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Regulation of Immediate Early Genes in the Visual Cortex

  • Raphael Pinaud
  • Thomas A. Terleph
  • R. William Currie
  • Liisa A. Tremere

Keywords

Visual Cortex Cortical Layer Visual Deprivation Ocular Dominance Column Supragranular Layer 
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.

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References

  1. Angel P, Karin M (1991). The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072: 129–157.PubMedGoogle Scholar
  2. Arckens L (2005). The molecular biology of sensory map plasticity in adult mammals. In: Plasticity in the Visual system: From Genes to Circuits (Pinaud R, Tremere LA, DeWeerd P, eds), pp. 181–203. New York: Springer-Verlag.Google Scholar
  3. Arckens L, Van Der Gucht E, Eysel UT, Orban GA, Vandesande F (2000). Investigation of cortical reorganization in area 17 and nine extrastriate visual areas through the detection of changes in immediate early gene expression as induced by retinal lesions. J Comp Neurol 425: 531–544.PubMedGoogle Scholar
  4. Beaulieu C, Colonnier M (1987). Effect of the richness of the environment on the cat visual cortex. J Comp Neurol 266: 478–494.PubMedGoogle Scholar
  5. Beaulieu C, Colonnier M (1988). Richness of environment affects the number of contacts formed by boutons containing flat vesicles but does not alter the number of these boutons per neuron. J Comp Neurol 274: 347–356.PubMedGoogle Scholar
  6. Beaulieu C, Cynader M (1990a). Effect of the richness of the environment on neurons in cat visual cortex. II. Spatial and temporal frequency characteristics. Brain Res Dev Brain Res 53: 82–88.PubMedGoogle Scholar
  7. Beaulieu C, Cynader M (1990b). Effect of the richness of the environment on neurons in cat visual cortex. I. Receptive field properties. Brain Res Dev Brain Res 53: 71–81.PubMedGoogle Scholar
  8. Beaver CJ, Mitchell DE, Robertson HA (1993). Immunohistochemical study of the pattern of rapid expression of C-Fos protein in the visual cortex of dark-reared kittens following initial exposure to light. J Comp Neurol 333: 469–484.PubMedGoogle Scholar
  9. Bhide PG, Bedi KS (1984). The effects of a lengthy period of environmental diversity on well-fed and previously undernourished rats. II. Synapse-to-neuron ratios. J Comp Neurol 227: 305–310.PubMedGoogle Scholar
  10. Bhide PG, Bedi KS (1985). The effects of a 30 day period of environmental diversity on well-fed and previously undernourished rats: neuronal and synaptic measures in the visual cortex (area 17). J Comp Neurol 236: 121–126.PubMedGoogle Scholar
  11. Caleo M, Lodovichi C, Pizzorusso T, Maffei L (1999). Expression of the transcription factor Zif268 in the visual cortex of monocularly deprived rats: effects of nerve growth factor. Neuroscience 91: 1017–1026.PubMedGoogle Scholar
  12. Carrasco-Serrano C, Viniegra S, Ballesta JJ, Criado M (2000). Phorbol ester activation of the neuronal nicotinic acetylcholine receptor alpha7 subunit gene: involvement of transcription factor Egr-1. J Neurochem 74: 932–939.PubMedGoogle Scholar
  13. Chaudhuri A, Cynader MS (1993). Activity-dependent expression of the transcription factor Zif268 reveals ocular dominance columns in monkey visual cortex. Brain Res 605: 349–353.PubMedGoogle Scholar
  14. Chaudhuri A, Matsubara JA, Cynader MS (1995). Neuronal activity in primate visual cortex assessed by immunostaining for the transcription factor Zif268. Vis Neurosci 12: 35–50.PubMedGoogle Scholar
