Table of Contents Author Guidelines Submit a Manuscript
Neural Plasticity
Volume 2013, Article ID 318596, 24 pages
http://dx.doi.org/10.1155/2013/318596
Review Article

Immature Dentate Gyrus: An Endophenotype of Neuropsychiatric Disorders

1Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
2CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
3Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, 5-1 Aza-Higashiyama, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan
4CNS, Astellas Research Institute of America LLC, 8045 Lamon Avenue, Skokie, IL 60077, USA

Received 5 March 2013; Revised 17 April 2013; Accepted 19 April 2013

Academic Editor: Chitra D. Mandyam

Copyright © 2013 Hideo Hagihara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. Yamasaki, M. Maekawa, K. Kobayashi et al., “Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders,” Molecular Brain, vol. 1, article 6, 2008. View at Google Scholar · View at Scopus
  2. K. Takao, K. Kobayashi, H. Hagihara et al., “Deficiency of Schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia,” Neuropsychopharmacology, 2013. View at Publisher · View at Google Scholar
  3. K. Ohira, K. Kobayashi, K. Toyama et al., “Synaptosomal-associated protein 25 mutation converts dentate granule cells to an immature state in adult mice,” Molecular Brain, vol. 6, article 12, 2013. View at Google Scholar
  4. H. Hagihara, H. K. Nakamura, K. Toyama, I. A. Graef, G. R. Crabtree, and T. Miyakawa, “Forebrain-specific calcineurin deficiency causes immaturity of the dentate granule cells in adult mice,” SfN meeting 2011 abstract.
  5. K. Kobayashi, Y. Ikeda, A. Sakai et al., “Reversal of hippocampal neuronal maturation by serotonergic antidepressants,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 18, pp. 8434–8439, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. R. Shin, K. Kobayashi, H. Hagihara et al., “The immature dentate gyrus represents a common endophenotype of psychiatric disorders and epilepsy,” Bipolar Disorders, 2013. View at Publisher · View at Google Scholar
  7. N. M. Walton, Y. Zhou, J. H. Kogan et al., “Detection of an immature dentate gyrus feature in human schizophrenia/bipolar patients,” Translational Psychiatry, vol. 2, no. 7, article e135, 2012. View at Google Scholar
  8. K. Takao, N. Yamasaki, and T. Miyakawa, “Impact of brain-behavior phenotypying of genetically-engineered mice on research of neuropsychiatric disorders,” Neuroscience Research, vol. 58, no. 2, pp. 124–132, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. D. J. Gerber, D. Hall, T. Miyakawa et al., “Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 15, pp. 8993–8998, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Miyakawa, L. M. Leiter, D. J. Gerber et al., “Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 15, pp. 8987–8992, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. D. G. Winder and J. D. Sweatt, “Roles of serine/threonine phosphatases in hippocampal synaptic plasticity,” Nature Reviews Neuroscience, vol. 2, no. 7, pp. 461–474, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Shoji, H. Hagihara, K. Takao, S. Hattori, and T. Miyakawa, “T-maze forced alternation and left-right discrimination tasks for assessing working and reference memory in mice,” Journal of Visualized Experiments, no. 60, article e3300, 2012. View at Publisher · View at Google Scholar
  13. N. Matsuo, N. Yamasaki, K. Ohira et al., “Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice,” Frontiers in Behavioral Neuroscience, vol. 3, article 20, 2009. View at Google Scholar
  14. C. E. Young, K. Arima, J. Xie et al., “SNAP-25 deficit and hippocampal connectivity in schizophrenia,” Cerebral Cortex, vol. 8, no. 3, pp. 261–268, 1998. View at Publisher · View at Google Scholar · View at Scopus
  15. C. M. Lewis, D. F. Levinson, L. H. Wise et al., “Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia,” American Journal of Human Genetics, vol. 73, no. 1, pp. 34–48, 2003. View at Google Scholar
  16. C. L. Barr, Y. Feng, K. Wigg et al., “Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder,” Molecular Psychiatry, vol. 5, no. 4, pp. 405–409, 2000. View at Google Scholar · View at Scopus
