Advertisement

Experimental Models and Strategies for Studying Associative Learning and Memory

  • Jin-Hui Wang
Chapter
  • 331 Downloads

Abstract

As discussed in Chap.  2, there are various memory patterns that influence cognitions and emotions in human life. It is essential to reveal the cellular and molecular mechanisms underlying the formation and retrieval of these memory patterns, which is important to develop approaches to enhance memory capacity in normal population and improve memory capability in memory-deficit patients. To fulfill this goal, animal models that mimic memory formation and retrieval, especially associative learning and memory, are needed. The most commonly used animal models in relevance to associative learning and memory include classical conditioning, operant conditioning, spatial learning, social learning, and associative memory retrieval with a reciprocal form. It is great expectation to discuss these animal models in terms of their principle, procedures, impacts, and validation. With the animal models, another critical issue is to apply comprehensive strategies to search neuronal substrates for information storage and retrieval. In order to reveal the causal relationship of molecular and cellular units in memory traces to memories, three aspects should be met: parallel changes between memory formation and memory traces are observed in a quantitative manner after associative learning; the downregulation of memory trace emergence or function attenuates memory formation being newly learned or memories previously formed; and the upregulation of neuronal substrate recruitment or function facilitates memory formation or strengthens memory previously formed. This proportional alternation between the emergence and quantity of neural substrates in memory traces and the maintenance and strength of memories grants their causal relationship. In this chapter, the author intends to review animal models and strategies that help to reveal the cellular and molecular profiles for associative learning and memory.

Keywords

Animal model Classical conditioning Operant conditioning Spatial memory and associative learning 

References

  1. 1.
    Wang J-H. Searching basic units of memory traces: associative memory cells. F1000Res. 2019;8(457):1–28.Google Scholar
  2. 2.
    Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11(1):47–60.PubMedCrossRefGoogle Scholar
  3. 3.
    Olton DS, Isaacson RL. Importance of spatial location in active avoidance tasks. J Comp Physiol Psychol. 1968;65(3):535–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Pavlov I. Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. Translated by Anrep GV. Nature. 1927;121(3052):662–4.Google Scholar
  5. 5.
    Thorndike EL. Animal intelligence: an experimental study of the associative processes in animals. Psychol Rev Monogr Suppl. 1901;2:1–109.Google Scholar
  6. 6.
    Wasserman EA, Miller RR. What’s elementary about associative learning? Annu Rev Psychol. 1997;48:573–607.CrossRefGoogle Scholar
  7. 7.
    Liu Y, et al. Piriform cortical glutamatergic and GABAergic neurons express coordinated plasticity for whisker-induced odor recall. Oncotarget. 2017;8(56):95719–40.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Wang D, et al. Neurons in the barrel cortex turn into processing whisker and odor signals: a cellular mechanism for the storage and retrieval of associative signals. Front Cell Neurosci. 2015;9:320.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Yan F, et al. Coordinated plasticity between barrel cortical glutamatergic and GABAergic neurons during associative memory. Neural Plast. 2016;2016(ID5648390):1–20.Google Scholar
  10. 10.
    Feng J, et al. Barrel cortical neuron integrates triple associated signals for their memory through receiving epigenetic-mediated new synapse innervations. Cereb Cortex. 2017;27(12):5858–71.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Rescorla RA, Wagner AR. A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement. In: Prokasy BA, editor. Classical conditioning II: current theory and research. New York: Appleton-Century; 1972.Google Scholar
  12. 12.
    Rescorla RA. Behavioral studies of Pavlovian conditioning. Annu Rev Neurosci. 1988;11:329–52.PubMedCrossRefGoogle Scholar
  13. 13.
    Rescorla RA. Pavlovian conditioning. It’s not what you think it is. Am Psychol. 1988;43(3):151–60.CrossRefGoogle Scholar
  14. 14.
    Guo R, et al. Associative memory extinction is accompanied by decayed plasticity at motor cortical neurons and persistent plasticity at sensory cortical neurons. Front Cell Neurosci. 2017;11(168):1–12.Google Scholar
  15. 15.
    Wang J-H, Guo R, Wei Z. Associative memory extinction is accompanied by decays of associative memory cells and their plasticity at motor cortex but not sensory cortex. Soc Neurosci. 2017;81(09):10385.Google Scholar
  16. 16.
    Wang J-H, et al. Both glutamatergic and gabaergic neurons are recruited to be associative memory cells. Biophys J. 2016;110(3):supplement 481a.CrossRefGoogle Scholar
  17. 17.
    Gao Z, et al. Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory. Front Cell Neurosci. 2016;10(285):1–16.Google Scholar
  18. 18.
    Wang D, et al. Neurons in the barrel cortex turn into processing whisker and odor signals: a cellular mechanism for the storage and retrieval of associative signals. Front Cell Neurosci. 2015;9(320):1–12.Google Scholar
  19. 19.
    Ehrlich I, et al. Amygdala inhibitory circuits and the control of fear memory. Neuron. 2009;62:757–71.CrossRefGoogle Scholar
  20. 20.
    Marchand A, et al. A role for anterior thalamic nuclei in contextual fear memory. Brain Struct Funct. 2014;219(5):1575–86.PubMedCrossRefGoogle Scholar
  21. 21.