  15. Cirelli C, Pompeiano M, Tononi G (1996). Neuronal gene expression in the waking state: a role for the locus coeruleus. Science 274: 1211–1215.PubMedGoogle Scholar
  16. Collingridge GL, Lester RA (1989). Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev 41: 143–210.PubMedGoogle Scholar
  17. Correa-Lacarcel J, Pujante MJ, Terol FF, Almenar-Garcia V, Puchades-Orts A, Ballesta JJ, Lloret J, Robles JA, Sanchez-del-Campo F (2000). Stimulus frequency affects c-fos expression in the rat visual system. J Chem Neuroanat 18: 135–146.PubMedGoogle Scholar
  18. Darian-Smith C, Gilbert CD (1994). Axonal sprouting accompanies functional reorganization in adult cat striate cortex. Nature 368: 737–740.PubMedGoogle Scholar
  19. Daw NW, Fox K, Sato H, Czepita D (1992). Critical period for monocular deprivation in the cat visual cortex. J Neurophysiol 67: 197–202.PubMedGoogle Scholar
  20. Evarts EV (1968). A technique for recording activity of subcortical neurons in moving animals. Electroencephalogr Clin Neurophysiol 24: 83–86.PubMedGoogle Scholar
  21. Fanselow EE, Sameshima K, Baccala LA, Nicolelis MA (2001). Thalamic bursting in rats during different awake behavioral states. Proc Natl Acad Sci USA 98: 15330–15335.PubMedGoogle Scholar
  22. Finkbeiner S, Greenberg ME (1998). Ca2+ channel-regulated neuronal gene expression. J Neurobiol 37: 171–189.PubMedGoogle Scholar
  23. Gail A, Brinksmeyer HJ, Eckhorn R (2003). Simultaneous mapping of binocular and monocular receptive fields in awake monkeys for calibrating eye alignment in a dichoptical setup. J Neurosci Methods 126: 41–56.PubMedGoogle Scholar
  24. Gail A, Brinksmeyer HJ, Eckhorn R (2004). Perception-related modulations of local field potential power and coherence in primary visual cortex of awake monkey during binocular rivalry. Cereb Cortex 14: 300–313.PubMedGoogle Scholar
  25. Gattass R, Nascimento-Silva S, Soares JG, Lima B, Jansen AK, Diogo AC, Farias MF, Botelho MM, Mariani OS, Azzi J, Fiorani M (2005). Cortical visual areas in monkeys: location, topography, connections, columns, plasticity and cortical dynamics. Philos Trans R Soc Lond B Biol Sci 360: 709–731.PubMedGoogle Scholar
  26. Ghosh A, Ginty DD, Bading H, Greenberg ME (1994). Calcium regulation of gene expression in neuronal cells. J Neurobiol 25: 294–303.PubMedGoogle Scholar
  27. Ginty DD, Bading H, Greenberg ME (1992). Trans-synaptic regulation of gene expression. Curr Opin Neurobiol 2: 312–316.PubMedGoogle Scholar
  28. Glazewski S, Fox K (1996). Time course of experience-dependent synaptic potentiation and depression in barrel cortex of adolescent rats. J Neurophysiol 75: 1714–1729.PubMedGoogle Scholar
  29. Grutzendler J, Kasthuri N, Gan WB (2002). Long-term dendritic spine stability in the adult cortex. Nature 420: 812–816.PubMedGoogle Scholar
  30. Guzowski JF, Timlin JA, Roysam B, McNaughton BL, Worley PF, Barnes CA (2005). Mapping behaviorally relevant neural circuits with immediate-early gene expression. Curr Opin Neurobiol 15: 599–606.PubMedGoogle Scholar
  31. Herdegen T, Leah JD (1998). Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 28: 370–490.PubMedGoogle Scholar
  32. Hess J, Angel P, Schorpp-Kistner M (2004). AP-1 subunits: quarrel and harmony among siblings. J Cell Sci 117: 5965–5973.PubMedGoogle Scholar
  33. Hollmann M, Heinemann S (1994). Cloned glutamate receptors. Annu Rev Neurosci 17: 31–108.PubMedGoogle Scholar
  34. Horton JC (1984). Cytochrome oxidase patches: a new cytoarchitectonic feature of monkey visual cortex. Philos Trans R Soc Lond B Biol Sci 304: 199–253.PubMedGoogle Scholar
