Role of NCAM in Emotion and Learning

  • Lisa ConboyEmail author
  • Reto Bisaz
  • Kamila Markram
  • Carmen Sandi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 663)


NCAM is an abundant cell adhesion molecule known to be important during development. Together with its posttranslational modification consisting of the addition of the polysaccharide polysialic acid (PSA), NCAM has been classically implicated in the regulation - among other developmental functions - of neurite outgrowth and stabilization of synaptic connections. A large body of work has also demonstrated that NCAM is required in the adult brain for different behavioral functions. In this review, we focus on those studies that have shown a role of NCAM and PSA-NCAM in the regulation of emotional responses and in the learning and memory processes.


NCAM PSA-NCAM Emotion Learning Memory 


  1. 1.
    Alexinsky T, Przybyslawski J, Mileusnic R et al (1997) Antibody to day-old chick brain glycoprotein produces amnesia in adult rats. Neurobiol Learn Mem 67:14-20PubMedCrossRefGoogle Scholar
  2. 2.
    Gascon E, Vutskits L, Kiss JZ (2007) Polysialic acid-neural cell adhesion molecule in brain plasticity: from synapses to integration of new neurons. Brain Res Rev 56:101-118PubMedCrossRefGoogle Scholar
  3. 3.
    Welzl H, Stork O (2003) Cell adhesion molecules: key players in memory consolidation? News Physiol Sci 18:147-150PubMedGoogle Scholar
  4. 4.
    D’Eustachio P, Owens GC, Edelman GM et al (1985) Chromosomal location of the gene encoding the neural cell adhesion molecule (N-CAM) in the mouse. Proc Natl Acad Sci USA 82:7631-7635PubMedCrossRefGoogle Scholar
  5. 5.
    Nguyen C, Mattei MG, Mattei JF et al (1986) Localization of the human NCAM gene to band q23 of chromosome 11: the third gene coding for a cell interaction molecule mapped to the distal portion of the long arm of chromosome 11. J Cell Biol 102:711-715PubMedCrossRefGoogle Scholar
  6. 6.
    Owens GC, Edelman GM, Cunningham BA (1987) Organization of the neural cell adhesion molecule (N-CAM) gene: alternative exon usage as the basis for different membrane-associated domains. Proc Natl Acad Sci U S A 84:294-298PubMedCrossRefGoogle Scholar
  7. 7.
    Santoni MJ, Barthels D, Barbas JA et al (1987) Analysis of cDNA clones that code for the transmembrane forms of the mouse neural cell adhesion molecule (NCAM) and are generated by alternative RNA splicing. Nucleic Acids Res 15:8621-8641PubMedCrossRefGoogle Scholar
  8. 8.
    Pollerberg GE, Burridge K, Krebs KE et al (1987) The 180-kD component of the neural cell adhesion molecule N-CAM is involved in a cell-cell contacts and cytoskeleton-membrane interactions. Cell Tissue Res 250:227-236PubMedCrossRefGoogle Scholar
  9. 9.
    Rutishauser U, Jessell TM (1988) Cell adhesion molecules in vertebrate neural development. Physiol Rev 68:819-857PubMedGoogle Scholar
  10. 10.
    Bonfanti L, Olive S, Poulain DA et al (1992) Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: an immunohistochemical study. Neuroscience 49:419-436PubMedCrossRefGoogle Scholar
  11. 11.
    Theodosis DT, Bonfanti L, Olive S et al (1994) Adhesion molecules and structural plasticity of the adult hypothalamo-neurohypophysial system. Psychoneuroendocrinology 19:455-462PubMedCrossRefGoogle Scholar
  12. 12.
    Miragall F, Kadmon G, Husmann M et al (1988) Expression of cell adhesion molecules in the olfactory system of the adult mouse: presence of the embryonic form of N-CAM. Dev Biol 129:516-531PubMedCrossRefGoogle Scholar
  13. 13.
    Seki T, Arai Y (1991) Expression of highly polysialylated NCAM in the neocortex and piriform cortex of the developing and the adult rat. Anat Embryol (Berl) 184:395-401CrossRefGoogle Scholar
  14. 14.