    Maren S. The amygdala, synaptic plasticity, and fear memory. Ann N Y Acad Sci. 2003;985:106–13.PubMedCrossRefGoogle Scholar
  22. 22.
    Maren S, Quirk GJ. Neuronal signalling of fear memory. Nat Rev Neurosci. 2004;5(11):844–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Pape HC, Stork O. Genes and mechanisms in the amygdala involved in the formation of fear memory. Ann N Y Acad Sci. 2003;985:92–105.PubMedCrossRefGoogle Scholar
  24. 24.
    Wang JH, et al. Secondary associative memory cells and their plasticity in the prefrontal cortex. Biophys J. 2019;116(3):427a.CrossRefGoogle Scholar
  25. 25.
    Staddon JE, Cerutti DT. Operant conditioning. Annu Rev Psychol. 2003;54:115–44.PubMedCrossRefGoogle Scholar
  26. 26.
    Wang J-H, et al. Prefrontal cortical neurons are recruited as secondary associative memory cells for associative memory and cognition. Biophys J. 2018;114(3):155a.CrossRefGoogle Scholar
  27. 27.
    Wang JH, Cui S. Associative memory cells: formation, function and perspective. F1000Res. 2017;6:283.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Wang JH, Cui S. Associative memory cells and their working principle in the brain. F1000Res. 2018;7:108.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Blough DS, Millward RB. Learning: operant conditioning and verbal learning. Annu Rev Psychol. 1965;16:63–94.PubMedCrossRefGoogle Scholar
  30. 30.
    Dalla C, Shors TJ. Sex differences in learning processes of classical and operant conditioning. Physiol Behav. 2009;97(2):229–38.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Skinner BF. A discrimination without previous conditioning. Proc Natl Acad Sci U S A. 1934;20(9):532–6.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Skinner BF. The behavior of organisms: an experimental analysis. In: Skinner BF, editor. The behavior of organisms: an experimental analysis. New York: Appleton-Century-Crofts; 1938.Google Scholar
  33. 33.
    Skinner BF. Are theories of learning necessary? Psychol Rev. 1950;57(4):193–216.PubMedCrossRefGoogle Scholar
  34. 34.
    Skinner BF. Teaching machines; from the experimental study of learning come devices which arrange optimal conditions for self instruction. Science. 1958;128(3330):969–77.PubMedCrossRefGoogle Scholar
  35. 35.
    Skinner BF. The operant side of behavior therapy. J Behav Ther Exp Psychiatry. 1988;19(3):171–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Edwards S. Reinforcement principles for addiction medicine; from recreational drug use to psychiatric disorder. Prog Brain Res. 2016;223:63–76.PubMedCrossRefGoogle Scholar
  37. 37.
    Kazdin AE. In: Kazdin AE, editor. Problem-solving skills training and parent management training for oppositional defiant disorder and conduct disorder. Evidence-based psychotherapies for children and adolescents. 2nd ed. New York: Guilford Press; 2010.Google Scholar
  38. 38.
    DeLong MR. Activity of pallidal neurons during movement. J Neurophysiol. 1971;34(3):414–27.PubMedCrossRefGoogle Scholar
  39. 39.
    DeLong MR. Activity of basal ganglia neurons during movement. Brain Res. 1972;40(1):127–35.PubMedCrossRefGoogle Scholar
  40. 40.
    DeLong MR. Putamen: activity of single units during slow and rapid arm movements. Science. 1973;179(4079):1240–2.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Richardson RT, DeLong MR. Electrophysiological studies of the function of the nucleus basalis in primates. In: Napier TC, Kalivas P, Hamin I, editors. The basal forebrain: anatomy to function (Advances in experimental medicine and biology, vol. 295). New York: Plenum; 1991.Google Scholar
  42. 42.
    Mitchell SJ, et al. The primate globus pallidus: neuronal activity related to direction of movement. Exp Brain Res. 1987;68(3):491–505.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Mitchell SJ, et al. The primate nucleus basalis of Meynert: neuronal activity related to a visuomotor tracking task. Exp Brain Res. 1987;68(3):506–15.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Vitek JL, et al. Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus. Ann Neurol. 1999;46(1):22–35.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Schultz W. Predictive reward signal of dopamine neurons. J Neurophysiol. 1998;80(1):1–27.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Barnes CA. Spatial learning and memory processes: the search for their neurobiological mechanisms in the rat. Trends Neurosci. 1988;11(4):163–9.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Conrad CD. A critical review of chronic stress effects on spatial learning and memory. Prog Neuro-Psychopharmacol Biol Psychiatry. 2010;34(5):742–55.CrossRefGoogle Scholar
  48. 48.
    Foster TC. Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity. Prog Neurobiol. 2012;96(3):283–303.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Grossberg S. From brain synapses to systems for learning and memory: object recognition, spatial navigation, timed conditioning, and movement control. Brain Res. 2015;1621:270–93.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Baddeley A. Working memory: looking back and looking forward. Nat Rev Neurosci. 2003;4:829–39.PubMedCrossRefGoogle Scholar
  51. 51.
    Della Sala S, et al. Pattern span: a tool for unwelding visuo-spatial memory. Neuropsychologia. 1999;37(10):1189–99.PubMedCrossRefGoogle Scholar
  52. 52.
    Hitch GJ, et al. Competition for the focus of attention in visual working memory: perceptual recency versus executive control. Ann N Y Acad Sci. 2018;1424(1):64–75.PubMedCrossRefGoogle Scholar
  53. 53.
