatments and evaluate drugs.

In 1999, Steele and Morris published a paper outlining the delayed-matching-to-place (DMP) water-maze task. They suggested that the DMP water-maze dissociates components of spatial navigation and hippocampal NMDA receptors in memory by frequently updating the escape platform. They were able to conclude that the DMP task was hippocampal-dependent and the event of escaping was NMDA receptor sensitive. The capability of the water-maze DMP to assess spatial working and episodic-like learning and memory was polished by Faizi et al., 2012 in their dry-maze DMP.

The DMP maze is a Patterned Barnes Maze (PBM) that has the escape platform frequently changed during trials. The apparatus includes an elevated circular platform having 40 holes arranged across the inner, the middle and the outer rings. Each of these holes is attached to an ABS tube. Only one tube acts as an escape tube.

Apparatus and Equipment

The PBM consists of a 122 cm diameter circular platform 1.2 cm thick. The platform consists of 40 holes; 16 holes in the outer ring (50 cm from the center), 16 holes in the middle ring (35 cm from the center) and 8 holes in the inner ring (20 cm from the center). The holes are of diameter 5 cm and are attached with ABS pipes having inner diameter 52 mm and outer diameter 60 mm. The pipes are easy to attach and detach from the escape holes. One of the ABS pipe uses a 3-inch ABS plug to serve as the escape tube. It is important that the pipes used are black to minimize any chance of visual clues from interfering with the task procedure.

Training Protocol

The subjects are briefly handled for 5 days by the experimenter 1 week before the task and are placed in darkened home cages for at least one hour before the experiment. Each subject is habituated to the escape tube for 2 minutes before the first trial is initiated.

Before beginning the experiment, the apparatus including the ABS pipes and escape tube is cleaned thoroughly to avoid any stimuli from interfering with the performance of the subject on the PBM. The high overhead lighting at 1200 lux and tone noise of 2 KHz, 85 dB can be used to create aversive motivation for the subjects. Visual cues (if any) are placed on the sides of the maze. The session can be monitored and recorded using an automatic tracking and video software such as the Noldus Ethovision XT.

Tests are carried out over a period of at least 5 days, and each trial lasts 90 seconds. The subject is carried in a covered transfer box to the test area and placed in the center of the platform. After a delay of around 30 seconds, the tone noise is played, and the subject is introduced to the maze. During the test session, the experimenter stays outside the test area to avoid influencing the subject’s behavior. The experiment ends when the subject has entered the escape tube. If the subject fails to find the escape tube after 90 seconds have elapsed, the experimenter gently nudges the subject towards the escape tube. The subject is allowed 10 seconds within the escape tube, after which the escape tube is detached, covered and the subject is put back in its home cage.

For the trials conducted over the days 2 to 4, the escape tube’s location is changed for each test day, and the trials are repeated as mentioned earlier.

Evaluation of working memory errors in mice with Closed Head Injury 

Young (3 months) and old (18 months) mice are observed on the PBM after receiving closed head injury. Both the young and old mice showed similar performances on the maze for days 1 and 2. However, the performance of the old mice deteriorated with each trial on days 3 and 4. In comparison, the sham group showed progress in their learning ability while the performance of the closed head injury group indicated working memory deficit (Feng et al., 2017).

Evaluation of CSF-1R blockade in preventing fractionated WBI-induced memory deficits

Young adult C57BL/6J mice treated with three fractions of 3.3 Gy whole-brain irradiation were maintained on a diet supplemented with PLX5622 and tested on the PBM (Feng et al., 2016).

Evaluation of scopolamine on the performance of mice on the PBM

C57BL/6j mice are divided into two groups; one treated with saline, other with scopolamine (1 mg/kg ip), and tested for their performance on the PBM (Faizi et al., 2012).

Evaluation of Thy1-hAPP(Lond/Swe+) mouse performance on the PBM

Six-month-old male Thy1-hAPP (Lond/Swe+) mice are evaluated as a model of Alzheimer’s disease. On the PBM, the mice showed significant cognitive deficits (Faizi et al., 2012).

Sample Data

The data that can be recorded are as follows

1. Escape latency: Time taken to locate and enter the escape tube
2. Distance moved: Distance covered in the process of locating the escape tube
3. Velocity: The speed at which the subject explores the maze
4. Primary error: Number of visits to the non-escape holes before the escape tube is found

Graphs allow easy visualization and comparison of performances between different groups of the subjects.

Strengths & Limitations

Strengths

The task is an adaptation of the water-maze DMP into a dry maze task. Thus it eliminates the need for immersion of the subject into the water. The PBM allows assessment of spatial working and episodic-like learning and memory by frequently changing the position of the escape tube for each trial. The task does not require food deprivation as seen in other behavioral tasks. In contrast to the traditional Barnes Maze, the positioning of the holes in the 3 rings limits the subject from taking advantage of serial strategy, thus motivating it to use spatial strategies and utilize the extra-maze visual cues. Another variation of the classic Barnes maze, the Randomized Barnes Maze can also be used for the same purpose.

Limitations

Overtraining and handling procedures may affect reinforcing properties during the task. Ageing and single housing may also impact learning and emotion of the subject and thus impact test results. The subjects own behavioral flexibility can also influence the results. Maintenance of the housing under suitable conditions is also very important. The home cages should be protected from light as pre-exposure to the light may weaken the subject’s response.

Summary and Key Points

• The Patterned Barnes Maze is a delayed-matching-to-place (DMP) dry maze task adapted from the DMP water maze designed by Steele and Morris (1999)
• The task enables assessment of spatial working and episodic-like learning and memory
• The platform has 40 escape holes arranged in 3 rings; outer ring, middle ring, and inner ring
• The escape holes have detachable ABS pipes
• Of the 40 holes, only one hole serves as the true escape (ABS pipe is plugged)
• Unlike other tasks, the task does not require food deprivation or immersion in water
• Bright light and tone noise serves as aversive stimuli

References

Steele RJ, Morris RG. Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5. Hippocampus. 1999; 9(2):118-36.

Faizi M, Bader PL, Saw N, Nguyen TV, Beraki S, Wyss-Coray T, Longo FM, Shamloo M. Thy1-hAPP(Lond/Swe+) mouse model of Alzheimer’s disease displays broad behavioral deficits in sensorimotor, cognitive and social function. Brain Behav. 2012 Mar; 2(2):142-54.

Feng X, Krukowski K, Jopson T, Rosi S. Delayed-matching-to-place Task in a Dry Maze to Measure Spatial Working Memory in Mice. Bio Protoc. 2017 Jul 5;7(13). pii: e2389. doi: 10.21769/BioProtoc.2389.

Feng, X., Jopson, T. D., Paladini, M. S., Liu, S., West, B. L., Gupta, N., & Rosi, S. (2016). Colony-stimulating factor 1 receptor blockade prevents fractionated whole-brain irradiation-induced memory deficits. Journal of Neuroinflammation, 13(1), 215. http://doi.org/10.1186/s12974-016-0671-y