Advertisement

Behavioral Methods to Study Learning and Memory in Rats

  • Jorge Alberto QuillfeldtEmail author

Abstract

This century-old observation is still valid today, despite everything we have learned about the mammal nervous system, especially in the area of neurobiology of learning and memory. After “training” an experimental animal, such as a rat or a mouse, the only way to be sure that a “memory” was formed is by evoking it back, i.e., by recalling it in a “test” session: this “memory” is expressed by a behavior that differs from that one emitted in the training session. Until proof to the contrary, the best explanation for this new response to the same context is that some kind of internal modification—a “record”—mediates it inside the animal: this is what we call “memory”. Everything else is consequence: if recalling depends upon the established memory trace intensity, it will be a function of the experience intensity during the acquisition, or “training”, session, and so on.

Keywords

Conditioned Stimulus Test Session Unconditioned Stimulus Escape Latency Behavioral Task 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Science involves a long apprenticeship and, at last, always remains a collective endeavor. Anyway, some people deserve to be mentioned with special care: I would like to thank my former tutor, Dr. Ivan Izquierdo (PUCRS, Brazil), for the privilege of his friendship. I would also like to acknowledge Dr. James McGaugh (UCI, USA) for all the precious lessons over the years. Finally, I would like to thank my good friends Dr. Diana Jerusalinsky (UBA, Argentina) and Victor Molina (UNC, Argentina). I also thank each one of them for kindly reading this manuscript, but I, alone, am responsible for any errors found here.