  35. Horton JC, Hedley-Whyte ET (1984). Mapping of cytochrome oxidase patches and ocular dominance columns in human visual cortex. Philos Trans R Soc Lond B Biol Sci 304: 255–272.PubMedGoogle Scholar
  36. Hubel DH, Wiesel TN (1962). Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J Physiol 160: 106–154.PubMedGoogle Scholar
  37. Hubel DH, Wiesel TN (1968). Receptive fields and functional architecture of monkey striate cortex. J Physiol 195: 215–243.PubMedGoogle Scholar
  38. Hubel DH, Wiesel TN (1970). The period of susceptibility to the physiological effects of unilateral eye closure in kittens. J Physiol 206: 419–436.PubMedGoogle Scholar
  39. Hubel DH, Wiesel TN (1972). Laminar and columnar distribution of geniculo-cortical fibers in the macaque monkey. J Comp Neurol 146: 421–450.PubMedGoogle Scholar
  40. Hubel DH, Wiesel TN, LeVay S (1977). Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R Soc Lond B Biol Sci 278: 377–409.PubMedGoogle Scholar
  41. Hughes P, Dragunow M (1995). Induction of immediate-early genes and the control of neurotransmitter-regulated gene expression within the nervous system. Pharmacol Rev 47: 133–178.PubMedGoogle Scholar
  42. Kaczmarek L, Chaudhuri A (1997). Sensory regulation of immediate-early gene expression in mammalian visual cortex: implications for functional mapping and neural plasticity. Brain Res Brain Res Rev 23: 237–256.PubMedGoogle Scholar
  43. Kaczmarek L, Robertson HA (2002). Immediate Early Genes and Inducible Transcription Factors in Mapping of the Central Nervous System Function and Dysfunction. Amsterdam: Elsevier Science B.V.Google Scholar
  44. Kaczmarek L, Zangenehpour S, Chaudhuri A (1999). Sensory regulation of immediate-early genes c-fos and zif268 in monkey visual cortex at birth and throughout the critical period. Cereb Cortex 9: 179–187.PubMedGoogle Scholar
  45. Kaminska B, Kaczmarek L, Chaudhuri A (1996). Visual stimulation regulates the expression of transcription factors and modulates the composition of AP-1 in visual cortex. J Neurosci 16: 3968–3978.PubMedGoogle Scholar
  46. Kaminska B, Pyrzynska B, Ciechomska I, Wisniewska M (2000). Modulation of the composition of AP-1 complex and its impact on transcriptional activity. Acta Neurobiol Exp (Wars) 60: 395–402.Google Scholar
  47. Kaplan IV, Guo Y, Mower GD (1996). Immediate early gene expression in cat visual cortex during and after the critical period: differences between EGR-1 and Fos proteins. Brain Res Mol Brain Res 36: 12–22.PubMedGoogle Scholar
  48. Kobierski LA, Chu HM, Tan Y, Comb MJ (1991). cAMP-dependent regulation of proenkephalin by JunD and JunB: positive and negative effects of AP-1 proteins. Proc Natl Acad Sci USA 88: 10222–10226.PubMedGoogle Scholar
  49. Krubitzer LA, Kaas JH (1990). Cortical connections of MT in four species of primates: areal, modular, and retinotopic patterns. Vis Neurosci 5: 165–204.PubMedGoogle Scholar
  50. Lyford GL, Yamagata K, Kaufmann WE, Barnes CA, Sanders LK, Copeland NG, Gilbert DJ, Jenkins NA, Lanahan AA, Worley PF (1995). Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites. Neuron 14: 433–445.PubMedGoogle Scholar
  51. Mayer ML, Armstrong N (2004). Structure and function of glutamate receptor ion channels. Annu Rev Physiol 66: 161–181.PubMedGoogle Scholar
  52. Milbrandt J (1987). A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science 238: 797–799.PubMedGoogle Scholar