    Kahana MJ. The cognitive correlates of human brain oscillations. J Neurosci. 2006;26(6):1669–72.PubMedCrossRefGoogle Scholar
  54. 54.
    Becker JT, Walker JA, Olton DS. Neuroanatomical bases of spatial memory. Brain Res. 1980;200(2):307–20.PubMedCrossRefGoogle Scholar
  55. 55.
    Baddeley A, et al. The brain decade in debate: I. Neurobiology of learning and memory. Braz J Med Biol Res. 2000;33(9):993–1002.PubMedCrossRefGoogle Scholar
  56. 56.
    Bird LR, et al. Spatial memory for food hidden by rats (Rattus norvegicus) on the radial maze: studies of memory for where, what, and when. J Comp Psychol. 2003;117(2):176–87.PubMedCrossRefGoogle Scholar
  57. 57.
    Olton DS, Papas BC. Spatial memory and hippocampal function. Neuropsychologia. 1979;17(6):669–82.PubMedCrossRefGoogle Scholar
  58. 58.
    Klauer KC, Zhao Z. Double dissociations in visual and spatial short-term memory. J Exp Psychol Gen. 2004;133(3):355–81.PubMedCrossRefGoogle Scholar
  59. 59.
    Mammarella N, Cornoldi C, Donadello E. Visual but not spatial working memory deficit in children with spina bifida. Brain Cogn. 2003;53(2):311–4.PubMedCrossRefGoogle Scholar
  60. 60.
    Mammarella N, et al. Aging and intrusion errors in an active visuo-spatial working memory task. Aging Clin Exp Res. 2009;21(4–5):282–91.PubMedCrossRefGoogle Scholar
  61. 61.
    Passolunghi MC, Mammarella IC. Selective spatial working memory impairment in a group of children with mathematics learning disabilities and poor problem-solving skills. J Learn Disabil. 2012;45(4):341–50.PubMedCrossRefGoogle Scholar
  62. 62.
    Passolunghi MC, Mammarella IC, Altoe G. Cognitive abilities as precursors of the early acquisition of mathematical skills during first through second grades. Dev Neuropsychol. 2008;33(3):229–50.PubMedCrossRefGoogle Scholar
  63. 63.
    Garcia RB, et al. Visuospatial working memory for locations, colours, and binding in typically developing children and in children with dyslexia and non-verbal learning disability. Br J Dev Psychol. 2014;32(1):17–33.PubMedCrossRefGoogle Scholar
  64. 64.
    Mammarella IC, Cornoldi C. Sequence and space: the critical role of a backward spatial span in the working memory deficit of visuospatial learning disabled children. Cogn Neuropsychol. 2005;22(8):1055–68.PubMedCrossRefGoogle Scholar
  65. 65.
    Lancia S, et al. Are ventrolateral and dorsolateral prefrontal cortices involved in the computerized Corsi block-tapping test execution? An fNIRS study. Neurophotonics. 2018;5(1):011019.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Thomas E, et al. Spatial sequence memory and spatial error monitoring in the Groton Maze Learning Task (GMLT): a validation study of GMLT sub-measures in healthy children. Child Neuropsychol. 2016;22(7):837–52.PubMedCrossRefGoogle Scholar
  67. 67.
    Pickering SJ, et al. Development of memory for pattern and path: further evidence for the fractionation of visuo-spatial memory. Q J Exp Psychol A. 2001;54(2):397–420.PubMedCrossRefGoogle Scholar
  68. 68.
    Guariglia CC. Spatial working memory in Alzheimer’s disease: a study using the Corsi block-tapping test. Dement Neuropsychol. 2007;1(4):392–5.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Moscovitch M, et al. The cognitive neuroscience of remote episodic, semantic and spatial memory. Curr Opin Neurobiol. 2006;16(2):179–90.PubMedCrossRefGoogle Scholar
  70. 70.
    Olton DS. Spatial memory. Sci Am. 1977;236(6):82–4. 89–94, 96, 98.CrossRefGoogle Scholar
  71. 71.
    O’Keefe J, Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 1971;34(1):171–5.PubMedCrossRefGoogle Scholar
  72. 72.
    O’Keefe J. Hippocampus, theta, and spatial memory. Curr Opin Neurobiol. 1993;3(6):917–24.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Squire LR, et al. Activation of the hippocampus in normal humans: a functional anatomical study of memory. Proc Natl Acad Sci U S A. 1992;89(5):1837–41.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Squire LR. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev. 1992;99(2):195–231.PubMedCrossRefGoogle Scholar
  75. 75.
    Martin SJ, de Hoz L, Morris RG. Retrograde amnesia: neither partial nor complete hippocampal lesions in rats result in preferential sparing of remote spatial memory, even after reminding. Neuropsychologia. 2005;43(4):609–24.PubMedCrossRefGoogle Scholar
  76. 76.
    Milner B, Penfield W. The effect of hippocampal lesions on recent memory. Trans Am Neurol Assoc. 1955;(80th Meeting): 42–8.Google Scholar
  77. 77.
    Moser MB, Moser EI. Distributed encoding and retrieval of spatial memory in the hippocampus. J Neurosci. 1998;18(18):7535–42.PubMedCrossRefGoogle Scholar
  78. 78.