    Varea E, Nacher J, Blasco-Ibanez JM et al (2005) PSA-NCAM expression in the rat medial prefrontal cortex. Neuroscience 136:435-443PubMedCrossRefGoogle Scholar
  15. 15.
    Cunningham BA, Hoffman S, Rutishauser U et al (1983) Molecular topography of the neural cell adhesion molecule N-CAM: surface orientation and location of sialic acid-rich and binding regions. Proc Natl Acad Sci USA 80:3116-3120PubMedCrossRefGoogle Scholar
  16. 16.
    Sadoul R, Hirn M, Deagostini-Bazin H et al (1983) Adult and embryonic mouse neural cell adhesion molecules have different binding properties. Nature 304:347-349PubMedCrossRefGoogle Scholar
  17. 17.
    Hoffman S, Edelman GM (1984) The mechanism of binding of neural cell adhesion molecules. Adv Exp Med Biol 181:147-160PubMedGoogle Scholar
  18. 18.
    Rutishauser U, Acheson A, Hall AK et al (1988) The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science 240:53-57PubMedCrossRefGoogle Scholar
  19. 19.
    Edelman GM (1984) Modulation of cell adhesion during induction, histogenesis, and perinatal development of the nervous system. Annu Rev Neurosci 7:339-377PubMedCrossRefGoogle Scholar
  20. 20.
    Edelman GM, Crossin KL (1991) Cell adhesion molecules: implications for a molecular histology. Annu Rev Biochem 60:155-190PubMedCrossRefGoogle Scholar
  21. 21.
    Cremer H, Lange R, Christoph A et al (1994) Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367:455-459PubMedCrossRefGoogle Scholar
  22. 22.
    Stork O, Welzl H, Wotjak CT et al (1999) Anxiety and increased 5-HT1A receptor response in NCAM null mutant mice. J Neurobiol 40:343-355PubMedCrossRefGoogle Scholar
  23. 23.
    Stork O, Welzl H, Cremer H et al (1997) Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecule (NCAM). Eur J Neurosci 9:1117-1125PubMedCrossRefGoogle Scholar
  24. 24.
    Stork O, Welzl H, Wolfer D et al (2000) Recovery of emotional behavior in neural cell adhesion molecule (NCAM) null mutant mice through transgenic expression of NCAM180. Eur J Neurosci 12:3291-3306PubMedCrossRefGoogle Scholar
  25. 25.
    Neiiendam JL, Kohler LB, Christensen C et al (2004) An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons. J Neurochem 91:920-935PubMedCrossRefGoogle Scholar
  26. 26.
    Rizhova L, Klementiev B, Cambon K et al (2007) Effects of P2, a peptide derived from a homophilic binding site in the neural cell adhesion molecule on learning and memory in rats. Neuroscience 149:931-942PubMedCrossRefGoogle Scholar
  27. 27.
    Kiryushko D, Kofoed T, Skladchikova G et al (2003) A synthetic peptide ligand of neural cell adhesion molecule (NCAM), C3d, promotes neuritogenesis and synaptogenesis and modulates presynaptic function in primary cultures of rat hippocampal neurons. J Biol Chem 278:12325-12334PubMedCrossRefGoogle Scholar
  28. 28.
    Hartz BP, Sohoel A, Berezin V et al (2003) A synthetic peptide ligand of NCAM affects exploratory behavior and memory in rodents. Pharmacol Biochem Behav 75:861-867PubMedCrossRefGoogle Scholar
  29. 29.
    Poltorak M, Frye MA, Wright R et al (1996) Increased neural cell adhesion molecule in the CSF of patients with mood disorder. J Neurochem 66:1532-1538PubMedCrossRefGoogle Scholar
  30. 30.
    Vawter MP (2000) Dysregulation of the neural cell adhesion molecule and neuropsychiatric disorders. Eur J Pharmacol 405(1-3):385-395PubMedCrossRefGoogle Scholar
  31. 31.
    Vawter MP, Usen N, Thatcher L et al (2001) Characterization of human cleaved N-CAM and association with schizophrenia. Exp Neurol 172:29-46PubMedCrossRefGoogle Scholar
  32. 32.
    Pillai-Nair N, Panicker AK, Rodriguiz RM et al (2005) Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior. J Neurosci 25:4659-4671PubMedCrossRefGoogle Scholar
  33. 33.
