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Morris water maze: procedures for assessing spatial and related forms of learning and memory

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Vorhees, Charles V, Williams, Michael T·2006·Nature Protocols

Abstract

The Morris water maze (MWM) is a test of spatial learning for rodents that relies on distal cues to navigate from start locations around the perimeter of an open swimming arena to locate a submerged escape platform. Spatial learning is assessed across repeated trials and reference memory is determined by preference for the platform area when the platform is absent. Reversal and shift trials enhance the detection of spatial impairments. Trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol. Search-to-platform area determines the degree of reliance on spatial versus non-spatial strategies. Cued trials determine whether performance factors that are unrelated to place learning are present. Escape from water is relatively immune from activity or body mass differences, making it ideal for many experimental models. The MWM has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function. We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days.

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  • Spatial navigation paradigms are known to depend on normal synaptic function in the hippocampal CA1 region.

    “spatial navigation paradigms, which are known to be dependent on normal synaptic function in this region (Kleinknecht et al. 2012; Vorhees and Williams 2006).”

    From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Vorhees and Williams 2006

    The Introduction (page unavailable) links Morris water maze performance to long-term potentiation and NMDA receptor function and describes the task as useful for investigating hippocampal circuitry. It does not establish that spatial navigation paradigms depend on normal synaptic function specifically in hippocampal CA1; a search for CA1 found no such passage. (LLM, conf=0.85)