    Penfield W. Observations on the anatomy of memory. Folia Psychiatr Neurol Neurochir Neerl. 1950;53(2):349–51.PubMedGoogle Scholar
  79. 79.
    Squire LR, Knowlton B, Musen G. The structure and organization of memory. Annu Rev Psychol. 1993;44:453–95.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Squire LR, McKee R. Influence of prior events on cognitive judgments in amnesia. J Exp Psychol Learn Mem Cogn. 1992;18(1):106–15.PubMedCrossRefGoogle Scholar
  81. 81.
    McGaugh JL. Memory – a century of consolidation. Science. 2000;287(5451):248–51.PubMedCrossRefGoogle Scholar
  82. 82.
    Maguire EA, Frackowiak RS, Frith CD. Recalling routes around London: activation of the right hippocampus in taxi drivers. J Neurosci. 1997;17(18):7103–10.PubMedCrossRefGoogle Scholar
  83. 83.
    Brun VH, et al. Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry. Science. 2002;296(5576):2243–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Goodrich-Hunsaker NJ, Hunsaker MR, Kesner RP. The interactions and dissociations of the dorsal hippocampus subregions: how the dentate gyrus, CA3, and CA1 process spatial information. Behav Neurosci. 2008;122(1):16–26.PubMedCrossRefGoogle Scholar
  85. 85.
    Saab BJ, et al. NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory. Neuron. 2009;63(5):643–56.PubMedCrossRefGoogle Scholar
  86. 86.
    Cho YH, Kesner RP. Involvement of entorhinal cortex or parietal cortex in long-term spatial discrimination memory in rats: retrograde amnesia. Behav Neurosci. 1996;110(3):436–42.PubMedCrossRefGoogle Scholar
  87. 87.
    Colby CL, Goldberg ME. Space and attention in parietal cortex. Annu Rev Neurosci. 1999;22:319–49.PubMedCrossRefGoogle Scholar
  88. 88.
    Kesner RP, Holbrook T. Dissociation of item and order spatial memory in rats following medial prefrontal cortex lesions. Neuropsychologia. 1987;25(4):653–64.PubMedCrossRefGoogle Scholar
  89. 89.
    Liu P, Bilkey DK. The effect of excitotoxic lesions centered on the hippocampus or perirhinal cortex in object recognition and spatial memory tasks. Behav Neurosci. 2001;115(1):94–111.PubMedCrossRefGoogle Scholar
  90. 90.
    Sasaki T, Leutgeb S, Leutgeb JK. Spatial and memory circuits in the medial entorhinal cortex. Curr Opin Neurobiol. 2015;32:16–23.PubMedCrossRefGoogle Scholar
  91. 91.
    Save E, Moghaddam M. Effects of lesions of the associative parietal cortex on the acquisition and use of spatial memory in egocentric and allocentric navigation tasks in the rat. Behav Neurosci. 1996;110(1):74–85.PubMedCrossRefGoogle Scholar
  92. 92.
    Witter MP, Moser EI. Spatial representation and the architecture of the entorhinal cortex. Trends Neurosci. 2006;29(12):671–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Wirt RA, Hyman JM. Integrating spatial working memory and remote memory: interactions between the medial prefrontal cortex and hippocampus. Brain Sci. 2017;7(4).PubMedCentralCrossRefPubMedGoogle Scholar
  94. 94.
    Kesner RP. The posterior parietal cortex and long-term memory representation of spatial information. Neurobiol Learn Mem. 2009;91(2):197–206.PubMedCrossRefGoogle Scholar
  95. 95.
    Lee I, Kesner RP. Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory. Nat Neurosci. 2002;5(2):162–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Morris RG, et al. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature. 1986;319:774–6.PubMedCrossRefGoogle Scholar
  97. 97.
    Morris RG. Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5. J Neurosci. 1989;9(9):3040–57.PubMedCrossRefGoogle Scholar
  98. 98.
    Wang JH, et al. Upregulation of glutamatergic receptor-channels is associated with cross-modal reflexes encoded in barrel cortex and piriform cortex. Biophys J. 2014;106(2):supplement 191a.CrossRefGoogle Scholar
  99. 99.
    Aronoff R, et al. Long-range connectivity of mouse primary somatosensory barrel cortex. Eur J Neurosci. 2010;31(12):2221–33.PubMedCrossRefGoogle Scholar
  100. 100.
    Haberly LB, et al. Distribution and ultrastructure of neurons in opossum piriform cortex displaying immunoreactivity to GABA and GAD and high-affinity tritiated GABA uptake. J Comp Neurol. 1987;266(2):269–90.PubMedCrossRefGoogle Scholar
  101. 101.
    Petersen CCH. Functional organization of the barrel cortex. Neuron. 2007;56:339–55.PubMedCrossRefGoogle Scholar
  102. 102.
    Barkai E, Saar D. Cellular correlates of olfactory learning in the rat piriform cortex. Rev Neurosci. 2001;12(2):111–20.PubMedCrossRefGoogle Scholar
  103. 103.
    Wilson DA. Receptive fields in the rat piriform cortex. Chem Senses. 2001;26(5):577–84.PubMedCrossRefGoogle Scholar
  104. 104.
    Wilson DA, Sullivan RM. Cortical processing of odor objects. Neuron. 2012;72(4):506–19.CrossRefGoogle Scholar
  105. 105.