    Nacher J, Pham K, Gil-Fernandez V et al (2004) Chronic restraint stress and chronic corticosterone treatment modulate differentially the expression of molecules related to structural plasticity in the adult rat piriform cortex. Neuroscience 126:503-509PubMedCrossRefGoogle Scholar
  34. 34.
    Venero C, Tilling T, Hermans-Borgmeyer I et al (2002) Chronic stress induces opposite changes in the mRNA expression of the cell adhesion molecules NCAM and L1. Neuroscience 115:1211-1219PubMedCrossRefGoogle Scholar
  35. 35.
    Touyarot K, Sandi C (2002) Chronic restraint stress induces an isoform-specific regulation on the neural cell adhesion molecule in the hippocampus. Neural Plast 9:147-159PubMedCrossRefGoogle Scholar
  36. 36.
    Touyarot K, Venero C, Sandi C (2004) Spatial learning impairment induced by chronic stress is related to individual differences in novelty reactivity: search for neurobiological correlates. Psychoneuroendocrinology 29:290-305PubMedCrossRefGoogle Scholar
  37. 37.
    Sandi C, Touyarot K (2006) Mid-life stress and cognitive deficits during early aging in rats: individual differences and hippocampal correlates. Neurobiol Aging 27:128-140PubMedCrossRefGoogle Scholar
  38. 38.
    Sandi C, Merino JJ, Cordero MI et al (2001) Effects of chronic stress on contextual fear conditioning and the hippocampal expression of the neural cell adhesion molecule, its polysialylation, and L1. Neuroscience 102:329-339PubMedCrossRefGoogle Scholar
  39. 39.
    Pham K, Nacher J, Hof PR et al (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879-886PubMedCrossRefGoogle Scholar
  40. 40.
    Alfonso J, Frick LR, Silberman DM et al (2006) Regulation of hippocampal gene expression is conserved in two species subjected to different stressors and antidepressant treatments. Biol Psychiatry 59:244-251PubMedCrossRefGoogle Scholar
  41. 41.
    Sandi C, Loscertales M (1999) Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments. Brain Res 828:127-134PubMedCrossRefGoogle Scholar
  42. 42.
    Nacher J, Gomez-Climent MA, McEwen B (2004) Chronic non-invasive glucocorticoid administration decreases polysialylated neural cell adhesion molecule expression in the adult rat dentate gyrus. Neurosci Lett 370:40-44PubMedCrossRefGoogle Scholar
  43. 43.
    Sandi C (2004) Stress, cognitive impairment and cell adhesion molecules. Nat Rev Neurosci 5:917-930PubMedCrossRefGoogle Scholar
  44. 44.
    Cordero MI, Rodriguez JJ, Davies HA et al (2005) Chronic restraint stress down-regulates amygdaloid expression of polysialylated neural cell adhesion molecule. Neuroscience 133:903-910PubMedCrossRefGoogle Scholar
  45. 45.
    Zharkovsky A, Aonurm A, Soon K, Zharkovsky M (2006) Depression-like phenotype in NCAM-deficient mice. Int J Dev Neuroscience 24:495-603CrossRefGoogle Scholar
  46. 46.
    Encinas JM, Vaahtokari A, Enikolopov G (2006) Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci USA 103:8233-8238PubMedCrossRefGoogle Scholar
  47. 47.
    Sairanen M, O’Leary OF, Knuuttila JE et al (2007) Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat. Neuroscience 144:368-374PubMedCrossRefGoogle Scholar
  48. 48.
    Alvarez P, Squire LR (1994) Memory consolidation and the medial temporal lobe: a simple network model. Proc Natl Acad Sci USA 91:7041-7045PubMedCrossRefGoogle Scholar
  49. 49.
    Squire LR, Zola SM (1996) Structure and function of declarative and nondeclarative memory systems. Proc Natl Acad Sci USA 93:13515-13522PubMedCrossRefGoogle Scholar
  50. 50.
    Blozovski D, Harris P (1986) Passive avoidance deficits following lesions of the posteroventral hippocampo-subiculo-entorhinal area in the developing rat. J Physiol (Paris) 81:374-378Google Scholar
  51. 51.
    Moser E, Moser MB, Andersen P (1993) Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions. J Neurosci 13:3916-3925PubMedGoogle Scholar
  52. 52.