References

  1. Anisman H. Aversively motivated behavior as a tool in psychopharmacologic analysis. In: Anisman H, Bignami G, editors. Psychopharmacology of aversively motivated behavior. New York: Plenum Press; 1978. p. 1–62.CrossRefGoogle Scholar
  2. Anisman H, Bignami G. Psychopharmacology of aversively motivated behavior. New York: Plenum Press; 1978.CrossRefGoogle Scholar
  3. Bannerman DM, Chapman PF, Kelly PA, Butcher SP, Morris RG. Inhibition of nitric oxide synthase does not impair spatial learning. J Neurosci. 1994;14:7404–14.PubMedGoogle Scholar
  4. Barros DM, Pereira P, Medina JH, Izquierdo I. Modulation of working memory and of long- but not short-term memory by cholinergic mechanisms in the basolateral amygdala. Behav Pharmacol. 2002;13:163–7.CrossRefPubMedGoogle Scholar
  5. Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH. BDNF is essential to promote persistence of long-term memory storage. Proc Natl Acad Sci U S A. 2008;105:2711–6.PubMedCentralCrossRefPubMedGoogle Scholar
  6. Beninger RJ. Methods for determining the effects of drugs on learning. In: Boulton AB, Baker GB, Greenshaw AJ, editors. Neuromethods. Psychopharmacology. Clifton: Humana Press; 1989. p. 623–85.CrossRefGoogle Scholar
  7. Bermudez-Rattoni F, Introini-Collison I, Coleman-Mesches K, McGaugh JL. Insular cortex and amygdala lesions induced after aversive training impair retention: effects of degree of training. Neurobiol Learn Mem. 1997;67:57–63.CrossRefPubMedGoogle Scholar
  8. Blanchard RJ, Blanchard DC. Crouching as an index of fear. J Comp Physiol Psychol. 1969;67:370–5.CrossRefPubMedGoogle Scholar
  9. Blanchard RJ, Blanchard DC. Dual mechanisms in passive avoidance I & II. Psychon Sci. 1970;19:1–4.CrossRefGoogle Scholar
  10. Blanchard RJ, Blanchard DC, Fial RA. Hippocampal lesions in rats and their effect on activity, avoidance, and aggression. J Comp Physiol Psychol. 1970;71:92–101.CrossRefPubMedGoogle Scholar
  11. Boccia MM, Acosta GB, Blake MG, Baratti CM. Memory consolidation and reconsolidation of an inhibitory avoidance response in mice: effects of i.c.v. injections of hemicholinium-3. Neuroscience. 2004;124:735–41.CrossRefPubMedGoogle Scholar
  12. Bolles RC, Collier AC. Effect of predictive cues on freezing in rats. Anim Learn Behav. 1976;4:6–8.CrossRefGoogle Scholar
  13. Boulton AB, Baker GB, Greenshaw AJ. Neuromethods. Psychopharmacology. Clifton: Humana Press; 1989.CrossRefGoogle Scholar
  14. Bouton ME, Westbrook FR, Corcoran KA, Maren S. Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry. 2006;60:352–60.CrossRefPubMedGoogle Scholar
  15. Brillaud E, Morillion D, de Seze R. Modest environmental enrichment: effect on a radial maze validation and well being of rats. Brain Res. 2005;1054:174–82.CrossRefPubMedGoogle Scholar
  16. Bustos SG, Maldonado H, Molina VA. Midazolam disrupts fear memory reconsolidation. Neuroscience. 2006;139:831–42.CrossRefPubMedGoogle Scholar
  17. Bustos SG, Maldonado H, Molina VA. The disruptive effect of midazolam on fear memory reconsolidation: decisive influence of reactivation time span and memory age. Neuropsychopharmacology. 2009;34:446–57.CrossRefPubMedGoogle Scholar
  18. Callegari-Jacques SM. Bioestatística—princípios e aplicações. Porto Alegre, Brasil: Artmed; 2003.Google Scholar
  19. Cammarota M, Bevilaqua LR, Kerr D, Medina JH, Izquierdo I. Inhibition of mRNA and protein synthesis in the CA1 region of the dorsal hippocampus blocks reinstallment of an extinguished conditioned fear response. J Neurosci. 2003;23:737–41.PubMedGoogle Scholar
  20. Carobrez AP, Bertoglio LJ. Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on. Neurosci Biobehav Rev. 2005;29:1193–205.CrossRefPubMedGoogle Scholar
  21. Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, Turski L. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia. 1991;32:778–82.CrossRefPubMedGoogle Scholar
  22. Debiec J, LeDoux JE. Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Neuroscience. 2004;129:267–72.CrossRefPubMedGoogle Scholar
  23. Debiec J, LeDoux JE, Nader K. Cellular and systems reconsolidation in the hippocampus. Neuron. 2002;36:527–38.CrossRefPubMedGoogle Scholar
  24. Dudai Y. The neurobiology of consolidations, or, how stable is the engram? Annu Rev Psychol. 2000;55:51–86.CrossRefGoogle Scholar
  25. Duvarci S, Nader K. Characterization of fear memory reconsolidation. J Neurosci. 2004;24:9269–75.CrossRefPubMedGoogle Scholar
  26. Eisenberg M, Kobilo T, Berman DE, Dudai Y. Stability of retrieved memory: inverse correlation with trace dominance. Science. 2003;301:1102–4.CrossRefPubMedGoogle Scholar
  27. File SE, Gonzalez LE, Gallant R. Role of the basolateral nucleus of the amygdala in the formation of a phobia. Neuropsychopharmacology. 1998;19:397–405.CrossRefPubMedGoogle Scholar