    Ni H, et al. Upregulation of barrel GABAergic neurons is associated with cross-modal plasticity in olfactory deficit. PLoS One. 2010;5(10):e13736.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Ye B, et al. The functional upregulation of piriform cortex is associated with cross-modal plasticity in loss of whisker tactile inputs. PLoS One. 2012;7(8):e41986.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Zhang G, et al. Upregulation of excitatory neurons and downregulation of inhibitory neurons in barrel cortex are associated with loss of whisker inputs. Mol Brain. 2013;6(1):2.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Zhao X, et al. Coordinated plasticity among glutamatergic and GABAergic neurons and synapses in the barrel cortex is correlated to learning efficiency. Front Cell Neurosci. 2017;11(221):1–12.Google Scholar
  109. 109.
    Liu Y, et al. Activity strengths of cortical glutamatergic and GABAergic neurons are correlated with transgenerational inheritance of learning ability. Oncotarget. 2017;8(68):112401–16.PubMedPubMedCentralGoogle Scholar
  110. 110.
    Lei Z, et al. Synapse innervation and associative memory cell are recruited for integrative storage of whisker and odor signals in the barrel cortex through miRNA-mediated processes. Front Cell Neurosci. 2017;11(316):1–11.Google Scholar
  111. 111.
    Asok A, et al. Molecular mechanisms of the memory trace. Trends Neurosci. 2019;42(1):14–22.PubMedCrossRefGoogle Scholar
  112. 112.
    Dubnau J, Chiang AS, Tully T. Neural substrates of memory: from synapse to system. J Neurobiol. 2003;54(1):238–53.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Josselyn SA, Kohler S, Frankland PW. Finding the engram. Nat Rev Neurosci. 2015;16(9):521–34.PubMedCrossRefGoogle Scholar
  114. 114.
    Josselyn SA, Kohler S, Frankland PW. Heroes of the engram. J Neurosci. 2017;37(18):4647–57.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Lisman J, et al. Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability. Nat Neurosci. 2018;21(3):309–14.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Semon RW. In: Semon RW, editor. Mnemic psychology. London: Allen, Unwin; 1923.Google Scholar
  117. 117.
    McGaugh JL. The search for the memory trace. Ann N Y Acad Sci. 1972;193:112–23.PubMedCrossRefGoogle Scholar
  118. 118.
    McClelland JL, McNaughton BL, O’Reilly RC. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol Rev. 1995;102(3):419–57.PubMedCrossRefGoogle Scholar
  119. 119.
    Hebb DO. Spontaneous neurosis in chimpanzees; theoretical relations with clinical and experimental phenomena. Psychosom Med. 1947;9(1):3–19.PubMedCrossRefGoogle Scholar
  120. 120.
    Penfield W. Bilateral frontal gyrectomy and postoperative intelligence. Res Publ Assoc Res Nerv Ment Dis. 1948;27(1 vol.):519–34.PubMedGoogle Scholar
  121. 121.
    Lashley KS. Mass action in cerebral function. Science. 1931;73(1888):245–54.PubMedCrossRefGoogle Scholar
  122. 122.
    Lashley KS. Structural variation in the nervous system in relation to behavior. Psychol Rev. 1947;54(6):325–34.PubMedCrossRefGoogle Scholar
  123. 123.
    Hebb DO. The organization of behavior, a neuropsychological theory. New York: Wiley; 1949.Google Scholar
  124. 124.
    Hebb DO. Animal and physiological psychology. Annu Rev Psychol. 1950;1:173–88.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Bliss TVP, Lynch MA. Long-term potentiation of synaptic transmission in the hippocampus: properties and mechanisms. In: Landfield PW, Deadwyler SA, editors. Long-term potentiation: from biophysics to behavior. New York: Alan R. Liss; 1988. p. 3–72.Google Scholar
  126. 126.
    Hodgkin AL, Huxley AF. Action potentials recorded from inside a nerve fiber. Nature. 1939;144:710–1.CrossRefGoogle Scholar
  127. 127.
    Feng TP. Studies on the neuromuscular junction. XXVI. The changes of the end-plate potentail during and after prolonged stimulation. Chin J Physiol. 1941;16:341–72.Google Scholar
  128. 128.
    Feng TP. Looking back, looking forward. Annu Rev Neurosci. 1988;11:1–12.PubMedCrossRefGoogle Scholar
  129. 129.
    Zhao J, Wang D, Wang JH. Barrel cortical neurons and astrocytes coordinately respond to an increased whisker stimulus frequency. Mol Brain. 2012;5:12.PubMedPubMedCentralGoogle Scholar
  130. 130.
    Buzsaki G. Network properties of memory trace formation in the hippocampus. Boll Soc Ital Biol Sper. 1991;67(9):817–35.PubMedGoogle Scholar
  131. 131.
    Jones MW, Wilson MA. Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory task. PLoS Biol. 2005;3(12):e402.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Khodagholy D, Gelinas JN, Buzsaki G. Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus. Science. 2017;358(6361):369–72.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Rothschild G, Eban E, Frank LM. A cortical-hippocampal-cortical loop of information processing during memory consolidation. Nat Neurosci. 2017;20(2):251–9.PubMedCrossRefGoogle Scholar
  134. 134.
