Assessment of Spatial Memory

Gary L. Wenk1

1 University of Arizona, Tucson, Arizona
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 11.3
DOI:  10.1002/0471140856.tx1103s00
Online Posting Date:  May, 2001
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Abstract

Behavioral tasks must be evaluated in terms of the cognitive functions they require. The tasks described in this unit are useful for detecting stimulation by drugs or a small electrical current, impairment of normal function by production of lesions or administration of a pharmacologic or toxicologic agent, recording activity during performance of a specific task, or behavioral phenotyping of transgenic or knockout mice. The radial arm maze test is used for basic working memory or working memory versus reference memory; the water maze task is used for spatial memory, spatial probe trials, or working memory; and the T-maze test is used for spatial memory, working versus reference memory, or spontaneous alternation.

     
 
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Table of Contents

  • Assessment of Spatial Memory
  • Basic Protocol 1: Use of Radial Arm Maze Task to Test Basic Working Memory
  • Alternate Protocol 1: Use of Radial Arm Maze Task to Test Working Versus Reference Memory
  • Basic Protocol 2: Use of Morris Water Maze Task to Test Spatial Memory
  • Alternate Protocol 2: Use of Water Maze Task for Spatial Probe Trial
  • Alternate Protocol 3: Use of Water Maze Task to Test Working Memory
  • Basic Protocol 3: Use of T Maze to Test Spatial Memory
  • Alternate Protocol 4: Use of T Maze to Test Working Versus Reference Memory
  • Alternate Protocol 5: Spontaneous Alternation a T Maze
  • Commentary
  • Bibliography
  • Figures
     
 
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Materials

Basic Protocol 1: Use of Radial Arm Maze Task to Test Basic Working Memory

 Materials
  • Rats
  • Pharmacologic or toxicologic agents (optional)
  • Food reward: e.g., 1-mg piece of normal chow, flavored (chocolate) or sweetened breakfast cereal, chocolate milk, or water
  • Radial arm maze (Fig. 11.3.1), handmade or fully automated (Coulbourn Instruments or Columbus Instruments)

Basic Protocol 2: Use of Morris Water Maze Task to Test Spatial Memory

 Materials
  • Rats
  • Pharmacologic or toxicologic agents (optional)
  • Water maze apparatus (Fig. 11.3.2)
  • Tracking system and software (Columbus Instruments, HVS Image, San Diego Instruments, or CPL Systems)

Basic Protocol 3: Use of T Maze to Test Spatial Memory

 Materials
  • Rats
  • Pharmacologic or toxicologic agents (optional)
  • Food reward: e.g., 1-mg piece of normal chow, flavored (chocolate) or sweetened breakfast cereal, chocolate milk, or water
  • Split-stem T maze (Fig. 11.3.3), handmade or commercial (Coulbourn Instruments or Columbus Instruments), without hardware cloth partition, Plexiglas barrier, or curtain

Alternate Protocol 4: Use of T Maze to Test Working Versus Reference Memory

 Additional Materials (also see Basic Protocol 3)
  • Hardware cloth partition, Plexiglas barrier, and curtain for split-stem T maze (Fig. 11.3.3)
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Figures