  53. Miyashita Y, Kameyama M, Hasegawa I, Fukushima T (1998). Consolidation of visual associative long-term memory in the temporal cortex of primates. Neurobiol Learn Mem 70:197–211.PubMedGoogle Scholar
  54. Montero V (2005). Attentional activation of cortico-reticulo-thalamic pathways revealed by Fos imaging. In: Plasticity in the Visual System: From Genes to Circuits (Pinaud R, Tremere LA, De Weerd P, eds), pp. 97–124. New York: Springer-Verlag.Google Scholar
  55. Montero VM, Jian S (1995). Induction of c-fos protein by patterned visual stimulation in central visual pathways of the rat. Brain Res 690:189–199.PubMedGoogle Scholar
  56. Morgan JI, Curran T (1991). Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci 14:421–451.PubMedGoogle Scholar
  57. Nedivi E, Fieldust S, Theill LE, Hevron D (1996). A set of genes expressed in response to light in the adult cerebral cortex and regulated during development. Proc Natl Acad Sci USA 93:2048–2053.PubMedGoogle Scholar
  58. Nicolelis MA, Lin RC, Woodward DJ, Chapin JK (1993). Dynamic and distributed properties of manyneuron ensembles in the ventral posterior medial thalamus of awake rats. Proc Natl Acad Sci USA 90:2212–2216.PubMedGoogle Scholar
  59. Nicolelis MA, Dimitrov D, Carmena JM, Crist R, Lehew G, Kralik JD, Wise SP (2003). Chronic, multisite, multielectrode recordings in macaque monkeys. Proc Natl Acad Sci USA 100:11041–11046.PubMedGoogle Scholar
  60. Nimchinsky EA, Sabatini BL, Svoboda K (2002). Structure and function of dendritic spines. Annu Rev Physiol 64:313–353.PubMedGoogle Scholar
  61. Okuno H, Miyashita Y (1996) Expression of the transcription factor Zif268 in the temporal cortex of monkeys during visual paired associate learning. Eur J Neurosci 8:2118–2128.PubMedGoogle Scholar
  62. Okuno H, Kanou S, Tokuyama W, Li YX, Miyashita Y (1997). Layer-specific differential regulation of transcription factors Zif268 and Jun-D in visual cortex V1 and V2 of macaque monkeys. Neuroscience 81:653–666.PubMedGoogle Scholar
  63. Papa M, Pellicano MP, Welzl H, Sadile AG (1993). Distributed changes in c-Fos and c-Jun immunoreactivity in the rat brain associated with arousal and habituation to novelty. Brain Res Bull 32:509–515.PubMedGoogle Scholar
  64. Petersen CC, Sakmann B (2001). Functionally independent columns of rat somatosensory barrel cortex revealed with voltage-sensitive dye imaging. J Neurosci 21:8435–8446.PubMedGoogle Scholar
  65. Petersohn D, Thiel G (1996). Role of zinc-finger proteins Sp1 and zif268/egr-1 in transcriptional regulation of the human synaptobrevin II gene. Eur J Biochem 239:827–834.PubMedGoogle Scholar
  66. Petersohn D, Schoch S, Brinkmann DR, Thiel G (1995). The human synapsin II gene promoter. Possible role for the transcription factor zif268/egr-1, polyoma enhancer activator 3, and AP2. J Biol Chem 270:24361–24369.PubMedGoogle Scholar
  67. Pinaud R (2004). Experience-dependent immediate early gene expression in the adult central nervous system: evidence from enriched-environment studies. Int J Neurosci 114:321–333.PubMedGoogle Scholar
  68. Pinaud R (2005). Critical calcium-regulated biochemical and gene expression programs involved in experience-dependent plasticity. In: Plasticity in the Visual System: From Genes to Circuits (Pinaud R, Tremere LA, De Weerd P, eds), pp. 153–180. New York: Springer-Verlag.Google Scholar
  69. Pinaud R, Tremere LA (2005). Experience-dependent rewiring of retinal circuitry: involvement of immediate early genes. In: Plasticity in the Visual System: From Genes to Circuits (Pinaud R, Tremere LA, De Weerd P, eds), pp. 79–95. New York: Spinger-Verlag.Google Scholar