    Lansink CS, et al. Hippocampus leads ventral striatum in replay of place-reward information. PLoS Biol. 2009;7(8):e1000173.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Takehara-Nishiuchi K, McNaughton BL. Spontaneous changes of neocortical code for associative memory during consolidation. Science. 2008;322(5903):960–3.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Girardeau G, Inema I, Buzsaki G. Reactivations of emotional memory in the hippocampus-amygdala system during sleep. Nat Neurosci. 2017;20(11):1634–42.CrossRefGoogle Scholar
  137. 137.
    Katkov M, Romani S, Tsodyks M. Memory retrieval from first principles. Neuron. 2017;94(5):1027–32.PubMedCrossRefGoogle Scholar
  138. 138.
    Jahans-Price T, et al. Computational modeling and analysis of hippocampal-prefrontal information coding during a spatial decision-making task. Front Behav Neurosci. 2014;8:62.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Lansner A. Associative memory models: from the cell-assembly theory to biophysically detailed cortex simulations. Trends Neurosci. 2009;32(3):178–86.PubMedCrossRefGoogle Scholar
  140. 140.
    Schwindel CD, McNaughton BL. Hippocampal-cortical interactions and the dynamics of memory trace reactivation. Prog Brain Res. 2011;193:163–77.PubMedCrossRefGoogle Scholar
  141. 141.
    Bracha V, et al. The cerebellum and eye-blink conditioning: learning versus network performance hypotheses. Neuroscience. 2009;162(3):787–96.PubMedCrossRefGoogle Scholar
  142. 142.
    Burhans LB, Smith-Bell C, Schreurs BG. Conditioning-specific reflex modification of the rabbit’s nictitating membrane response and heart rate: behavioral rules, neural substrates, and potential applications to posttraumatic stress disorder. Behav Neurosci. 2008;122(6):1191–206.PubMedCrossRefGoogle Scholar
  143. 143.
    Davis M, et al. Fear-potentiated startle: a neural and pharmacological analysis. Behav Brain Res. 1993;58(1–2):175–98.PubMedCrossRefGoogle Scholar
  144. 144.
    Glanzman DL. The cellular basis of classical conditioning in Aplysia californica – it’s less simple than you think. Trends Neurosci. 1995;18(1):30–6.PubMedCrossRefGoogle Scholar
  145. 145.
    Hawkins RD. A cellular mechanism of classical conditioning in Aplysia. J Exp Biol. 1984;112:113–28.PubMedGoogle Scholar
  146. 146.
    Lechner HA, Baxter DA, Byrne JH. Classical conditioning of feeding in Aplysia: I. Behavioral analysis. J Neurosci. 2000;20(9):3369–76.PubMedCrossRefGoogle Scholar
  147. 147.
    Maren S. Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats. Eur J Neurosci. 2008;28(8):1661–6.PubMedCrossRefGoogle Scholar
  148. 148.
    Pennypacker HS, et al. An apparatus and procedure for conditioning the eye-blink reflex in the squirrel monkey. J Exp Anal Behav. 1966;9(5):601–4.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Perkowski JJ, Murphy GG. Deletion of the mouse homolog of KCNAB2, a gene linked to monosomy 1p36, results in associative memory impairments and amygdala hyperexcitability. J Neurosci. 2011;31(1):46–54.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Reijmers LG, et al. Localization of a stable neural correlate of associative memory. Science. 2007;317(5842):1230–3.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Sears RJ, Baker JS, Frey PW. The eye blink as a time-locked response: implications for serial and second-order conditioning. J Exp Psychol Anim Behav Process. 1979;5(1):43–64.PubMedCrossRefGoogle Scholar
  152. 152.
    Theios J, Brelsford JW Jr. A Markov model for classical conditioning: application to eye-blink conditioning in rabbits. Psychol Rev. 1966;73(5):393–408.PubMedCrossRefGoogle Scholar
  153. 153.
    Woodruff-Pak DS, Disterhoft JF. Where is the trace in trace conditioning? Trends Neurosci. 2008;31(2):105–12.PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Martinez M, Calvo-Torrent A, Pico-Alfonso MA. Social defeat and subordination as models of social stress in laboratory rodents: a review. Aggress Behav. 1998;24:241–56.CrossRefGoogle Scholar
  155. 155.
    Tsankova NM, et al. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006;9(4):519–25.PubMedCrossRefGoogle Scholar
  156. 156.
    Vasconcelos M, Stein DJ, de Almeida RM. Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade. Trends Psychiatry Psychother. 2015;37(2):51–66.PubMedCrossRefGoogle Scholar
  157. 157.
    Wang J-H, et al. Neurons in barrel cortex turn into processing whisker and odor signals: a novel form of associative learning. Soc Neurosci. 2013;653(14):WW11.Google Scholar
  158. 158.
    Carr MF, Jadhav SP, Frank LM. Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Nat Neurosci. 2011;14(2):147–53.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Harris KD, et al. Organization of cell assemblies in the hippocampus. Nature. 2003;424(6948):552–6.CrossRefGoogle Scholar
  160. 160.
    Ji D, Wilson MA. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci. 2007;10(1):100–7.CrossRefGoogle Scholar
  161. 161.
