Radial Arm Maze

Specifications (Mouse)

Specifications (Rat)

The Radial Arm Maze (RAM) is one of the most widely used behavioral tasks in neuroscience. It was originally designed by Olton and Samuelson in 1976 to understand spatial learning and memory in rodents. It was observed that rodents have a remarkable ability to remember spatial locations, especially when baited with food rewards, and this ability was adapted into a behavioral task. Radial Arm Maze was developed based on the fact that finding and retrieving food quickly and efficiently served as an essential survival strategy for rodents.

The hippocampus plays a vital role in the consolidation of short-term memory to long-term memory, spatial cognition, emotional behavior, learning and regulation of hypothalamic functions. The complex structure is one of the unique brain regions that see neurogenesis continue into adult life and is vulnerable to damage by a variety of stimuli. Studies have also shown the hippocampus to be affected in a variety of neurological (such as Alzheimer’s) and psychiatric disorders (such as PTSD, Schizophrenia) (Anand & Dhikav, 2012). Therefore, behavioral tasks, such as Radial Arm Maze, assist in gaining insight into hippocampal-dependent functions and effect of hippocampus damage and atrophy.

The original design of Radial Arm Maze consisted of a 34 cm wide central platform with eight equal-length arms radiating out and was initially used to observe spatial learning and memory in rodents. Recent adaptations of the maze, however, no longer limit it to the assessment of spatial learning and memory and allow concurrent investigation of working and reference memory. RAM task requires the use of hippocampal-dependent spatial reference memory, and this ability to remember the location of visited arms can be affected by the administration of certain substances or disease models. Variations of the maze have been used in research involving birds, insects, and even humans.

Origin

The first use of Radial Arm Maze was recorded in 1976 by Olton and Samuelson who used it to demonstrate the efficiency and memory of rodents in choosing an average of more than seven different arms in the first eight choices. It has since been extensively used in behavioral neuroscience research for its ability to measure working and reference memory, its many variations, and for its minimally stressful environment.

Developments

Olton published a series of papers describing the maze and evaluation of hippocampal-dependent learning over several years (Olton and Samuelson 1976, Olton et al., 1977, Olton and Collison 1979, Olton 1987). Since these initial papers, the maze has been used to study various neurological issues, such as brain injuries, hippocampal lesions, depression, and even the effects of electromagnetic fields emitted from cellular phones on memory deficits (Dubreuil et al., 2003).

Recent Developments

The task apparatus has also seen various modifications over the years to include different cues (such as light cues), flexible arms (3D Radial Arm Maze), environments (Water model) and a variable number of arms, to list a few. The apparatus has also been adapted to be used with other subjects such as insects (Elizabeth et al., 2016), and humans (Mennenga et al., 2014).

Harvey et al. assessed the impact that Anterior Thalamic Nuclei (ATN) lesions have on spatial working memory performance. Unlike the previous studies, this investigation aimed to investigate lesion’s effect in a discriminate task variant by testing the animals before and after inactivation of the ATN. The results demonstrated clear deficits in spatial discrimination in the Radial Arm Maze following inactivation of the ATN.

The effect of (CIE) exposure was studied by Risher et al. in adolescent and adult rats. The study investigated the long-term effects of CIE on spatial memory and cognition and found that CIE during adolescence renders the animal more susceptible to memory disrupting effects of acute ethanol well into adulthood.

An adapted human version of the Radial Arm Maze was used by Mennenga et al. to serve as a tool to connect human and rodent models of cognitive functioning. Their study evaluated human working memory and factors that contribute to the navigational ability of humans. The experiments showed that errors increased in a similar pattern as seen in a rodent model of RAM as the working memory demand increased.

The Radial Arm Maze has also seen adaptation as a computerized version wherein the subjects as tested in a virtual environment (Braun et al., 2012, Lee et al., 2014).