  28. Flecknell P. Laboratory animal anesthesia. 2nd ed. London: Academic; 1996.Google Scholar
  29. Frenkel L, Maldonado H, Delorenzi A. Memory strengthening by a real-life episode during reconsolidation: an outcome of water deprivation via brain angiotensin II. Eur J Neurosci. 2005;22:1757–66.CrossRefPubMedGoogle Scholar
  30. Gold PE. The use of avoidance training in studies of modulation of memory storage. Behav Neural Biol. 1986;46:87–98.CrossRefPubMedGoogle Scholar
  31. Hölscher C, O’Mara SM. Model learning and memory systems in neurobiological research: conditioning and associative learning procedures and spatial learning paradigms. In: Lynch MA, O’Mara SM, editors. Neuroscience Labfax. London: Academic; 1997.Google Scholar
  32. Hughes RN. The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neurosci Biobehav Rev. 2004;28:497–505.CrossRefPubMedGoogle Scholar
  33. Izquierdo I. Different forms of post-training memory processing. Behav Neural Biol. 1989;51:171–202.CrossRefPubMedGoogle Scholar
  34. Izquierdo I. Memória. Porto Alegre: Artmed; 2002.Google Scholar
  35. Izquierdo I, Dias RD. Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphin with ACTH or epinephrine on memory consolidation. Psychoneuroendocrinology. 1983;8:81–7.CrossRefPubMedGoogle Scholar
  36. Izquierdo I, Quillfeldt JA, Zanatta MS, Quevedo J, Schaeffer E, Schmitz PK, Medina JH. Sequential role of hippocampus and amygdala, entorhinal cortex and parietal cortex in formation and retrieval of memory for inhibitory avoidance in rats. Eur J Neurosci. 1997;9:786–93.CrossRefPubMedGoogle Scholar
  37. Izquierdo I, Barros DM, Mello e Souza T, de Souza MM, Izquierdo LA, Medina JH. Mechanisms for memory types differ. Nature. 1998;393:635–6.CrossRefPubMedGoogle Scholar
  38. Izquierdo I, Medina JH, Vianna MR, Izquierdo LA, Barros DM. Separate mechanisms for short- and long-term memory. Behav Brain Res. 1999;103:1–11.CrossRefPubMedGoogle Scholar
  39. Izquierdo LA, Barros DM, Vianna MR, Coitinho A, de David e Silva T, Choi H, et al. Molecular pharmacological dissection of short- and long-term memory. Cell Mol Neurobiol. 2002;22:269–87.CrossRefPubMedGoogle Scholar
  40. Jerusalinsky D, Quillfeldt JA, Walz R, Da Silva RC, Bueno e Silva M, Bianchin M, et al. Effect of the infusion of the GABA-A receptor agonist, muscimol, on the role of the entorhinal cortex, amygdala, and hippocampus in memory processes. Behav Neural Biol. 1994;61:132–8.CrossRefPubMedGoogle Scholar
  41. Kelley AE, Cador M, Stinus L. Exploration and its measurement. A psychopharmacological perspective. In: Boulton AB, Baker GB, Greenshaw AJ, editors. Neuromethods. Psychopharmacology. Clifton: Humana Press; 1989. p. 95–144.CrossRefGoogle Scholar
  42. Kesner RP, Bolland BL, Dakis M. Memory for spatial locations, motor responses, and objects: triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex. Exp Brain Res. 1993;93:462–70.CrossRefPubMedGoogle Scholar
  43. Krinke GJ. The laboratory rat. San Diego: Academic; 2000.Google Scholar
  44. Kuhn TS. The structure of scientific revolutions. 1st ed. Chicago: University of Chicago Press; 1962.Google Scholar
  45. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–84.CrossRefPubMedGoogle Scholar
  46. Maren S. Neurobiology of pavlovian fear conditioning. Annu Rev Neurosci. 2001;24:897–931.CrossRefPubMedGoogle Scholar
  47. McGaugh JL. Time-dependent processes in memory storage. Science. 1966;153:1351–8.CrossRefPubMedGoogle Scholar
  48. Melo LCS, Cruz AP, Valentim Jr SJR, Marinho AR, Mendonça JB, Nakamura-Palacios EM. Δ9-THC administered into the medial prefrontal cortex disrupts the spatial working memory. Psychopharmacology (Berl). 2005;183:54–64.CrossRefGoogle Scholar
  49. Misanin JR, Miller RR, Lewis DJ. Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace. Science. 1968;160:554–5.CrossRefPubMedGoogle Scholar
  50. Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11:47–60.CrossRefPubMedGoogle Scholar
  51. Myers KM, Davis M. Mechanisms of fear extinction. Mol Psychiatry. 2007;12:120–50.CrossRefPubMedGoogle Scholar
  52. Nader K. Memory traces unbound. Trends Neurosci. 2003a;26:65–72.CrossRefPubMedGoogle Scholar
  53. Nader K. Neuroscience: re-recording human memories. Nature. 2003b;425:571–2.CrossRefPubMedGoogle Scholar
  54. Nader K, Schafe GE, Le Doux JE. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature. 2000;406:722–6.CrossRefPubMedGoogle Scholar
  55. Nahas TR. A aprendizagem da esquiva. In: Xavier GF, editor. Técnicas para o estudo do sistema nervoso. São Paulo: Plêiade; 1999a. p. 221–41.Google Scholar
  56. Nahas TR. O teste do campo aberto. In: Xavier GF, editor. Técnicas para o estudo do sistema nervoso. São Paulo: Plêiade; 1999b. p. 203–20.Google Scholar