    Liang KC, McGaugh JL, Martinez JL Jr et al (1982) Post-training amygdaloid lesions impair retention of an inhibitory avoidance response. Behav Brain Res 4:237-249PubMedCrossRefGoogle Scholar
  53. 53.
    Parent MB, McGaugh JL (1994) Posttraining infusion of lidocaine into the amygdala basolateral complex impairs retention of inhibitory avoidance training. Brain Res 661:97-103PubMedCrossRefGoogle Scholar
  54. 54.
    Goosens KA, Maren S (2001) Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats. Learn Mem 8:148-155PubMedCrossRefGoogle Scholar
  55. 55.
    Wilensky AE, Schafe GE, LeDoux JE (1999) Functional inactivation of the amygdala before but not after auditory fear conditioning prevents memory formation. J Neurosci 19:RC48PubMedGoogle Scholar
  56. 56.
    Chang SD, Chen DY, Liang KC (2008) Infusion of lidocaine into the dorsal hippocampus before or after the shock training phase impaired conditioned freezing in a two-phase training task of contextual fear conditioning. Neurobiol Learn Mem 89:95-105PubMedCrossRefGoogle Scholar
  57. 57.
    Parent MB, West M, McGaugh JL (1994) Memory of rats with amygdala lesions induced 30 days after footshock-motivated escape training reflects degree of original training. Behav Neurosci 108:1080-1087PubMedCrossRefGoogle Scholar
  58. 58.
    Maren S, Yap SA, Goosens KA (2001) The amygdala is essential for the development of neuronal plasticity in the medial geniculate nucleus during auditory fear conditioning in rats. J Neurosci 21:RC135PubMedGoogle Scholar
  59. 59.
    Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106:274-285PubMedCrossRefGoogle Scholar
  60. 60.
    Bukalo O, Fentrop N, Lee AY et al (2004) Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus. J Neurosci 24:1565-1577PubMedCrossRefGoogle Scholar
  61. 61.
    Plappert CF, Schachner M, Pilz PK (2006) Neural cell adhesion molecule (NCAM) null mice show impaired sensitization of the startle response. Genes Brain Behav 5:46-52PubMedGoogle Scholar
  62. 62.
    Richardson R, Elsayed H (1998) Shock sensitization of startle in rats: the role of contextual conditioning. Behav Neurosci 112:1136-1141PubMedCrossRefGoogle Scholar
  63. 63.
    Doyle E, Nolan PM, Bell R et al (1992) Intraventricular infusions of anti-neural cell adhesion molecules in a discrete posttraining period impair consolidation of a passive avoidance response in the rat. J Neurochem 59:1570-1573PubMedCrossRefGoogle Scholar
  64. 64.
    Scholey AB, Rose SP, Zamani MR et al (1993) A role for the neural cell adhesion molecule in a late, consolidating phase of glycoprotein synthesis six hours following passive avoidance training of the young chick. Neuroscience 55:499-509PubMedCrossRefGoogle Scholar
  65. 65.
    Mileusnic R, Rose SP, Lancashire C et al (1995) Characterisation of antibodies specific for chick brain neural cell adhesion molecules which cause amnesia for a passive avoidance task. J Neurochem 64:2598-2606PubMedCrossRefGoogle Scholar
  66. 66.
    Mileusnic R, Lancashire C, Rose SP (1999) Sequence-specific impairment of memory formation by NCAM antisense oligonucleotides. Learn Mem 6:120-127PubMedGoogle Scholar
  67. 67.
    Foley AG, Hartz BP, Gallagher HC et al (2000) A synthetic peptide ligand of neural cell adhesion molecule (NCAM) IgI domain prevents NCAM internalization and disrupts passive avoidance learning. J Neurochem 74:2607-2613PubMedCrossRefGoogle Scholar
  68. 68.
    Venero C, Herrero AI, Touyarot K et al (2006) Hippocampal up-regulation of NCAM expression and polysialylation plays a key role on spatial memory. Eur J NeuroSci 23:1585-1595PubMedCrossRefGoogle Scholar
  69. 69.
    Cambon K, Venero C, Berezin V et al (2003) Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning. Neuroscience 122:183-191PubMedCrossRefGoogle Scholar
  70. 70.