The Radial Arm Maze’s basic construction includes a central circular platform with the arms radiating outwards. The central platform is usually of an approximate diameter of 30 cm, and the arms tend to be approximately 80 cm long with a width of 10 cm. These measurements can be varied and adjusted depending on the experimental requirement and the subject being used. The entrances of the arms usually have doors, that is either removable or guillotine styled, to limit access. The entire apparatus, in general, is transparent to allow the subject to visualize extra-maze cues, although opaque versions are also available. The apparatus is usually raised 50 cm above the floor.

Over the years the apparatus for Radial Arm Maze has been improved upon to meet different requirements of behavioral investigations. Modifications such as adding a goal box to the end of the maze arms, water models, etc. have been made to assist the needs of investigatory processes. A fully automated Radial Arm Maze is also available, which detects the location of the animal within the maze, automates opening and closing of doors within the maze, and detects the presence of the food reward in the arm chambers.

The apparatus should be well lit from above to prevent shadows to ensure the proper utilization of Radial Arm Maze. Observation of the Radial Arm Maze task can be done using tracking software such as Noldus Ethovision XTor ANY-Maze, mounted above the apparatus. Live scoring is also possible.

The hippocampus plays a crucial role in memory, spatial memory, spatial navigation, and in conflict-avoidance decision making. In neurodegenerative diseases (such as Alzheimer’s and other forms of dementia) and neurological disorders (such as PTSD, Schizophrenia, depression, etc.), hippocampal disruption is usually observed. Hippocampal abnormalities or damaged hippocampus greatly impact cognitive abilities and memory and thus require a more in-depth investigation into the development of successful drug treatments.

Epilepsy Medications

Koh et al. tested the benefit of Epilesy medications on memory performance of “K” exposed adult rats, in a preclinical model of schizophrenia. The substance showed a dose-dependent improvement in memory performance of the “K” treated rats. Repeated ANOVA also indicated a significant within-subject effect. The study suggested the use of Epilepsy therapeutics has the potential dual benefit of ameliorating cognitive impairment and attenuating positive symptoms of schizophrenia.

ADHA Medications and Ethanol

Studies that suggested the misuse of ADAH medication and Ethanol prompted Sloan et al. to examine the potential effects of co-abuse on working and reference memory. A significant overall working and reference memory impairment was observed for the combination of ADAH medication and Ethanol at both the 0.75 mg/kg and 1.5 mg/kg of ADAH medication in comparison to other conditions. Researchers concluded that working memory deficits caused by Ethanol are made worse by concomitant ADAH medication injections, suggesting that memory is particularly susceptible to co-abuse of both substances.

MPD is one of the most commonly prescribed drugs for Attention-deficit hyperactivity disorder (ADHD), for children and adolescents. Dow-Edwards et al. conducted an invasive investigation of effects of MPD in periadolescent rats to demonstrate its effects on cognitive processes. Subjects were administered MPD (1 or 3 mg/kg/day) via gastric intubation from postnatal day 22 to 59 and assessed for their drug-related performance on the radial arm maze each day. Results of the study suggested that 3 mg/kg oral MPD improves performance on a spatial cognitive task only early in treatment in the rat and that motivation plays a crucial role for females to show the effects of MPD. Male rates showed improvements regardless of the level of motivation.

Antidepressants

Akar et al. investigated the effects of PDE 4 and PDE 5 inhibitors on learning and memory of male mice. The subjects were acutely treated with PDE 4 inhibitors (0.05 and 0.1 mg/kg) and PDE 5 inhibitors (3 and 10 mg/kg) before the retention trial of radial arm maze test. Subjects treated with Zaprinast (3 and 10 mg/kg) showed a significant decrease in errors in the retention trial as compared to Rolipram.

Antipsychotics

Effects of atypical antipsychotics were investigated in naïve mice, and MK-801 treated mice by Multu and colleagues in 2012. When administered, “O” (0.4, 0.8 and 1.25 mg/kg, i.p.) and “C” (0.5 and 1 mg/kg, i.p.) they potently reversed MK-801 induced increase of working memory errors while the MK-801-induced enhancement in the speed was blocked by “O” but not “C”. The study showed the potential of these antipsychotics in improving cognitive deficits in schizophrenic patients.