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  1. [1]Morris RGM. Spatial localization does not require the presence of local cues. Learn Motiv. 1981;12:239–260. [Google Scholar]
  2. [2]Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11:47–60. doi: 10.1016/0165-0270(84)90007-4. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  3. [3]Stewart CA, Morris RGM. The watermaze. In: Sahgal A, editor. Behavioural Neuroscience, Volume I, A Practical Approach. IRL Press at Oxford University Press; Oxford: 1993. pp. 107–122. [Google Scholar]
  4. [4]Kallai J, Makany T, Karadi K, Jacobs WJ. Spatial orientation strategies in Morris-type virtual water task for humans. Behav Brain Res. 2005;159:187–196. doi: 10.1016/j.bbr.2004.10.015. [DOI] [PubMed] [Google Scholar] · DOI
  5. [5]Morris RGM. An attempt to dissociate ‘spatial-mapping’ and ‘working-memory’ theories of hippocampal function. In: Seifert W, editor. Neurobiology of the Hippocampus. Academic Press; New York: 1993. pp. 405–432. [Google Scholar]
  6. [6]Cravens RW. Effects of maternal undernutrition on offspring behavior: Incentive value of a food reward and ability to escape from water. Dev Psychobiol. 1974;7:61–69. doi: 10.1002/dev.420070110. [DOI] [PubMed] [Google Scholar] · DOI
  7. [7]Morris RG, Garrud P, Rawlins JN, O’Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature. 1982;297:681–683. doi: 10.1038/297681a0. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  8. [8]Fitzgerald LW, Dokla CP. Morris water task impairment and hypoactivity following cysteamine-induced reductions of somatostatin-like immunoreactivity. Brain Res. 1989;505:246–250. doi: 10.1016/0006-8993(89)91450-9. [DOI] [PubMed] [Google Scholar] · DOI
  9. [9]Brandeis R, Brandys Y, Yehuda S. The use of the Morris water maze in the study of memory and learning. Int J Neurosci. 1989;48:29–69. doi: 10.3109/00207458909002151. [DOI] [PubMed] [Google Scholar] · DOI
  10. [10]D’Hooge R, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Rev. 2001;36:60–90. doi: 10.1016/s0165-0173(01)00067-4. [DOI] [PubMed] [Google Scholar] · DOI
  11. [11]McNamara RK, Skelton RW. The neuropharmacological and neurochemical basis of place learning in the Morris water maze. Brain Res Rev. 1993;18:33–49. doi: 10.1016/0165-0173(93)90006-l. [DOI] [PubMed] [Google Scholar] · DOI
  12. [12]Jeffery KJ, Morris RGM. Cumulative long-term potentiation in the rat dentate gyrus correlates with, but does not modify, performance in the water maze. Hippocampus. 1993;3:133–140. doi: 10.1002/hipo.450030205. [DOI] [PubMed] [Google Scholar] · DOI
  13. [14]Morris RGM, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate antagonist, AP5. Nature. 1986;329:774–776. doi: 10.1038/319774a0. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  14. [15]Bannerman DM, Good MA, Butcher SP, Ramsay M, Morris RGM. Distinct components of spatial learning revealed by prior training and NMDA receptor blockade. Nature. 1995;378:182–186. doi: 10.1038/378182a0. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  15. [16]Vorhees CV, et al. Adult learning deficits after neonatal exposure to D-methamphetamine: Selective effects on spatial navigation and memory. J Neurosci. 2000;20:4732–4739. doi: 10.1523/JNEUROSCI.20-12-04732.2000. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  16. [17]Broening HW, Morford LL, Inman-Wood SL, Fukumura M, Vorhees CV. 3,4-methylenedioxymethamphetamine (ecstasy) induced learning and memory impairments depend on the age of exposure during early development. J Neurosci. 2001;21:3228–3235. doi: 10.1523/JNEUROSCI.21-09-03228.2001. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  17. [18]Vorhees CV, Reed TM, Skelton MR, Williams MT. Exposure to 3,4- methylenedioxymethamphetamine (MDMA) on postnatal days 11–20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning. Int J Dev Neurosci. 2004;22:247–259. doi: 10.1016/j.ijdevneu.2004.06.003. [DOI] [PubMed] [Google Scholar] · DOI
  18. [19]Williams MT, et al. Developmental d-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory. Synapse. 2003;48:138–148. doi: 10.1002/syn.10159. [DOI] [PubMed] [Google Scholar] · DOI
  19. [20]Morford LL, Inman-Wood SL, Gudelsky GA, Williams MT, Vorhees CV. Impaired spatial and sequential learning in rats treated neonatally with d-fenfluramine. Eur J Neurosci. 2002;16:491–500. doi: 10.1046/j.1460-9568.2002.02100.x. [DOI] [PubMed] [Google Scholar] · DOI
  20. [22]Silva AJ, Paylor R, Wehner JM, Tonegawa S. Impaired spatial learning in α-calcium-calmodulin kinase II mutant mice. Science. 1992;257:206–211. doi: 10.1126/science.1321493. [DOI] [PubMed] [Google Scholar] · DOI
  21. [23]Bourtchuladze R, et al. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell. 1994;79:59–68. doi: 10.1016/0092-8674(94)90400-6. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  22. [25]Upchurch M, Wehner JM. Effects of N-methyl-D-aspartate antagonism on spatial learning in mice. Psychopharmacology. 1990;100:214. doi: 10.1007/BF02244408. [DOI] [PubMed] [Google Scholar] · DOI
  23. [26]Grant SGN, et al. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. Science. 1992;258:1903–1910. doi: 10.1126/science.1361685. [DOI] [PubMed] [Google Scholar] · DOI
