Water Maze Testing to Identify Compounds for Cognitive Enhancement

Gregory M. Rose1, Wayne B. Rowe2

1 Center for Integrated Research in Cognitive & Neural Sciences and Departments of Anatomy and Physiology, Southern Illinois University, Carbondale, Illinois, 2 External Innovations, Sanofi, Bridgewater, New Jersey
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.63
DOI:  10.1002/0471141755.ph0563s59
Online Posting Date:  December, 2012
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

The water maze task is widely used to evaluate spatial learning and memory in rodents. The basic paradigm requires an animal to swim in a pool until it finds a hidden escape platform. The animals learn to find the platform using extra‐maze cues and, after several training trials, are able to swim directly to it from any starting location. Memory for the platform location is assessed by examining swimming behavior with the platform removed from the maze, while sensory, motor and motivational aspects of the task can be examined by making the platform visible to the animals. Described in this unit is the use of the water maze to identify rats with age‐related spatial learning and memory impairments. The efficacy of potential pharmacological treatments for alleviating these deficits is then evaluated. This assay provides a means for studying the neurobiology of spatial learning and memory, and to identify potential pharmacotherapies for treating memory‐impaired humans. While the use of aged rats is described in this unit, the protocol can also be employed for compound screening with other rodent models that have spatial learning and memory impairments, such as transgenic mouse models of Alzheimer's disease. Curr. Protoc. Pharmacol. 59:5.63.1‐5.63.12. © 2012 by John Wiley & Sons, Inc.

Keywords: water maze; spatial memory; aging; cognition rodent

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Strategic Planning
  • Basic Protocol 1: Testing Cognition Enhancers Using Aged Rats in the Water Maze
  • Commentary
  • Literature Cited
  • Figures
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Testing Cognition Enhancers Using Aged Rats in the Water Maze