Anti-obesity and Anti-Dementia Substances

Enhancing effects of “R” and “D”on learning and memory in rodent models have been demonstrated individually, but their combined effect was demonstrated by Wise et al. The trials were performed using a delay Radial Arm Maze at different doses of the drugs individually and finally in combination. It was observed that sub-threshold doses of the CB1 receptor antagonist “R” (0.3 mg/kg) and the AChE inhibitor “D”  (0.1 mg/kg) significantly enhanced memory as assessed in a rat delay radial-arm maze task. It was further observed that the same doses when administered individually did not emulate the same results.

MLA

A 2001 study conducted by Bettany et al., investigated the effects of chronic nicotine administration on memory performance of rats treated with nicotinic α7 antagonists MLA. MLA doses of 14.64 and 43.92 microgm/side in rats not treated with nicotine showed significant memory impairment which could not be blocked by chronic systematic nicotine exposure. The results highlighted the importance of ventral hippocampal α7 receptors in memory function and its disruption on the effectiveness of systematic nicotine treatment.

The purpose of the Radial Arm Maze is to assess spatial memory and spatial learning in animals, in control vs. disease model/intervention group, by observing their ability to navigate the arms of the maze and remember which arms they have previously entered. Typically, animals are capable of learning and remembering the location of arms with food rewards using visual cues.

This test can provide information regarding hippocampal-dependent learning, specifically spatial memory. For example, the effects on memory abilities in animal models of aging (Shukitt et al., 2004) or neurodegenerative diseases can be tested using the Radial Arm Maze. Learning and remembering are essential to survival strategy and tends to get impacted in subjects with impaired neuro-cognitive abilities. As the aptitude to remember decreases, the subject’s task errors increase, and the subject tends to make multiple re-entries into the arms.

Several protocols exist for Radial Arm Maze depending on the experimental aim, and the data researchers are looking to obtain. The most common protocol, used in the study of hippocampal lesions or degeneration and to determine the involvement of a specific gene or protein in spatial memory, uses a fully baited version of Radial Arm Maze wherein the subject is required to visit each arm only once per trial.

Pre-Training for the Fully-Baited Radial Arm Maze

Pre-training sessions can be done across several days prior to the experiment. Subjects are placed in small groups on the maze and allowed to explore the maze for 20 minutes freely. The maze floor is scattered with food rewards to encourage the subjects to explore. On the subsequent days, food rewards are only placed at the ends of the arms. For tasks involving automated Radial Arm Maze, the subjects are also familiarized with the movements and noise of opening and closing of the automated doors.

Evaluation of Spatial Learning and Memory Using the Radial Arm Maze

Training and testing processes begin with cleaning the apparatus to minimize olfactory cues and setting up of any visual cues within the test areas. Food rewards are placed in the chambers at the end of each arm. For tasks involving automated Radial Arm Maze, doors to each of the arms are closed. The subject is brought into the room and placed on the central platform and allowed an acclimate, if necessary.

For the fully-baited training procedure, subjects are tested over the course of 10 to 20 consecutive days. Each arm chamber consists of a food reward, and the subject is expected to learn to visit each arm only once per session. The session is terminated when the subject has visited all 8 arms and has eaten the reward after 16 arm visits are made (regardless of which arms) or after a maximum of 15 minutes. For the automated Radial Arm Maze task, the subject is placed on the central platform, and the doors are opened simultaneously to allow the subject to explore.

Subject’s reference memory can also be tested by baiting some of the arms while the remaining arms remain un-baited. The session is terminated when eight minutes have passed or until all baited arms are entered. A repeated entry into a baited arm is counted as a working memory error while any entry into an un-baited arm is recorded as a reference memory error.

Since the introduction of the Radial Arm Maze by Olton and Samuelson in the mid- 1970’s, researchers have adapted the Radial Arm Maze to meet the various requirements of the investigatory process of spatial learning and memory. While each modification allows for the collection of specific data and can help differentiate between working and reference memory, the different versions of the Radial Arm Maze all provide measures of the spatial learning, memory, and overall cognitive function.