  70. Pinaud R, Tremere LA, Penner MR (2000). Light-induced zif268 expression is dependent on noradrenergic input in rat visual cortex. Brain Res 882:251–255.PubMedGoogle Scholar
  71. Pinaud R, Penner MR, Robertson HA, Currie RW (2001). Upregulation of the immediate early gene arc in the brains of rats exposed to environmental enrichment: implications for molecular plasticity. Brain Res Mol Brain Res 91:50–56.PubMedGoogle Scholar
  72. Pinaud R, Tremere LA, Penner MR, Hess FF, Robertson HA, Currie RW (2002a). Complexity of sensory environment drives the expression of candidate-plasticity gene, nerve growth factor induced-A. Neuroscience 112:573–582.PubMedGoogle Scholar
  73. Pinaud R, De Weerd P, Currie RW, Fiorani Jr M, Hess FF, Tremere LA (2003a). Ngfi-a immunoreactivity in the primate retina: implications for genetic regulation of plasticity. Int J Neurosci 113:1275–1285.PubMedGoogle Scholar
  74. Pinaud R, Tremere LA, Penner MR, Hess FF, Barnes S, Robertson HA, Currie RW (2002b). Plasticity-driven gene expression in the rat retina. Brain Res Mol Brain Res 98:93–101.PubMedGoogle Scholar
  75. Pinaud R, Vargas CD, Ribeiro S, Monteiro MV, Tremere LA, Vianney P, Delgado P, Mello CV, Rocha-Miranda CE, Volchan E (2003b). Light-induced Egr-1 expression in the striate cortex of the opossum. Brain Res Bull 61:139–146.PubMedGoogle Scholar
  76. Pospelov VA, Pospelova TV, Julien JP (1994). AP-1 and Krox-24 transcription factors activate the neurofilament light gene promoter in P19 embryonal carcinoma cells. Cell Growth Differ 5:187–196.PubMedGoogle Scholar
  77. Prusky GT, Reidel C, Douglas RM (2000). Environmental enrichment from birth enhances visual acuity but not place learning in mice. Behav Brain Res 114:11–15.PubMedGoogle Scholar
  78. Rosen KM, McCormack MA, Villa-Komaroff L, Mower GD (1992). Brief visual experience induces immediate early gene expression in the cat visual cortex. Proc Natl Acad Sci USA 89:5437–5441.PubMedGoogle Scholar
  79. Rosenzweig MR, Bennett EL, Diamond MC (1972). Brain changes in relation to experience. Sci Am 226:22–29.Google Scholar
  80. Sharp FR, Sagar SM, Swanson RA (1993). Metabolic mapping with cellular resolution: c-fos vs. 2-deoxyglucose. Crit Rev Neurobiol 7:205–228.PubMedGoogle Scholar
  81. Silveira LC, de Matos FM, Pontes-Arruda A, Picanco-Diniz CW, Muniz JA (1996). Late development of Zif268 ocular dominance columns in primary visual cortex of primates. Brain Res 732:237–241.PubMedGoogle Scholar
  82. Soares JG, Pereira AC, Botelho EP, Pereira SS, Fiorani M, Gattass R (2005). Differential expression of Zif268 and c-Fos in the primary visual cortex and lateral geniculate nucleus of normal Cebus monkeys and after monocular lesions. J Comp Neurol 482:166–175.PubMedGoogle Scholar
  83. Sokoloff L (1981). Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J Cereb Blood Flow Metab 1:7–36.PubMedGoogle Scholar
  84. Steward O, Worley PF (2001a). A cellular mechanism for targeting newly synthesized mRNAs to synaptic sites on dendrites. Proc Natl Acad Sci USA 98:7062–7068.PubMedGoogle Scholar
  85. Steward O, Worley PF (2001b). Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation. Neuron 30:227–240.PubMedGoogle Scholar
  86. Steward O, Wallace CS, Lyford GL, Worley PF (1998). Synaptic activation causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on dendrites. Neuron 21:741–751.PubMedGoogle Scholar