  •  FigureFigure 11.3.1 Eight-arm radial maze. For rats, the central platform should be ³45 cm in diameter to accommodate the animal and allow it to turn easily between arms. A Plexiglas wall, 25 cm high, surrounds the central platform. The arms are 87 cm long and 10 cm wide, radiating from the central platform at equal angles. For mice, use shorter (35-cm), narrower (5-cm) arms and a smaller (20-cm) central platform. Each arm has a 5-mm-deep hole 1 cm from the end, which is used as a food cup, and each arm is separated from the center platform by a transparent Plexiglas guillotine door that covers a hole in the Plexiglas wall. The guillotine door can be raised or lowered to allow or prevent entry. The guillotine doors are connected by individual strings to a pulley system that allows the experimenter to open any door from one location within the testing room. Short walls (2 cm high) along the edge of the maze arms prevent the animal from falling off the maze.
    View Image
  •  FigureFigure 11.3.2 Morris water maze. The pool should be watertight, 200 cm in diameter and 75 cm deep, and filled with 50 cm water. The actual dimensions of the pool can be varied depending upon the space available to contain it and whether rats or mice are being tested (e.g., for mice, the pool need only be ~100 cm in diameter and 30 cm deep). The water is made opaque by adding nontoxic white paint or powdered milk. A 10-cm circular escape platform should be constructed of a water-resistant material and covered with material (e.g., cloth) that allows the animal to remain on the top when it is submerged. The platform should be made heavy enough to remain upright when submerged or may be attached to the bottom of the pool. The platform should be 48 to 49 cm in height so that it is submerged 1 to 2 cm below the surface. A chair can be positioned near the pool to allow the experimenter easy access and provide an additional cue for the animal. The water temperature should be maintained at ~20°C. It is useful to have an ample supply of towels nearby to dry animals between trials. Also, an incubator can be used to keep them warm between trials.
    View Image
  •  FigureFigure 11.3.3 The split-stem T maze. For rats, the maze consists of a wooden T-shaped platform with a 87 × 20–cm stem and 40 × 10–cm arms at the end. Black Plexiglas can also be used, and is easier to clean. The entire perimeter of the platform has 5-cm walls to discourage the rat from jumping to the floor. Located 1 cm from the distal end of each arm is a food cup (1 cm wide and 1.5 cm deep). The starting platform is 25 cm long and is separated from the stem by a guillotine door (11 cm high and 6 cm wide), mounted in a frame (22 cm high and 18 cm wide). The stem is divided lengthwise into two halves by a hardware cloth partition (i.e., a taut cloth screen or some other opaque partition, 10 cm high and 20 cm long), that starts 20 cm from the guillotine door. Near the end of the partition proximal to the arms, and extending across both sides of the stem, is a white opaque cloth curtain (14 cm high) suspended in a frame that is perpendicular to the stem. A clear Plexiglas barrier (14 cm high and 8 cm wide, suspended in a frame that is perpendicular to the stem) is placed behind one of the curtains to block access to the arms from that side of the stem. A large cache of food reward is suspended under the ends of the arms, under both food cups to prevent the use of olfactory cues. A rich variety of local and distant cues should surround the maze (e.g., large objects that the animal can see from the maze). These can be removed as required by the particular demands of the experiment. The room should not be too bright, as this tends to frighten the animal. To convert this to a standard T maze (see Basic Protocol 3 and Alternate Protocol 5), the hardware cloth partition, Plexiglas barrier, and curtain can be removed from the stem.
    View Image