Like the fully-baited Radial Arm Maze task, there is also a confinement/delay version of the maze. In this task when the subject enters an arm, it interrupts the infrared beam which triggers the automatic closure of the remaining doors. Once the subject returns to the central platform, the eighth door is also closed, and the subject is confined to the center for 10 seconds. After the completion of the delay, all doors are opened simultaneously, and the same procedure is repeated. (Dubreuil et al., 2003) Longer delays have also been utilized in other research, to test how long the subject can remember spatial locations (Suzuki et al., 1980, Bolhuis et al., 1986, Strijkstra et al., 1987).

Another version of Radial Arm Maze uses a setup that is not fully baited. The trial session is comprised of three phases: a training phase, a delay phase, and a test phase. For the training phase, four arms are randomly chosen and baited with food rewards while the access to the remaining four was blocked by the doors. The subject can explore the baited arms and retrieve the food rewards for approximately 5 minutes. Once the subject has retrieved all the food rewards and returned to the center, all the arms are closed, and the subject is isolated in the center platform for either 30 second or 15 minutes depending on the experimental design. After the delay, all the arm doors are simultaneously opened, and the test phase is initiated. During this phase the previously blocked, un-baited arms are baited with food rewards and the subject is expected to visit the arms that it had not visited in the training phase. The test phase begins with opening the doors and allowing the subject to retrieve the food rewards. The test is concluded when the last food reward is retrieved, or 300 seconds have expired. This version of the Radial Arm Maze has been used to study cognitive dysfunction and its relationship to depression-like symptoms. (Richter et al., 2013)

The Water Radial Arm Maze was developed to overcome the shortcomings of the dry land version of the maze. The water-based model, in contrast to the land-based model, does not require food deprivation, minimizes the influence of scent cues and utilizes the subject’s motivation for escape as an effective means to assess the working and reference learning and the memory simultaneously without the need for pre-training. For the water-based Radial Arm Maze task, the RAM apparatus is placed in a pool of water, and four arms are baited with an escape platform. The trial begins by placing the subject in the start arm, facing the wall. The subject can explore the maze for a maximum of 120 seconds or until it has reached one of the escape platforms. Subsequent trials progress by the removal of the visited escape platform. A record of all the visited arms, remaining platforms and visited platforms is maintained to correctly measure the reference memory and the working memory of the subject. (Penley et al., 2013)

The 3-D Radial Arm Maze is a modified version of the Radial Arm Maze developed by Abdel Ennaceur in 2006. Ennaceur’s 3D radial arm maze became a groundbreaking venture because of the unique design; the subjects exposed to unfamiliar open spaces without a safe alternative. The maze utilizes open spaces and spatial navigation both horizontally and vertically. Flattened, Raised, and lowered arms allow for a high degree of flexibility in various experiments.

A combination of the classic Radial Arm Maze and Barnes Maze, the Radial Arm Barnes Maze combines the advantages of both the mazes into one. The maze was first described by Paganelli’s et al. in their 2004 paper investigating influence of ischemic brain damage on acquisition and retention of cognition in mice.

A common modification of the Radial Arm Maze is varying the arm lengths or the number of arms. The Arm Length variant RAM and the n-Arm variants RAM allow evaluating the effects of changing the lengths and number of the arms on the spatial and memory performance of the subjects.

The data obtained from the Radial Arm Maze generally consists of following measures:

• Number of total arm entries (the animal places all four paws in an arm)
• Number of correct arm entries (the animal enters a novel arm not previously entered)
• Number of error arm entries (the animal enters an arm previously entered or enters an un-baited arm)

The time between retrieving food rewards can also be recorded as a measure of activity and willingness to explore. As the animal learns that entering a new arm results in a food reward, the number of error arm entries is expected to decrease. These values can merely be graphed and compared to a sham control group and a disease model/intervention group.

In addition to counting entries, a memory score can also be calculated.

This score describes the memory performance on a scale from -1 to 1, with a score of 1 reflecting a perfect score of only entering novel arms (Richter et al., 2013). Memory scores are likely to improve over several tests.