  87. Thiel G, Schoch S, Petersohn D (1994). Regulation of synapsin I gene expression by the zinc finger transcription factor zif268/egr-1. J Biol Chem 269:15294–15301.PubMedGoogle Scholar
  88. Tieman SB (1985). The anatomy of geniculocortical connections in monocularly deprived cats. Cell Mol Neurobiol 5:35–45.PubMedGoogle Scholar
  89. Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR, Welker E, Svoboda K (2002). Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420:788–794.PubMedGoogle Scholar
  90. van Praag H, Kempermann G, Gage FH (2000). Neural consequences of environmental enrichment. Nat Rev Neurosci 1:191–198.PubMedGoogle Scholar
  91. Volkmar FR, Greenough WT (1972). Rearing complexity affects branching of dendrites in the visual cortex of the rat. Science 176:1145–1147.Google Scholar
  92. Wallace CS, Withers GS, Weiler IJ, George JM, Clayton DF, Greenough WT (1995). Correspondence between sites of NGFI-A induction and sites of morphological plasticity following exposure to environmental complexity. Brain Res Mol Brain Res 32:211–220.PubMedGoogle Scholar
  93. Wiesel TN, Hubel DH (1963). Single-Cell Responses in Striate Cortex of Kittens Deprived of Vision in One Eye. J Neurophysiol 26:1003–1017.PubMedGoogle Scholar
  94. Wong WK, Ou XM, Chen K, Shih JC (2002). Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1. J Biol Chem 277:22222–22230.PubMedGoogle Scholar
  95. Wong-Riley MT (1989). Cytochrome oxidase: an endogenous metabolic marker for neuronal activity. Trends Neurosci 12:94–101.PubMedGoogle Scholar
  96. Worley PF, Christy BA, Nakabeppu Y, Bhat RV, Cole AJ, Baraban JM (1991). Constitutive expression of zif268 in neocortex is regulated by synaptic activity. Proc Natl Acad Sci USA 88:5106–5110.PubMedGoogle Scholar
  97. Wurtz RH (1969). Visual receptive fields of striate cortex neurons in awake monkeys. J Neurophysiol 32:727–742.PubMedGoogle Scholar
  98. Yamada Y, Hada Y, Imamura K, Mataga N, Watanabe Y, Yamamoto M (1999). Differential expression of immediate-early genes, c-fos and zif268, in the visual cortex of young rats: effects of a noradrenergic neurotoxin on their expression. Neuroscience 92:473–484.PubMedGoogle Scholar
  99. Zhang F, Vanduffel W, Schiffmann SN, Mailleux P, Arckens L, Vandesande F, Orban GA, Vanderhaeghen JJ (1995). Decrease of zif-268 and c-fos and increase of c-jun mRNA in the cat areas 17, 18 and 19 following complete visual deafferentation. Eur J Neurosci 7:1292–1296.PubMedGoogle Scholar
  100. Zhang F, Halleux P, Arckens L, Vanduffel W, Van Bree L, Mailleux P, Vandesande F, Orban GA, Vanderhaeghen JJ (1994). Distribution of immediate early gene zif-268, c-fos, c-jun and jun-D mRNAs in the adult cat with special references to brain region related to vision. Neurosci Lett 176:137–141.PubMedGoogle Scholar
  101. Zhu XO, Brown MW, McCabe BJ, Aggleton JP (1995). Effects of the novelty or familiarity of visual stimuli on the expression of the immediate early gene c-fos in rat brain. Neuroscience 69:821–829.PubMedGoogle Scholar

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© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Raphael Pinaud
    • 1
  • Thomas A. Terleph
    • 2
  • R. William Currie
    • 3
  • Liisa A. Tremere
    • 1
  1. 1.Department of NeurobiologyDuke University Medical CenterDurhamUSA
  2. 2.Department of BiologySacred Heart UniversityFairfieldUSA
  3. 3.Department of Anatomy and NeurobiologyDalhousie UniversityHalifaxCanada

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