  24. [27]Limback-Stokin K, Korzus E, Nagaoka-Yasuda R, Mayford M. Nuclear calcium/calmodulin regulates memory consolidation. J Neurosci. 2004;24:10858–10867. doi: 10.1523/JNEUROSCI.1022-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  25. [28]Tang YP, et al. Genetic enhancement of learning and memory in mice. Nature. 1999;401:63–69. doi: 10.1038/43432. [DOI] [PubMed] [Google Scholar] · DOI
  26. [29]Maurer R, Derivaz V. Rats in a transparent morris water maze use elemental and configural geometry of landmarks as well as distance to the pool wall. Spatial Cogn Comput. 2000;2:135–156. [Google Scholar]
  27. [30]Kim JJ, Lee HJ, Han JS, Packard MG. Amygdala is critical for stress-induced modulation of hippocampal long-term potentiation and learning. J Neurosci. 2001;21:5222–5228. doi: 10.1523/JNEUROSCI.21-14-05222.2001. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  28. [31]Markowska AL, Long JM, Johnson CT, Olton DS. Variable-interval probe test as a tool for repeated measurements of spatial memory in the water maze. Behav Neurosci. 1993;107:627–632. doi: 10.1037//0735-7044.107.4.627. [DOI] [PubMed] [Google Scholar] · DOI
  29. [32]Sutherland RJ, Chew GL, Baker JC, Linggard RC. Some limitations on the use of distal cues in place navigation by rats. Psychobiology. 1987;15:48–57. [Google Scholar]
  30. [33]Williams MT, et al. Developmental 3,4-methylenedioxymethamphetamine (MDMA) impairs sequential and spatial but not cued learning independent of growth, litter effects, or injection stress. Brain Res. 2003;968:89–101. doi: 10.1016/s0006-8993(02)04278-6. [DOI] [PubMed] [Google Scholar] · DOI
  31. [34]Saucier D, Cain DP. Spatial learning without NMDA receptor-dependent long-term potentiation. Nature. 1995;378:186–189. doi: 10.1038/378186a0. [DOI] [PubMed] [Google Scholar] · DOI
  32. [35]Saucier D, Hargreaves EL, Boon F, Vanderwolf CH, Cain DP. Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: Nonspatial pretraining eliminates spatial learning deficits. Behav Neurosci. 1996;110:103–116. [PubMed] [Google Scholar]
  33. [36]Cain DP, Saucier D, Hall J, Hargreaves EL, Boon F. Detailed behavioral analysis of water maze acquisition under APV or CNQX: Contribution of sensorimotor disturbances to drug-induced acquisition deficits. Behav Neurosci. 1996;110:86–102. doi: 10.1037//0735-7044.110.1.86. [DOI] [PubMed] [Google Scholar] · DOI
  34. [37]Cain DP, Saucier D. The neuroscience of spatial navigation: Focus on behavior yields advances. Rev Neurosci. 1996;7:215–231. doi: 10.1515/revneuro.1996.7.3.215. [DOI] [PubMed] [Google Scholar] · DOI
  35. [38]Hoh TE, Cain DP. Fractionating the nonspatial pretraining effect in the water maze task. Behav Neurosci. 1997;111:1285–1291. doi: 10.1037//0735-7044.111.6.1285. [DOI] [PubMed] [Google Scholar] · DOI
  36. [39]Williams MT, Vorhees CV, Boon F, Saber AJ, Cain DP. Methamphetamine exposure from postnatal days 11 to 20 causes impairments in both behavioral strategies and spatial learning in adult rats. Brain Res. 2002;958:312–321. doi: 10.1016/s0006-8993(02)03620-x. [DOI] [PubMed] [Google Scholar] · DOI
  37. [40]Whishaw IQ. Posterior neocortical (visual cortex) lesions in the rat impair matching-to-place navigation in a swimming pool: a reevaluation of cortical contributions to spatial behavior using a new assessment of spatial versus non-spatial behavior. Behav Brain Res. 2004;155:177–184. doi: 10.1016/j.bbr.2004.04.013. [DOI] [PubMed] [Google Scholar] · DOI
  38. [41]Blokland A, Geraerts E, Been M. A detailed analysis of rats’ spatial memory in a probe trial of a Morris task. Behav Brain Res. 2004;154:71–75. doi: 10.1016/j.bbr.2004.01.022. [DOI] [PubMed] [Google Scholar] · DOI
  39. [42]Morris RGM, Hagan JJ, Rawlins JNP. Allocentric spatial learning by hippocampectomized rats: A further test of the ‘spatial mapping’ and ‘working memory’ theories of hippocampal function. Quart J Exp Psychol. 1986;38B:365–395. [PubMed] [Google Scholar]
  40. [43]Morris RGM, Davis S, Butcher SP. Hippocampal synaptic plasticity and NMDA receptors: A role in information storage? Phil Trans R Soc Lond. 1990;329:187–204. doi: 10.1098/rstb.1990.0164. [DOI] [PubMed] [Google Scholar] · DOI
  41. [44]Upchurch M, Wehner JM. Differences between inbred strains of mice in Morris water maze performance. Behav Genet. 1988;18:55–68. doi: 10.1007/BF01067075. [DOI] [PubMed] [Google Scholar] · DOI
  42. [45]Wahlsten D, Cooper SF, Crabbe JC. Different rankings of inbred mouse strains on the Morris maze and a refined 4-arm water escape task. Behav Brain Res. 2005;165:36–51. doi: 10.1016/j.bbr.2005.06.047. [DOI] [PubMed] [Google Scholar] · DOI
  43. [46]Wenk GL. In: Assessment of spatial memory using the radial arm and Morris water maze. Unit 8.5A. Crawley JN, et al., editors. Wiley Interscience; New York: 2004. [DOI] [PubMed] [Google Scholar]
  44. [47]Williams MT, Moran MS, Vorhees CV. Behavioral and growth effects induced by low dose methamphetamine administration during the neonatal period in rats. Int J Dev Neurosci. 2004;22:273–283. doi: 10.1016/j.ijdevneu.2004.04.003. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  45. [48]Mactutus CF, Booze RM. Accuracy of spatial navigation: The role of platform and tank size. Soc Neurosci Abst. 1994;20:1014. [Google Scholar]