Graphs allow easy visualization of comparisons of the effect on spatial memory and learning between different disease or treatment groups. Control groups are usually expected to show significant improvements in their correct arm entries and memory scores while subjects in disease models of neurodegenerative disorders, for example, should show a much slower learning curve with more error entries, even after several trials. Generally, animal cohorts of 20-30 animals are sufficient to obtain p-values of <0.05 using ANOVA, chi-squared test, and post-hoc tests (Dubreuil et al., 2003, Richter et al., 2013)

Radial Arm Maze has also been adapted into a human model to act as a translational instrument in comparison of existing methodologies in rodent and human learning and memory research (Mennenga et al., 2014). The results of the research showed a significant correlation in error patterns seen in rodent-based models and the human-based model, as the working memory demand increased.

Genetic animal models employing delayed spatial win-shift task have shown high translational potential for the study of cognitive dysfunction (Richter et al., 2013). The model used two strains of rats: Congenitally helpless rats and rats resistant to helplessness, and tested them using Radial Arm Maze procedures used by Olton et al. and also with imposed temporal delay at some time within the sequence of arm visits. Congenitally helpless rats were shown to have impaired affective processing similar to depressed patients.

The growing use of mobile phones has rejuvenated interest in electromagnetic field research to understand the effects of electromagnetic fields (EMF) in humans. Animal models allow more detailed and invasive investigations that are complementary to human studies. Experiments carried out by Dubreuil et al., tested rats exposed to 45-min head-only exposure to 900 MHz GSM EMF in an automated Radial Arm Maze task and found no evidence to support the effect of EMF on spatial and non-spatial memory.

The Virtual Radial Arm Maze challenges the participant’s place learning skills, allowing assessment of their capacity to discriminate, remember and process the information as they explore the maze. The Radial Arm Maze can be easily adapted and modified to limit the use of certain strategies by the participants. Using inter-trial delays can also aid in the investigation of the memory capabilities of the participants. The absence of significant stressors and familiarization with the maze before testing allows for better observations of working and reference memory of the participants.

Radial Arm Maze was developed to allow place learning which was, in models before it, seen as a factor that needed to be controlled. By utilizing the subject’s place learning skills, researchers can assess the capacity of the subject to discriminate, remember and process information as it explores the maze (Olton et al., 1976).

In contrast to other mazes, Radial Arm Maze does not utilize aversive stimulus to test spatial learning as seen in Morris Water Maze that requires the animals to be submerged in water and swim in order to survive by searching for an escape platform (Hodges 1996). The Radial Arm Maze also allows the use of food rewards as task motivation, rather than using escape and survival reinforcers, which intrinsically places less stress on the animals (Hodges 1996). The absence of significant stressors and familiarization with the maze prior to testing allows for better observations of working and reference memory in the animals as they perform in the maze.

The RAM assists in repeated measures of detecting steady-state reference and working memory deficits, although this does require precise analysis (Hodges 1996). Additionally, RAM can be modified to limit the use of particular strategies by limiting route choices using doors to block off arms. Doors can also be used to create novel arms that can be revealed in the subsequent trials. Automation of the apparatus is also helpful in creating triggered delays (Dubreuil et al., 2003) to test how long the subject can remember spatial locations. The Radial Arm Maze can also be modified to complement the specific needs of the study/ experiment, such as using a water environment for a task trial (Shukitt et al., 2004). In many cases, the Radial Arm Maze is used in conjunction with other mazes to study disease models or transgenic animals and gain a fuller understanding of spatial learning and memory.

As with all mazes that measure aspects of learning and memory, it is important to remember that many different processes affect the behavior of the subject in the maze. Overtraining of the subject and the subject’s preferred behavioral response can impact the test results. It should also be kept in mind that the Radial Arm Maze requires more training and is more time-consuming than other mazes used for similar measures.

• The Radial Arm Maze is extensively used to test spatial learning and memory.
• RAM task asks animals to retrieve food rewards at the end of each of eight arms without visiting an arm more than once.
• Different groups have adapted this maze in order to collect data regarding working or reference memory, and there are many modifications available, both regarding experimental protocol and data analysis.
• Animals in control groups show rapid learning as they remember the location of the arms from which they have retrieved the food reward, while in comparison, animals as disease models of neurodegenerative disorders or brain injuries show a much slower learning curve with lower memory scores.