    Jadhav SP, et al. Awake hippocampal sharp-wave ripples support spatial memory. Science. 2012;336(6087):1454–8.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Kay K, et al. A hippocampal network for spatial coding during immobility and sleep. Nature. 2016;531(7593):185–90.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Kudrimoti HS, Barnes CA, McNaughton BL. Reactivation of hippocampal cell assemblies: effects of behavioral state, experience, and EEG dynamics. J Neurosci. 1999;19(10):4090–101.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    McNaughton BL, Barnes CA, O’Keefe J. The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats. Exp Brain Res. 1983;52(1):41–9.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Penfield W, Perot P. The brain’s record of auditory and visual experience. A final summary and discussion. Brain. 1963;86:595–696.PubMedCrossRefGoogle Scholar
  166. 166.
    Sirota A, et al. Communication between neocortex and hippocampus during sleep in rodents. Proc Natl Acad Sci U S A. 2003;100(4):2065–9.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Skaggs WE, McNaughton BL. Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science. 1996;271(5257):1870–3.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Wilson MA, McNaughton BL. Dynamics of the hippocampal ensemble code for space. Science. 1993;261(5124):1055–8.CrossRefGoogle Scholar
  169. 169.
    Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science. 1994;265(5172):676–9.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Wirth S, et al. Single neurons in the monkey hippocampus and learning of new associations. Science. 2003;300(5625):1578–81.CrossRefGoogle Scholar
  171. 171.
    Yu JY, et al. Specific hippocampal representations are linked to generalized cortical representations in memory. Nat Commun. 2018;9(1):2209.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Yokose J, et al. Overlapping memory trace indispensable for linking, but not recalling, individual memories. Science. 2017;355(6323):398–403.CrossRefGoogle Scholar
  173. 173.
    Varela C, et al. Anatomical substrates for direct interactions between hippocampus, medial prefrontal cortex, and the thalamic nucleus reuniens. Brain Struct Funct. 2014;219(3):911–29.PubMedCrossRefGoogle Scholar
  174. 174.
    Nikolenko V, Poskanzer KE, Yuste R. Two-photon photostimulation and imaging of neural circuits. Nat Methods. 2007;4(11):943–50.CrossRefGoogle Scholar
  175. 175.
    Stosiek C, et al. In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci USA. 2003;100(12):7319–24.PubMedCrossRefGoogle Scholar
  176. 176.
    Wang KH, et al. In vivo two-photon imaging reveals a role of arc in enhancing orientation specificity in visual cortex. Cell. 2006;126(2):389–402.CrossRefGoogle Scholar
  177. 177.
    Mao D, et al. Hippocampus-dependent emergence of spatial sequence coding in retrosplenial cortex. Proc Natl Acad Sci U S A. 2018;115(31):8015–8.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Fu M, et al. Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature. 2012;483(7387):92–5.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Sugiura H, et al. Transducing neuronal activity into dendritic spine morphology: new roles for p38 MAP kinase and N-cadherin. Neuroscientist. 2009;15(1):90–104.PubMedCrossRefGoogle Scholar
  180. 180.
    Thiagarajan TC, Piedras-Renteria ES, Tsien RW. Alpha- and beta-CaMKII. Inverse regulation by neuronal activity and opposing effects on synaptic strength. Neuron. 2002;36:1103–14.PubMedCrossRefGoogle Scholar
  181. 181.
    Wong-Riley MT. Cytochrome oxidase: an endogenous metabolic maker for neuronal activity. Trends Neurosci. 1989;12(3):94–101.PubMedCrossRefGoogle Scholar
  182. 182.
    Morgan JI, Curran T. Stimulus-transcription coupling in neurons: role of cellular immediate-early genes. Trends Neurosci. 1989;12(11):459–62.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Link W, et al. Somatodendritic expression of an immediate early gene is regulated by synaptic activity. Proc Natl Acad Sci U S A. 1995;92(12):5734–8.PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Guzowski JF, et al. Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles. Nat Neurosci. 1999;2(12):1120–4.PubMedCrossRefGoogle Scholar
  185. 185.
    Tayler KK, et al. Reactivation of neural ensembles during the retrieval of recent and remote memory. Curr Biol. 2013;23(2):99–106.CrossRefGoogle Scholar
  186. 186.
    Bissiere S, et al. Electrical synapses control hippocampal contributions to fear learning and memory. Science. 2011;331(6013):87–91.PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Grundemann J, Luthi A. Ensemble coding in amygdala circuits for associative learning. Curr Opin Neurobiol. 2015;35:200–6.PubMedCrossRefGoogle Scholar
  188. 188.
    Tanaka KZ, McHugh TJ. The hippocampal engram as a memory index. J Exp Neurosci. 2018;12:1179069518815942.PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Tonegawa S, et al. Memory engram cells have come of age. Neuron. 2015;87(5):918–31.PubMedCrossRefGoogle Scholar
  190. 190.
    Kiessling M, Gass P. Immediate early gene expression in experimental epilepsy. Brain Pathol. 1993;3(4):381–93.PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Meldrum BS. Concept of activity-induced cell death in epilepsy: historical and contemporary perspectives. Prog Brain Res. 2002;135:3–11.CrossRefGoogle Scholar
  192. 192.
    Wang X, et al. Persistent hyperactivity of hippocampal dentate interneurons after a silent period in the rat pilocarpine model of epilepsy. Front Cell Neurosci. 2016;10:94.PubMedPubMedCentralGoogle Scholar
  193. 193.