    Saffell JL, Walsh FS, Doherty P (1994) Expression of NCAM containing VASE in neurons can account for a developmental loss in their neurite outgrowth response to NCAM in a cellular substratum. J Cell Biol 125:427-436PubMedCrossRefGoogle Scholar
  71. 71.
    Niethammer P, Delling M, Sytnyk V et al (2002) Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis. J Cell Biol 157:521-532PubMedCrossRefGoogle Scholar
  72. 72.
    Cambon K, Hansen SM, Venero C et al (2004) A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci 24:4197-4204PubMedCrossRefGoogle Scholar
  73. 73.
    Skibo GG, Davies HA, Rusakov DA et al (1998) Increased immunogold labelling of neural cell adhesion molecule isoforms in synaptic active zones of the chick striatum 5-6 hours after one-trial passive avoidance training. Neuroscience 82:1-5PubMedCrossRefGoogle Scholar
  74. 74.
    Pradel G, Schmidt R, Schachner M (2000) Involvement of L1.1 in memory consolidation after active avoidance conditioning in zebrafish. J Neurobiol 43:389-403PubMedCrossRefGoogle Scholar
  75. 75.
    Kandel ER (2001) The molecular biology of memory storage: a dialog between genes and synapses. Biosci Rep 21:565-611PubMedCrossRefGoogle Scholar
  76. 76.
    Pinsker HM, Hening WA, Carew TJ et al (1973) Long-term sensitization of a defensive withdrawal reflex in Aplysia. Science 182:1039-1042PubMedCrossRefGoogle Scholar
  77. 77.
    Hawkins RD, Castellucci VF, Kandel ER (1981) Interneurons involved in mediation and modulation of gill-withdrawal reflex in Aplysia. I. Identification and characterization. J Neurophysiol 45:304-314PubMedGoogle Scholar
  78. 78.
    Glanzman DL, Kandel ER, Schacher S (1989) Identified target motor neuron regulates neurite outgrowth and synapse formation of aplysia sensory neurons in vitro. Neuron 3:441-450PubMedCrossRefGoogle Scholar
  79. 79.
    Bailey CH, Chen M, Keller F et al (1992) Serotonin-mediated endocytosis of apCAM: an early step of learning-related synaptic growth in Aplysia. Science 256:645-649PubMedCrossRefGoogle Scholar
  80. 80.
    Kiss JZ, Muller D (2001) Contribution of the neural cell adhesion molecule to neuronal and synaptic plasticity. Rev Neurosci 12:297-310PubMedGoogle Scholar
  81. 81.
    Becker CG, Artola A, Gerardy-Schahn R et al (1996) The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation. J Neurosci Res 45:143-152PubMedCrossRefGoogle Scholar
  82. 82.
    Muller D, Wang C, Skibo G et al (1996) PSA-NCAM is required for activity-induced synaptic plasticity. Neuron 17:413-422PubMedCrossRefGoogle Scholar
  83. 83.
    Markram K, Gerardy-Schahn R, Sandi C (2007) Selective learning and memory impairments in mice deficient for polysialylated NCAM in adulthood. Neuroscience 144:788-796PubMedCrossRefGoogle Scholar
  84. 84.
    Florian C, Foltz J, Norreel JC et al (2006) Post-training intrahippocampal injection of synthetic poly-alpha-2, 8-sialic acid-neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice. Learn Mem 13:335-341PubMedCrossRefGoogle Scholar
  85. 85.
    Senkov O, Sun M, Weinhold B et al (2006) Polysialylated neural cell adhesion molecule is involved in induction of long-term potentiation and memory acquisition and consolidation in a fear-conditioning paradigm. J Neurosci 26:10888-10898PubMedCrossRefGoogle Scholar
  86. 86.
    Angata K, Long JM, Bukalo O et al (2004) Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs hippocampal axonal targeting and promotes fear behavior. J Biol Chem 279:32603-32613PubMedCrossRefGoogle Scholar
  87. 87.
    Markram K, Lopez Fernandez MA, Abrous DN et al (2007) Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction. Neurobiol Learn Mem 87:573-582PubMedCrossRefGoogle Scholar
  88. 88.