Akar F, Mutlu O, Celikyurt IK, Ulak G, Erden F, Bektas E, Tanyeri P. (2015) Effects of “r” and “z” on learning and memory in the Morris watermaze and radial arm maze tests in naive mice. Drug Res (Stuttg). 65(2):86-90. doi: 10.1055/s-0034-1372646

Anand KS, Dhikav. (2012) Hippocampus in health and disease: An overview. Ann Indian Acad Neurol. 15(4):239-46. doi: 10.4103/0972-2327.104323.

Bettany JH, Levin ED. (2001) Ventral hippocampal alpha 7 nicotinic receptor blockade and chronic nicotine effects on memory performance in the radial-arm maze. Pharmacol Biochem Behav. 70(4):467-74.

Bolhuis, J.J., Biljlsma, S., Ansmink, P. (1986) Exponential decay of spatial memory of rats in a radial maze. Behav. Neural Biol. 46, 115-122

Braun, J. M., Lucchini, R., Bellinger, D., Hoffman, E., Nazzaro, M., Smith, D. R., & Wright, R. O. (2012)  Predictors of virtual radial arm maze performance in adolescent Italian children. Neurotoxicology, 33(5), 1203–1211. http://doi.org/10.1016/j.neuro.2012.06.012

Dow-Edwards DL1, Weedon JC, Hellmann E. (2008) “M” improves performance on the radial arm maze in periadolescent rats. Neurotoxicol Teratol. 30(5):419-27. doi: 10.1016/j.ntt.2008.04.001

Dubreuil D, Jay T,  Edeline J. (2003) Head-only exposure to GSM 900-MHz electromagnetic fields does not alter rat’s memory in spatial and non-spatial tasks. Behav Brain Res. 145(1-2):51-61.

Dubreuil, D., Tixier, C., Dutrieux, G., Edeline, J.M. (2003) Does the radial arm maze necessarily test spatial memory? Neurobio. Learning Memory 79, 109-117

Dudchenko, P.A. (2004) An overview of the tasks used to test working memory in rodents. Neurosci. and Behav. Reviews 28, 699-709

Forman, N. Ermakova, I. (1998) The radial arm maze: twenty years on. In: A handbook of spatial research paradigms and methodologies. Hove Psych. Press, 87-144

Harvey RE, Thompson SM, Sanchez LM, Yoder RM, Clark BJ. (2017) Post-training Inactivation of the Anterior Thalamic Nuclei Impairs Spatial Performance on the Radial Arm Maze. Front Neurosci. 11:94. doi: 10.3389/fnins.2017.00094.

Hodges, H. (1996) Maze procedures: the radial-arm and water maze compared. Cog. Brain Research 3, 167-181

Koh MT, Shao Y, Rosenzweig-Lipson S, Gallagher M. (2017) Treatment with “l” improves cognition in a ketamine rat model of schizophrenia. Schizophr Res.  pii: S0920-9964(17)30366-3. doi: 10.1016/j.schres.2017.06.027.

Lee JY, Kho S, Yoo HB, Park S, Choi JS, Kwon JS, Cha KR, Jung HY. (2014) Spatial memory impairments in amnestic mild cognitive impairment in a virtual radial arm maze. Neuropsychiatr Dis Treat. 10:653-60. doi: 10.2147/NDT.S58185.