Videos

Literature Cited

 Literature Cited
    Aggleton, J.P., Neave, N., Nagle, S., and Hunt, P.R. 1995. A comparison of the effects of anterior thalamic, mammillary body and fornix lesions on reinforced spatial alternation. Behav. Brain Res. 68:91-101.
    Aggleton, J.P., Hunt, P.R., Nagle, S., and Neave, N. 1996. The effects of selective lesions within the anterior thalamic nuclei on spatial memory in the rat. Behav. Brain Res. 81:189-198.
    Avigan, M.R. and Powers, A.S. 1995. The effects of MK-801 injections and dorsal cortex lesions on maze learning in turtles (Chrysemys picta). Psychobiology 23:63-68.
    Barone, S., Stanton, M.E., and Mundy, W.R. 1995. Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with aging. Neurobiol. Aging 16:723-735.
    Becker, J.T., Walker, J.A., and Olton, D.S. 1980. Neuroanatomical bases of spatial memory. Brain Res. 200:307-320.
    Beracochea, D.J. and Jaffard, R. 1995. The effects of mammillary body lesions on delayed matching and delayed non-matching to place tasks in the mice. Behav. Brain Res. 68:45-52.
    Bond, A.B., Cook, R.B., and Lamb, M.R. 1981. Spatial memory and the performance of rats and pigeons in the radial-arm maze. Anim. Learn. & Behav. 9:575-580.
    Brandeis, R., Brandys, Y., and Yehuda, S. 1989. The use of the Morris water maze in the study of memory and learning. Int. J. Neurosci. 48:29-69.
    Brandeis, R., Sapir, M., Kapon, Y., and Borelli, G. 1991. Improvement of cognitive function by MAO-B inhibitor l-deprenyl in aged rats. Pharmacol. Biochem. Behav. 39:297-304.
    Buresova, O. and Skopkova, J. 1982. Vasopressin analogues and spatial working memory in the 24-arm radial maze. Peptides 3:725-727.
    Crawley, J.N., Belknap, J.K., Collins, A., Crabbe, J.C., Frankel, W., Henderson, N., Hitzemann, R.J., Maxson, S.C., Miner, L.L., Silva, A.J., Wehner, J.M., Wynshaw-Boris, A., and Paylor, R. 1997. Behavioral phenotypes of inbred mouse strains: Implications and recommendations for molecular studies. Psychopharmacology 132:107-124.
    Dennis, W. 1939. Spontaneous alternation in rats as an indicator of the persistence of stimulus effects. J. Comp. Psychol. 28:305-312.
    Devenport, L.D., Merriman, V.J., and Devenport, J.A. 1983. Effects of ethanol on enforced spatial variability in the 8-arm radial maze. Pharmacol. Biochem. Behav. 18:55-59.
    Durantou, F., Cazala, P., and Jaffard, R. 1989. Intertrial interval dependent effect of lateral hypothalamic stimulation on spontaneous alternation behavior in a T-maze. Physiol. Behav. 46:253-258.
    Gage, F.H., Dunnett, S.B., and Bjorklund, A. 1984. Spatial learning and motor deficits in aged rats. Neurobiol. Aging 5:43-48.
    Givens, B. and Olton, D.S. 1995. Bidirectional modulation of scopolamine-induced working memory impairments by muscarinic activation of the medial septal area. Neurobiol. Learn. Mem. 63:269-276.
    Hagan, J.J., Alpert, J.E., Morris, R.G., and Iversen, S.D. 1983. The effects of central catecholamine depletions on spatial learning in rats. Behav. Brain Res. 9:83-104.
    Hagan, J.J., Tweedie, F., and Morris, R.G. 1986. Lack of task specificity and absence of posttraining effects of atropine on learning. Behav. Neurosci. 100:483-493.
    Hamilton, G.V. 1911. A study of trial and error reactions in mammals. J. Anim. Behav. 1:33-66.
    Hepler, D., Olton, D., Wenk, G., and Coyle, J. 1985. Lesions of the nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments. J. Neurosci. 5:866-873.
    Hosoi, E., Swift, D.M., Rittenhouse, L.R., and Richards, R.W. 1995. Comparative foraging strategies of sheep and goats in a T-maze apparatus. Appl. Anim. Behav. Sci. 44:37-45.
    Kesner, R.P. and Novak, J.M. 1982. Serial position curve in rats: Role of the dorsal hippocampus. Science 218:173-175.
    Kolb, B., Sutherland, R.J., and Whishaw, I.Q. 1983. A comparison of the contributions of the frontal and parietal association cortex to spatial localization in rats. Behav. Neurosci. 97:13-27.
    Levin, E.D. 1988. Psychopharmacological effects in the radial-arm maze. Neurosci. Biobehav. Rev. 12:169-175.
    Levin, E.D., Wilkerson, A., Jones, J.P., and Christopher, N.C. 1996. Prenatal nicotine effects on memory in rats: Pharmacological and behavioral challenges. Dev. Brain Res. 97:207-215.
    Levy, A., Kluge, P.B., and Elsmore, T.F. 1983. Radial arm maze performance of mice: Acquisition and atropine effects. Behav. Neural Biol. 39:229-240.
    McNamara, R.K. and Skelton, R.W. 1991. Diazepam impairs acquisition but not performance in the Morris water maze. Pharmacol. Biochem. Behav. 38:651-658.
    McNaughton, N. and Morris, R.G. 1987. Chlordiazepoxide, an anxiolytic benzodiazepine, impairs place navigation in rats. Behav. Brain Res. 24:39-46.
    Mendl, M., Erhard, H.W., Haskell, M., and Wemelsfelder, F. 1997. Experience in substrate-enriched and substrate-impoverished environments affects behaviour of pigs in T-maze task. Behavior 134:643-659.
    Morris, R.G.M. 1981. Spatial localisation does not depend on the presence of local cues. Learn. Motiv. 12:239-260.
    Morris, R.G., Garrud, J., Rawlins, N.P., and O'Keefe, J. 1982. Place navigation impaired in rats with hippocampal lesions. Nature 297:681-683.
    Okaichi, J. and Jarrard, L.E. 1982. Scopolamine impairs performance of a place and cue task in rats. Behav. Neural Biol. 35:319-325.
    Olton, D.S. and Samuelson, R.J. 1976. Remembrance of places passed: Spatial memory in rats. Exp. Psychol. [Anim. Behav.] 2:97-116.
    Pitsikas, N., Carli, M., Fidecka, S., and Algeri, S. 1990. Effect of life-long hypocaloric diet on age-related changes in motor and cognitive behavior in a rat population. Neurobiol. Aging 11:417-423.
    Rapp, P.R., Rosenberg, R.A., and Gallagher, M. 1987. An evaluation of spatial information processing in aged rats. Behav. Neurosci. 10:3-12.
    Sanchez-Santed, F., de Bruin, J.P.C., Heinsbroek, R.P.W., and Verwer, R.W.H. 1997. Spatial delayed alternation of rats in a T-maze: Effects of neurotoxic lesions of the medial prefrontal cortex and of T-maze rotations. Behav. Brain Res. 84:73-79.
    Schnurr, R. 1971. Spontaneous alternation in normal and brain-damaged gerbils. Psychol. Sci. 25:181-182.
    Stevens, R. 1981. Scopolamine impairs spatial maze performance in rats. Physiol. & Behav. 27:385-386.
    Sutherland, R.J., Whishaw, I.Q., and Regehr, J.C. 1982. Cholinergic receptor blockade impairs spatial localization by use of distal cues in the rat. J. Comp. Physiol. Psychol. 96:563-573.
    Tolman, E.C. 1925. Purpose and cognition: The determiners of animal learning. Psychol. Rev. 32:285-297.
    Tolman, E.C., Ritchie, F.B., and Kalish, D. 1946. Studies in spatial learning. I. Orientation and the short cut. J. Exp. Psychol. 36:13-24.
    Tsien, J.Z., Huerta, P.T., and Tonegawa, S. 1996. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell. 87:1327-1338.
    Walsh, T.J., Miller, D.B., and Dyer, R.S. 1982. Trimethyltin, a selective limbic system neurotoxicant, impairs radial arm maze performance. Neurobehav. Toxicol. Teratol. 4:177-183.
    Watts, J., Stevens, R., and Clare, R. 1981. Effects of scopolamine on radial maze performance, male rats, implications for hippocampal role in spatial memory. Physiol. & Behav. 26:845-851.
    Wenk, G.L., Hughey, D., Boundy, V., Kim, A., Walker, L., and Olton, D.S. 1987. Neurotransmitters and memory: The role of cholinergic, serotonergic and noradrenergic systems. Behav. Neurosci. 101:325-332.
    Wenk, G.L., Markowska, A.L., and Olton, D.S. 1989. Basal forebrain lesions and memory: Alterations in neurotensin, not acetylcholine, may cause amnesia. Behav. Neurosci. 103:765-769.
    Wenk, G., Sweeney, J., Hughey, D., Carson, J., and Olton, D. 1986. Choline acetyltransferase inhibition does not impair radial maze performance in rats. Pharmacol. Biochem. Behav. 25:521-526.
    White, S.R. 1974. Atropine, scopolamine and hippocampal lesion effects on alternation performance of rats. Pharmacol. Biochem. Behav. 2:297-307.
 Key References
    Brandeis et al. 1989 See 1989.