    Simonato M, et al. Differential expression of immediate early genes in the hippocampus in the kindling model of epilepsy. Brain Res Mol Brain Res. 1991;11(2):115–24.CrossRefGoogle Scholar
  194. 194.
    Abe H, Nowak TS Jr. Induced hippocampal neuron protection in an optimized gerbil ischemia model: insult thresholds for tolerance induction and altered gene expression defined by ischemic depolarization. J Cereb Blood Flow Metab. 2004;24(1):84–97.PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Bokesch PM, et al. Dextromethorphan inhibits ischemia-induced c-fos expression and delayed neuronal death in hippocampal neurons. Anesthesiology. 1994;81(2):470–7.CrossRefGoogle Scholar
  196. 196.
    Kiessling M, et al. Differential transcription and translation of immediate early genes in the gerbil hippocampus after transient global ischemia. J Cereb Blood Flow Metab. 1993;13(6):914–24.PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Sossin WS. Molecular memory traces. Prog Brain Res. 2008;169:3–25.PubMedCrossRefGoogle Scholar
  198. 198.
    Milo R. What is the total number of protein molecules per cell volume? A call to rethink some published values. BioEssays. 2013;35(12):1050–5.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Lashley KS. Cerebral organization and behavior. Res Publ Assoc Res Nerv Ment Dis. 1958;36:1–4; discussion 14–18PubMedGoogle Scholar
  200. 200.
    Penfield W, Milner B. Memory deficit produced by bilateral lesions in the hippocampal zone. AMA Arch Neurol Psychiatry. 1958;79(5):475–97.PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Penfield W. Engrams in the human brain. Mechanisms of memory. Proc R Soc Med. 1968;61(8):831–40.PubMedPubMedCentralGoogle Scholar
  202. 202.
    Flexner JB, Flexner LB, Stellar E. Memory in mice as affected by intracerebral puromycin. Science. 1963;141(3575):57–9.PubMedCrossRefPubMedCentralGoogle Scholar
  203. 203.
    Flexner LB, Flexner JB, Roberts RB. Memory in mice analyzed with antibiotics. Antibiotics are useful to study stages of memory and to indicate molecular events which sustain memory. Science. 1967;155(3768):1377–83.PubMedCrossRefPubMedCentralGoogle Scholar
  204. 204.
    Flexner JB, Glexner LB. Studies on memory: evidence for a widespread memory trace in the neocortex after the suppression of recent memory by puromycin. Proc Natl Acad Sci U S A. 1969;62(3):729–32.PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Silva AJ, et al. Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science. 1992;257(10 July):206–11.PubMedCrossRefPubMedCentralGoogle Scholar
  206. 206.
    Liu X, et al. Identification and manipulation of memory engram cells. Cold Spring Harb Symp Quant Biol. 2014;79:59–65.PubMedCrossRefPubMedCentralGoogle Scholar
  207. 207.
    Ramirez S, Tonegawa S, Liu X. Identification and optogenetic manipulation of memory engrams in the hippocampus. Front Behav Neurosci. 2013;7:226.PubMedPubMedCentralGoogle Scholar
  208. 208.
    Penfield W. Some mechanisms of consciousness discovered during electrical stimulation of the brain. Proc Natl Acad Sci U S A. 1958;44(2):51–66.PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Rasmussen T, Penfield W. The human sensorimotor cortex as studied by electrical stimulation. Fed Proc. 1947;6(1 Pt 2):184.PubMedPubMedCentralGoogle Scholar
  210. 210.
    Penfield W, Welch K. Instability of response to stimulation of the sensorimotor cortex of man. J Physiol. 1949;109(3–4):358–65, illustPubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Ferry B, Roozendaal B, McGaugh JL. Role of norepinephrine in mediating stress hormone regulation of long-term memory storage: a critical involvement of the amygdala. Biol Psychiatry. 1999;46(9):1140–52.PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    Meneses A, Liy-Salmeron G. Serotonin and emotion, learning and memory. Rev Neurosci. 2012;23(5–6):543–53.PubMedPubMedCentralGoogle Scholar
  213. 213.
    Liu X, et al. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature. 2012;484(7394):381–5.PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Liu X, Ramirez S, Tonegawa S. Inception of a false memory by optogenetic manipulation of a hippocampal memory engram. Philos Trans R Soc Lond Ser B Biol Sci. 2014;369(1633):20130142.CrossRefGoogle Scholar
  215. 215.
    Roy DS, et al. Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease. Nature. 2016;531(7595):508–12.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Ramirez S, et al. Creating a false memory in the hippocampus. Science. 2013;341(6144):387–91.PubMedCrossRefGoogle Scholar
  217. 217.
    Ramirez S, et al. Activating positive memory engrams suppresses depression-like behaviour. Nature. 2015;522(7556):335–9.PubMedPubMedCentralCrossRefGoogle Scholar
  218. 218.
    Ryan TJ, et al. Memory. Engram cells retain memory under retrograde amnesia. Science. 2015;348(6238):1007–13.PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Cabeza R, et al. The parietal cortex and episodic memory: an attentional account. Nat Rev Neurosci. 2008;9(8):613–25.PubMedPubMedCentralCrossRefGoogle Scholar
  220. 220.
    Poo MM, et al. What is memory? The present state of the engram. BMC Biol. 2016;14:40.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Jin-Hui Wang
    • 1
  1. 1.University of Chinese Academy of SciencesBeijingChina

Personalised recommendations