Mahmmoud RR, Sase S, Aher YD, Sase A, Gröger M, Mokhtar M, Höger H, Lubec G. (2015) Spatial and Working Memory is Linked to Spine Density and Mushroom Spines. PLoS One. 10(10):e0139739. doi: 10.1371/journal.pone.0139739

Mennenga SE, Baxter LC, Grunfeld IS, Brewer GA, Aiken LS, Engler-Chiurazzi EB, Camp BW1, Acosta JI, Braden BB4, Schaefer KR, Gerson JE, Lavery CN, Tsang CW, Hewitt LT, Kingston ML, Koebele SV, Patten KJ, Ball BH, McBeath MK, Bimonte-Nelson HA. (2014) Navigating to new frontiers in behavioral neuroscience: traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze. Front Behav Neurosci. 8:294. doi: 10.3389/fnbeh.2014.00294

Mutlu O, Celikyurt IK, Ulak G, Tanyeri P, Akar FY, Erden F. (2012) Effects of “o” and “c”e on radial maze performance in naive and MK-801-treated mice. Arzneimittelforschung. 62(1):4-8. doi: 10.1055/s-0031-1291360

Nozari M, Mansouri FA, Shabani M, Nozari H, Atapour N. (2015) Postnatal MK-801 treatment of female rats impairs acquisition of working memory, but not reference memory in an eight-arm radial maze; no beneficial effects of enriched environment. Psychopharmacology (Berl). 232(14):2541-50. doi: 10.1007/s00213-015-3890-5

Olton, D.S. (1987) The radial arm maze as a tool in behavioral pharmacology. Physio. and Behav. 40, 793-797

Olton, D.S., Collison, C. (1979) Intramaze cues and “odor trails” fail to direct choice behavior on an elevated maze. Animal Learning and Behav. 7, 221-223

Olton, D.S., Collison, C., Werz, M.A.. (1977) Spatial memory and radial arm maze performance of rats. Learning and Motivation 8, 289-314

Olton, D.S., Samuelson, R.J. (1976) Remembrance of places passed: Spatial memory in rats. J. Exper. Psych. Animal Behav. Processes 2, 97-116

Penley SC, Gaudet CM, Threlkeld SW. (2013) Use of an eight-arm radial water maze to assess working and reference memory following neonatal brain injury. J Vis Exp. (82):50940. doi: 10.3791/50940.

Richter, S.H., Zeuch, B., Lankisch, K. Gass, P., Durstewitz, D., Vollmayr, B. (2013) Where have I been? Where should I go? Spatial working memory on the radial arm maze in a rat model of depression. PLOS One 8, e62458

Risher ML, Fleming RL, Boutros N, Semenova S, Wilson WA, Levin ED, Markou A, Swartzwelder HS, Acheson SK. (2013) Long-term effects of chronic intermittent ethanol exposure in adolescent and adult rats: radial-arm maze performance and operant food reinforced responding.  PLoS One. 8(5):e62940. doi: 10.1371/journal.pone.0062940

Shukitt-Hale B, McEwen JJ, Szprengiel A, Joseph JA. (2004) Effect of age on the radial arm water maze-a test of spatial learning and memory. Neurobiol Aging. 25(2):223-9.

Sloan AR, McGovern R, Buffalari DM. (2016) Effects of concomitant “m” and ethanol administration on working and reference memory in rats. Pharmacol Biochem Behav.150-151:134-137. doi: 10.1016/j.pbb.2016.10.009. Epub 2016 Oct 26.

Strijkstra, A.M., Bohuis, J.J. (1987) Memory persistence of rats in a radial maze varies with training procedure. Behav. Neural Biol. 47, 158-166 (1987).

Suzuki, S., Augerinos, G., Black, A.H. (1980) Stimulus control of spatial behavior on the eight-arm maze in rat. Learn Motiv 11, 1-18

Wise LE, Iredale PA, Stokes RJ, Lichtman AH. (2007) Combination of “r” and “d” prolongs spatial memory duration. Neuropsychopharmacology.1805-12.

Paganelli RA, Benetolli A, Lima KC, Cestari-Junior LA, Favero Filho LA, Milani H. A novel version of the 8-arm radial maze: effects of cerebral ischemia on learning and memory. J Neurosci Methods. 2004 Jan 15;132(1):9-18.

Animal-based models have often been used to allow for a more invasive investigation of the underlying causes in transgenic/disease models and in testing drug effects. Adaptability and modifiability of the RAM to the specific needs of experiment and testing makes it one of the popular behavioral tasks. Subjects with impaired cognition are likely to make more reference and working errors in the RAM when compared to control groups.