    Fox GB, O’Connell AW, Murphy KJ et al (1995) Memory consolidation induces a transient and time-dependent increase in the frequency of neural cell adhesion molecule polysialylated cells in the adult rat hippocampus. J Neurochem 65:2796-2799PubMedCrossRefGoogle Scholar
  89. 89.
    Doyle E, Regan CM, Shiotani T (1993) Nefiracetam (DM-9384) preserves hippocampal neural cell adhesion molecule-mediated memory consolidation processes during scopolamine disruption of passive avoidance training in the rat. J Neurochem 61:266-272PubMedCrossRefGoogle Scholar
  90. 90.
    Fox GB, Fichera G, Barry T et al (2000) Consolidation of passive avoidance learning is associated with transient increases of polysialylated neurons in layer II of the rat medial temporal cortex. J Neurobiol 45:135-141PubMedCrossRefGoogle Scholar
  91. 91.
    Foley AG, Ronn LC, Murphy KJ et al (2003) Distribution of polysialylated neural cell adhesion molecule in rat septal nuclei and septohippocampal pathway: transient increase of polysialylated interneurons in the subtriangular septal zone during memory consolidation. J Neurosci Res 74:807-817PubMedCrossRefGoogle Scholar
  92. 92.
    O’Connell AW, Fox GB, Barry T et al (1997) Spatial learning activates neural cell adhesion molecule polysialylation in a corticohippocampal pathway within the medial temporal lobe. J Neurochem 68:2538-2546PubMedCrossRefGoogle Scholar
  93. 93.
    Murphy KJ, O’Connell AW, Regan CM (1996) Repetitive and transient increases in hippocampal neural cell adhesion molecule polysialylation state following multitrial spatial training. J Neurochem 67:1268-1274PubMedCrossRefGoogle Scholar
  94. 94.
    Murphy KJ, Regan CM (1999) Sequential training in separate paradigms impairs second task consolidation and learning-associated modulations of hippocampal NCAM polysialylation. Neurobiol Learn Mem 72:28-38PubMedCrossRefGoogle Scholar
  95. 95.
    Van der Borght K, Wallinga AE, Luiten PG et al (2005) Morris water maze learning in two rat strains increases the expression of the polysialylated form of the neural cell adhesion molecule in the dentate gyrus but has no effect on hippocampal neurogenesis. Behav Neurosci 119:926-932PubMedCrossRefGoogle Scholar
  96. 96.
    Foley AG, Hedigan K, Roullet P et al (2003) Consolidation of memory for odour-reward association requires transient polysialylation of the neural cell adhesion molecule in the rat hippocampal dentate gyrus. J Neurosci Res 74:570-576PubMedCrossRefGoogle Scholar
  97. 97.
    Lopez-Fernandez MA, Montaron MF, Varea E et al (2007) Upregulation of polysialylated neural cell adhesion molecule in the dorsal hippocampus after contextual fear conditioning is involved in long-term memory formation. J Neurosci 27:4552-4561PubMedCrossRefGoogle Scholar
  98. 98.
    Merino JJ, Cordero MI, Sandi C (2000) Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity. Eur J NeuroSci 12:3283-3290PubMedCrossRefGoogle Scholar
  99. 99.
    Sandi C, Rose SP, Mileusnic R et al (1995) Corticosterone facilitates long-term memory formation via enhanced glycoprotein synthesis. Neuroscience 69:1087-1093PubMedCrossRefGoogle Scholar
  100. 100.
    Cordero MI, Merino JJ, Sandi C (1998) Correlational relationship between shock intensity and corticosterone secretion on the establishment and subsequent expression of contextual fear conditioning. Behav Neurosci 112:885-891PubMedCrossRefGoogle Scholar
  101. 101.
    Sandi C, Woodson JC, Haynes VF et al (2005) Acute stress-induced impairment of spatial memory is associated with decreased expression of neural cell adhesion molecule in the hippocampus and prefrontal cortex. Biol Psychiatry 57:856-864PubMedCrossRefGoogle Scholar
  102. 102.
    Doyle E, Nolan PM, Bell R et al (1992) Hippocampal NCAM180 transiently increases sialylation during the acquisition and consolidation of a passive avoidance response in the adult rat. J Neurosci Res 31:513-523PubMedCrossRefGoogle Scholar
  103. 103.