Provides a general review of the many ways the water maze task has been used to study brain function and the general theoretical principles that underlie its use.

    Hepler, et al. 1985 See 1985.

Provides an introduction to the use of the split-stem T maze to determine the effects of specific brain lesions.

    Olton, D.S. 1983. The use of animal models to evaluate the effects of neurotoxins on cognitive processes. Neurobehav. Toxicol. Teratol. 5:635-640.

This review describes the use of many different behavioral tasks in toxicological studies.

    Olton, D.S. 1985. The radial arm maze as a tool in behavioral pharmacology. Physiol. & Behav. 40:793-797.

Reviews the many ways in which the radial arm maze task has been and can be used to investigate the effects of lesions or drugs upon the function of specific brain regions.

    Richman, C.L., Dember, W.N., and Kim, P. 1986/1987 Spontaneous alternation behavior in animals: A review. Curr. Psychol. Res. Rev. 5:358-391.

Provides a general review of the use of the standard T maze to study spontaneous alternation behavior.

    Stanton, M.E. 1992. Animal models of cognitive development in neurotoxicology. In The Vulnerable Brain and Environmental Risks, Vol. 1: Malnutrition and Hazard Assessment (R.L. Isaacson and K.F. Jenson, eds.) pp. 129-146. Plenum Press, New York.

This review describes the use of many different behavioral tasks in toxicological studies.

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