  57. Netto CA, Izquierdo I. On how passive is inhibitory avoidance. Behav Neural Biol. 1985;43:327–30.CrossRefPubMedGoogle Scholar
  58. Norman GR, Streiner DI. Biostatistics: the bare essentials. St. Louis: Mosby; 1994.Google Scholar
  59. Packard MG, Teather LA. Double dissociation of hippocampal and dorsal-striatal memory systems by posttraining intracerebral injections of 2-amino-5-phosphonopentanoic acid. Behav Neurosci. 1997;111:543–51.CrossRefPubMedGoogle Scholar
  60. Packard MG, Hirsh R, White NM. Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: evidence for multiple memory systems. J Neurosci. 1989;9:1465–72.PubMedGoogle Scholar
  61. Pavlov IP. Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. London: Routledge Kegan Paul; 1927.Google Scholar
  62. Paxinos G, Watson C. The rat brain in stereotaxic coordinates—the new coronal set. 5th ed. New York: Academic; 2004. p. 209.Google Scholar
  63. Pedreira ME, Maldonado H. Protein synthesis subserves reconsolidation or extinction depending on reminder duration. Neuron. 2003;38:863–9.CrossRefPubMedGoogle Scholar
  64. Przybyslawski J, Sara SJ. Reconsolidation of memory after its reactivation. Behav Brain Res. 1997;84:241–6.CrossRefPubMedGoogle Scholar
  65. Przybyslawski J, Roullet P, Sara SJ. Attenuation of emotional and nonemotional memories after their reactivation: role of beta adrenergic receptors. J Neurosci. 1999;19:6623–8.PubMedGoogle Scholar
  66. Quillfeldt JA, Zanatta MS, Schmitz PK, Quevedo J, Schaeffer E, Lima JB, Medina JH, Izquierdo I. Different brain areas are involved in memory expression at different times from training. Neurobiol Learn Mem. 1996;66:97–101.CrossRefPubMedGoogle Scholar
  67. Routtenberg A. Reverse piedpiperase: is the knockout mouse leading neuroscientists to a watery end? Trends Neurosci. 1996;19:471–2.CrossRefPubMedGoogle Scholar
  68. Russell WMS, Burch RL. The principles of humane experimental technique. London: Methuen; 1959 [reprinted by UFAW, 1992: 8 Hamilton Close, South Mimms, Potters Bar, Herts EN6 3QD England].Google Scholar
  69. Sanger DJ, Blackman DE. Operant behavior and the effects of centrally acting drugs. In: Boulton AB, Baker GB, Greenshaw AJ, editors. Neuromethods. Psychopharmacology. Clifton: Humana Press; 1989. p. 299–348.CrossRefGoogle Scholar
  70. Savonenko A, Werka T, Nikolaev E, Zielinski K, Kaczmarek L. Complex effects of NMDA receptor antagonist APV in the basolateral amygdala on acquisition of two-way avoidance reaction and long-term fear memory. Learn Mem. 2003;10:293–303.PubMedCentralCrossRefPubMedGoogle Scholar
  71. Siegel S, Castelan NJ. Nonparametric statistics. 2nd ed. Boston: McGraw-Hill; 1988.Google Scholar
  72. Skinner BF. Science and human behavior. New York: Macmillan; 1953.Google Scholar
  73. Squire LR. Memory and brain. New York: Oxford University Press; 1987.Google Scholar
  74. Squire LR, Kandel ER. Memory: from mind to molecules. New York: WH Freeman; 1999.Google Scholar
  75. Steckler T, Drinkenburg WH, Sahgal A, Aggleton JP. Recognition memory in rats—I. Concepts and classification. Prog Neurobiol. 1998;54:289–311.CrossRefPubMedGoogle Scholar
  76. Suzuki A, Josselyn SA, Frankland PW, Masushige S, Silva AJ, Kida S. Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci. 2004;24:4787–95.CrossRefPubMedGoogle Scholar
  77. Swanson LW. Brain maps: structure of the rat brain. 2nd ed. Amsterdam: Elsevier; 1998.Google Scholar
  78. Swerdlow NR, Gilbert D, Koob GF. Conditioned drug effects on spatial preference: critical evaluation. In: Boulton AB, Baker GB, Greenshaw AJ, editors. Neuromethods. Psychopharmacology. Clifton: Humana Press; 1989. p. 399–446.CrossRefGoogle Scholar
  79. Tronson NC, Taylor JR. Molecular mechanisms of memory reconsolidation. Nat Rev Neurosci. 2007;8:262–75.CrossRefPubMedGoogle Scholar
  80. Tsien JZ, Huerta PT, Tonegawa S. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell. 1996;87:1147–8.CrossRefGoogle Scholar
  81. Walker DL, Davis M. Involvement of NMDA receptors within the amygdala in short- versus long-term memory for fear conditioning as assessed with fear-potentiated startle. Behav Neurosci. 2000;114:1019–33.CrossRefPubMedGoogle Scholar
  82. Xavier GF. A aprendizagem da esquiva ii—a esquiva passiva. Ciência e Cultura. 1982;34:1587–600.Google Scholar
  83. Xavier GF, Bueno OF. On delay-of-punishment and preexposure time: effects on passive avoidance behavior in rats. Braz J Med Biol Res. 1984;17:55–64.PubMedGoogle Scholar
  84. Zar JH. Biostatistical analysis. 4th ed. Englewood Cliffs: Prentice Hall; 1999. p. 663.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of BiophysicsUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil

Personalised recommendations