    Rauschecker JP (1995) Developmental plasticity and memory. Behav Brain Res 66:7-12PubMedCrossRefGoogle Scholar
  104. 104.
    O’Malley A, O’Connell C, Regan CM (1998) Ultrastructural analysis reveals avoidance conditioning to induce a transient increase in hippocampal dentate spine density in the 6 hour post-training period of consolidation. Neuroscience 87:607-613PubMedCrossRefGoogle Scholar
  105. 105.
    O’Malley A, O’Connell C, Murphy KJ et al (2000) Transient spine density increases in the mid-molecular layer of hippocampal dentate gyrus accompany consolidation of a spatial learning task in the rodent. Neuroscience 99:229-232PubMedCrossRefGoogle Scholar
  106. 106.
    Eyre MD, Richter-Levin G, Avital A et al (2003) Morphological changes in hippocampal dentate gyrus synapses following spatial learning in rats are transient. Eur J NeuroSci 17:1973-1980PubMedCrossRefGoogle Scholar
  107. 107.
    Stewart MG, Davies HA, Sandi C et al (2005) Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: a three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities. Neuroscience 131:43-54PubMedCrossRefGoogle Scholar
  108. 108.
    Dityatev A, Dityateva G, Sytnyk V et al (2004) Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J Neurosci 24:9372-9382PubMedCrossRefGoogle Scholar
  109. 109.
    Sandi C, Merino JJ, Cordero MI et al (2003) Modulation of hippocampal NCAM polysialylation and spatial memory consolidation by fear conditioning. Biol Psychiatry 54:599-607PubMedCrossRefGoogle Scholar
  110. 110.
    Doyle E, Regan CM (1993) Cholinergic and dopaminergic agents which inhibit a passive avoidance response attenuate the paradigm-specific increases in NCAM sialylation state. J Neural Transm Gen Sect 92:33-49PubMedCrossRefGoogle Scholar
  111. 111.
    Venero C, Tilling T, Hermans-Borgmeyer I et al (2004) Water maze learning and forebrain mRNA expression of the neural cell adhesion molecule L1. J Neurosci Res 75:172-181PubMedCrossRefGoogle Scholar
  112. 112.
    Arami S, Jucker M, Schachner M et al (1996) The effect of continuous intraventricular infusion of L1 and NCAM antibodies on spatial learning in rats. Behav Brain Res 81:81-87PubMedCrossRefGoogle Scholar
  113. 113.
    Sandi C, Cordero MI, Merino JJ et al (2004) Neurobiological and endocrine correlates of individual differences in spatial learning ability. Learn Mem 11:244-252PubMedCrossRefGoogle Scholar
  114. 114.
    Knafo S, Barkai E, Herrero AI et al (2005) Olfactory learning-related NCAM expression is state, time, and location specific and is correlated with individual learning capabilities. Hippocampus 15:316-325PubMedCrossRefGoogle Scholar
  115. 115.
    Gheusi G, Cremer H, McLean H et al (2000) Importance of newly generated neurons in the adult olfactory bulb for odor discrimination. Proc Natl Acad Sci USA 97:1823-1828PubMedCrossRefGoogle Scholar
  116. 116.
    Roullet P, Mileusnic R, Rose SP et al (1997) Neural cell adhesion molecules play a role in rat memory formation in appetitive as well as aversive tasks. NeuroReport 8:1907-1911PubMedCrossRefGoogle Scholar
  117. 117.
    Roullet P, Mileusnic R, Rose SP, Sara SJ et al (1997) Neural cell adhesion molecules play a role in rat memory formation in appetitive as well as aversive tasks. NeuroReport 8:1907-1911PubMedCrossRefGoogle Scholar
  118. 118.
    Conboy L, Tanrikut C, Zoladz PR, Campbell AM, Park CR, Gabriel C, Mocaer E, Sandi C, Diamond DM (2009) The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats. Int J Neuropsychopharmacol 12(3):329-41Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Lisa Conboy
    • 1
    Email author
  • Reto Bisaz
  • Kamila Markram
  • Carmen Sandi
  1. 1.Laboratory of Behavioral GeneticsBrain and Mind Institute, Swiss Federal Institute of Technology (EPFL)LausanneSwitzerland

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