  Materials
  • Male Fischer 344 Rats, 3 to 6 months and 23 to 24 months old (Hilltop Lab Animals)
  • Test compounds
  • Reference compounds (e.g., donepezil, memantine, GTS‐21, SB 271046 from Sigma‐Aldrich)
  • Vehicle solution used for test and/or reference compounds
  • Water maze apparatus (see Strategic Planning)
  • Stopwatch or computerized tracking system [e.g., Water 2100, sold by HVS Image (http://www.hvsimage.com) or ANY‐maze sold by San Diego Instruments (http://www.sandiegoinstruments.com) and Stoelting (http://www.stoelting.com)]
  • Home cages
  • Large scoop or similar object (e.g., flat kitchen sieve with a handle)
NOTE: Other rat strains, such as Long‐Evans, could also be used. Aged Sprague‐Dawley rats develop vision impairments, so they should be avoided. C57BL6 mice are available from many breeders and also show age‐related spatial learning impairments.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Antonova, E., Parslow, D., Brammer, M., Dawson, G.R., Jackson, S.H., and Morris, R.G. 2009. Age‐related neural activity during allocentric spatial memory. Memory 17:125‐143.
   Astur, R.S., Taylor, L.B., Mamelak, A.N., Philpott, L., and Sutherland, R.J. 2002. Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task. Behav. Brain Res. 132:77‐84.
   Barten, D.M., Fanara, P., Andorfer, C., Hoque, N., Wong, P.Y., Husted, K.H., Cadelina, G.W., Decarr, L.B., Yang, L., Liu, V., Fessler, C., Protassio, J., Riff, T., Turner, H., Janus, C.G., Sankaranarayanan, S., Polson, C., Meredith, J.E., Gray, G., Hanna, A., Olson, R.E., Kim, S.H., Vite, G.D., Lee, F.Y., and Albright, C.F. 2012. Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau transgenic mice with low doses of the microtubule‐stabilizing agent BMS‐241027. J. Neurosci. 32:7137‐7145.
   Buresová, O., Krekule, I., Zahálka, A., and Bures, J. 1985. On‐demand platform improves accuracy of the Morris water maze procedure. J. Neurosci. Meth. 15:63‐72.
   Colombo, P.J. and Gallagher, M. 2002. Individual differences in spatial memory among aged rats are related to hippocampal PKCgamma immunoreactivity. Hippocampus 12:285‐289.
   Gallagher, M., Burwell, R.D., and Burchinal, M. 1993. Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. Behav. Neurosci. 107:618‐626.
   Hersi, A.I., Rowe, W., Gaudreau, P., and Quirion, R. 1995. Dopamine D1 receptor ligands modulate cognitive performance and hippocampal acetylcholine release in memory‐impaired aged rats. Neuroscience 69:1067‐1074.
   Maei, H.R., Zaslavsky, K., Teixeira, C.M., and Frankland, P.W. 2009. What is the most sensitive measure of water maze probe test performance? Front. Integr. Neurosci. 3:4.
   Markowska, A.L., Koliatsos, V.E., Breckler, S.J., Price, D.L., and Olton, D.S. 1994. Human nerve growth factor improves spatial memory in aged but not in young rats. J. Neurosci. 14:4815‐4824.
   Millan, M.J., Agid, Y., Brüne, M., Bullmore, E.T., Carter, C.S., Clayton, N.S., Connor, R., Davis, S., Deakin, B., DeRubeis, R.J., Dubois, B., Geyer, M.A., Goodwin, G.M., Gorwood, P., Jay, T.M., Joëls, M., Mansuy, I.M., Meyer‐Lindenberg, A., Murphy, D., Rolls, E., Saletu, B., Spedding, M., Sweeney, J., Whittington, M., and Young, L.J. 2012. Cognitive dysfunction in psychiatric disorders: Characteristics, causes and the quest for improved therapy. Nat. Rev. Drug Discov. 11:141‐168.
   Morgan, D., Diamond, D.M., Gottschall, P.E., Ugen, K.E., Dickey, C., Hardy, J., Duff, K., Jantzen, P., DiCarlo, G., Wilcock, D., Connor, K., Hatcher, J., Hope, C., Gordon, M., and Arendash, G.W. 2000. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408:982‐985.
   Morris, R.G.M. 1981. Spatial localization does not require the presence of local cues. Learn. Motiv. 12:239‐260.
   Morris, R. 1984. Developments of a water‐maze procedure for studying spatial learning in the rat. J. Neurosci. Meth. 11:47‐60.
   Ohta, H., Arai, S., Akita, K., Ohta, T., and Fukuda, S. 2012. Effects of NK‐4 in a transgenic mouse model of Alzheimer's disease. PLoS One 7:e30007.
   Owen, E.H., Logue, S.F., Rasmussen, D.L., and Wehner, J.M. 1997. Assessment of learning by the Morris water task and fear conditioning in inbred mouse strains and F1 hybrids: Implications of genetic background for single gene mutations and quantitative trait loci analyses. Neuroscience 80:1087‐1099.
   Rowe, W.B., Blalock, E.M., Chen, K.C., Kadish, I., Wang, D., Barrett, J.E., Thibault, O., Porter, N.M., Rose, G.M., and Landfield, P.W. 2007. Hippocampal expression analyses reveal selective association of immediate‐early, neuroenergetic, and myelinogenic pathways with cognitive impairment in aged rats. J. Neurosci. 27:3098‐3110.
   Schoenfeld, R., Moenich, N., Mueller, F.J., Lehmann, W., and Leplow, B. 2010. Search strategies in a human water maze analogue analyzed with automatic classification methods. Behav. Brain Res. 208:169‐177.
   Spencer, R.L., O'Steen, W.K., and McEwen, B.S. 1995. Water maze performance of aged Sprague‐Dawley rats in relation to retinal morphologic measures. Behav. Brain Res. 68:139‐150.
   Spooner, R.I., Thomson, A., Hall, J., Morris, R.G., and Salter, S.H. 1994. The Atlantis platform: A new design and further developments of Buresova's on‐demand platform for the water maze. Learn. Mem. 1:203‐211.
   Tombaugh, G.C., Rowe, W.B., Chow, A.R., Michael, T.H., and Rose, G.M. 2002. Theta‐frequency synaptic potentiation in CA1 in vitro distinguishes cognitively impaired from unimpaired aged Fischer 344 rats. J. Neurosci. 22:9932‐9940.
   Veng, L.M., Granholm, A.C., and Rose, G.M. 2003. Age‐related sex differences in spatial learning and basal forebrain cholinergic neurons in F344 rats. Physiol. Behav. 80:27‐36.
   Vorhees, C.V. and Williams, M.T. 2006. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protoc. 1:848‐858.
   Wallace, T.L., Callahan, P.M., Tehim, A., Bertrand, D., Tombaugh, G., Wang, S., Xie, W., Rowe, W.B., Ong, V., Graham, E., Terry, A.V. Jr., Rodefer, J.S., Herbert, B., Murray, M., Porter, R., Santarelli, L., and Lowe, D.A. 2011. RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents. J. Pharmacol. Exp. Ther. 336:242‐253.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library