  46. [49]Lindner MD, Ribkoff VK. Relationship between performance in the Morris water task, visual acuity, and thermoregulatory function in aged F-344 rats. Behav Brain Res. 1991;45:45–55. doi: 10.1016/s0166-4328(05)80179-2. [DOI] [PubMed] [Google Scholar] · DOI
  47. [50]Hodges H. Maze procedures: The radial-arm and water maze compared. Cog Brain Res. 1996;3:167–181. doi: 10.1016/0926-6410(96)00004-3. [DOI] [PubMed] [Google Scholar] · DOI
  48. [51]Iivonen H, Nurminen L, Harri M, Tanila H, Puolivali J. Hypothermia in mice tested in Morris water maze. Behav Brain Res. 2003;141:207–213. doi: 10.1016/s0166-4328(02)00369-8. [DOI] [PubMed] [Google Scholar] · DOI
  49. [52]Devan BD, Blank GS, Petri HL. Place navigation in the Morris water task: Effects of reducted platform interval lighting and pseudorandom plaform positioning. Psychobiology. 1992;20:120–126. [Google Scholar]
  50. [53]Otnaess MK, Brun VH, Moser MB, Moser EI. Pretraining prevents spatial learning impairment after saturation of hippocampal long-term potentiation. J Neurosci. 1999;19 (RC49):1–5. doi: 10.1523/JNEUROSCI.19-24-j0007.1999. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  51. [54]Gallagher M, Burwell R, Burchinal M. Severity of spatial learning impairment in aging: Development of a learning index for performance in the Morris water maze. Behav Neurosci. 1993;107:618–626. doi: 10.1037//0735-7044.107.4.618. [DOI] [PubMed] [Google Scholar] · DOI
  52. [55]Burwell RD, Saddoris MP, Bucci DJ, Wiig KA. Corticohippocampal contributions to spatial and contextual learning. J Neurosci. 2004;24:3826–3836. doi: 10.1523/JNEUROSCI.0410-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  53. [56]Holscher C. Stress impairs performance in spatial watermaze learning tasks. Behav Brain Res. 1999;100:225–235. doi: 10.1016/s0166-4328(98)00134-x. [DOI] [PubMed] [Google Scholar] · DOI
  54. [57]Clapcote SJ, Lazar NL, Bechard AR, Wood GA, Roder JC. NIH Swiss and Black Swiss mice have retinal degeneration and performance deficits in cognitive tests. Comp Med. 2005;55:310–316. [PubMed] [Google Scholar]
  55. [58]Devan BD, McDonald RJ, White NM. Effects of medial and lateral caudate-putamen lesions on place- and cue-guided behaviors in the water maze: relation to thigmotaxis. Behav Brain Res. 1999;100:5–14. doi: 10.1016/s0166-4328(98)00107-7. [DOI] [PubMed] [Google Scholar] · DOI
  56. [59]Rauch TM, Welch DI, Gallego L. Hyperthermia impairs retrieval of an overtrained spatial task in the Morris water maze. Behav Neural Biol. 1989;52:321–330. doi: 10.1016/s0163-1047(89)90442-1. [DOI] [PubMed] [Google Scholar] · DOI
  57. [60]Giese KP, Fedorov NB, Filipkowski RK, Silva AJ. Autophosphorylation at Thr286 of the α calcium-calmodulin kinase II in LTP and learning. Science. 1998;279:870–873. doi: 10.1126/science.279.5352.870. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  58. [61]Guzowski JF, Setlow B, Wagner EK, McGaugh JL. Experience-dependent gene expression in the rat hippocampus after spatial learning: A comparison of the immediate-early genes Arc, c-fos, and zif268. J Neurosci. 2001;21:5089–5098. doi: 10.1523/JNEUROSCI.21-14-05089.2001. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  59. [62]Brown RW, et al. Adulthood nicotine treatment alleviates behavioural impairments in rats neonatally treated with quinpirole: possible roles of acetylcholine function and neurotrophic factor expression. Eur J Neurosci. 2004;19:1634–1642. doi: 10.1111/j.1460-9568.2004.03199.x. [DOI] [PubMed] [Google Scholar] · DOI
  60. [63]Wolfer DP, Stagljar-Bozicevic M, Errington ML, Lipp HP. Spatial memory and learning in transgenic mice: Fact or artifact? News Physiol Sci. 1998;13:118–123. doi: 10.1152/physiologyonline.1998.13.3.118. [DOI] [PubMed] [Google Scholar] · DOI
  61. [64]Lipp HP, Wolfer DP. Genetically modified mice and cognition. Curr Opin Neurobiol. 1998;8:272–280. doi: 10.1016/s0959-4388(98)80151-7. [DOI] [PubMed] [Google Scholar] · DOI

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Sorted by citations

Authors
Vorhees, C. V., & Williams, M. T.
Affiliations
Cincinnati Children's Hospital Medical Center (US)
Corresponding author
Vorhees, Charles V
Venue
Nature Protocols
Published
2006-07-27
Volume
1
Issue
2
Pages
848-858
ISSN
  • 1750-2799 (ISSN-L)
  • 1754-2189
OpenAlex
W1994580609
Cited by
4,629
References
3
Citations by year
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FWCI
11.34
Type
journal article
Language
en
Open access
Locations
  • Nature Protocols (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Drug Abuse (R01DA021394, DA014269, K01DA014269, DA 006733, R01DA006733, DA021394)
  • National Institute of Environmental Health Sciences (T32ES007051, ES007051)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Physical Sciences › Engineering › Automotive Engineering › Spatial Cognition and Navigation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Morris water maze, spatial learning, spatial memory, reference memory, reversal learning, latent learning, discrimination learning, hippocampal synaptic plasticity
MeSH terms
Animals, Cues, Memory, Psychomotor Performance, Spatial Behavior, Swimming, Water, Maze Learning, Mice, Rats

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