  17. T. K. Choi, H. S. Lee, J. W. Kim et al., “Support for the MnlI polymorphism of SNAP25; a Korean ADHD case-control study,” Molecular Psychiatry, vol. 12, no. 3, pp. 224–226, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Zhang, A. P. Vilaythong, D. Yoshor, and J. L. Noebels, “Elevated thalamic low-voltage-activated currents precede the onset of absence epilepsy in the SNAP25-deficient mouse mutant Coloboma,” The Journal of Neuroscience, vol. 24, no. 22, pp. 5239–5248, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Kataoka, R. Kuwahara, R. Matsuo, M. Sekiguchi, K. Inokuchi, and M. Takahashi, “Development- and activity-dependent regulation of SNAP-25 phosphorylation in rat brain,” Neuroscience Letters, vol. 407, no. 3, pp. 258–262, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Horiuchi, H. Ishiguro, M. Koga et al., “Support for association of the PPP3CC gene with schizophrenia,” Molecular Psychiatry, vol. 12, no. 10, pp. 891–893, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. H. Zeng, S. Chattarji, M. Barbarosie et al., “Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory,” Cell, vol. 107, no. 5, pp. 617–629, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Hagihara, K. Toyama, N. Yamasaki, and T. Miyakawa, “Dissection of hippocampal dentate gyrus from adult mouse,” Journal of Visualized Experiments, no. 33, 2009. View at Publisher · View at Google Scholar
  23. L. M. Valor, D. Jancic, R. Lujan, and A. Barco, “Ultrastructural and transcriptional profiling of neuropathological misregulation of CREB function,” Cell Death & Differentiation, vol. 17, no. 10, pp. 1636–1644, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. K. Merz, S. Herold, and D. C. Lie, “CREB in adult neurogenesis—master and partner in the development of adult-born neurons?” The European Journal of Neuroscience, vol. 33, no. 6, pp. 1078–1086, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Ohira and T. Miyakawa, “Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice,” Molecular Brain, vol. 4, no. 1, article 10, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. S. C. Dulawa, K. A. Holick, B. Gundersen, and R. Hen, “Effects of chronic fluoxetine in animal models of anxiety and depression,” Neuropsychopharmacology, vol. 29, no. 7, pp. 1321–1330, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. R. Alonso, G. Griebel, G. Pavone, J. Stemmelin, G. Le Fur, and P. Soubrié, “Blockade of CRF1 or V1B receptors reverses stress-induced suppression of neurogenesis in a mouse model of depression,” Molecular Psychiatry, vol. 9, no. 3, 224 pages, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. D. J. David, B. A. Samuels, Q. Rainer et al., “Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression,” Neuron, vol. 62, no. 4, pp. 479–493, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Kobayashi, Y. Ikeda, and H. Suzuki, “Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine,” Molecular Brain, vol. 4, no. 1, article 12, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Detour, H. Schroeder, D. Desor, and A. Nehlig, “A 5-month period of epilepsy impairs spatial memory, decreases anxiety, but spares object recognition in the lithium-pilocarpine model in adult rats,” Epilepsia, vol. 46, no. 4, pp. 499–508, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. I. Sillaber, M. Panhuysen, M. S. H. Henniger et al., “Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine,” Psychopharmacology, vol. 200, no. 4, pp. 557–572, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. H. Hagihara, K. Ohira, K. Toyama, and T. Miyakawa, “Expression of the AMPA receptor subunits GluR1 and GluR2 is associated with granule cell maturation in the dentate gyrus,” Frontiers in Neurogenesis, vol. 5, article 100, 2011. View at Google Scholar
  33. H. Hagihara, M. Hara, K. Tsunekawa, Y. Nakagawa, M. Sawada, and K. Nakano, “Tonic-clonic seizures induce division of neuronal progenitor cells with concomitant changes in expression of neurotrophic factors in the brain of pilocarpine-treated mice,” Molecular Brain Research, vol. 139, no. 2, pp. 258–266, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. O. K. Okamoto, L. Janjoppi, F. M. Bonone et al., “Whole transcriptome analysis of the hippocampus: toward a molecular portrait of epileptogenesis,” BMC Genomics, vol. 11, no. 1, article 230, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. B. H. Cha, C. Akman, D. C. Silveira, X. Liu, and G. L. Holmes, “Spontaneous recurrent seizure following status epilepticus enhances dentate gyrus neurogenesis,” Brain and Development, vol. 26, no. 6, pp. 394–397, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. N. N. Karpova, A. Pickenhagen, J. Lindholm et al., “Fear erasure in mice requires synergy between antidepressant drugs and extinction training,” Science, vol. 334, no. 6063, pp. 1731–1734, 2011. View at Google Scholar
  37. T. K. Hensch, “Critical period plasticity in local cortical circuits,” Nature Reviews Neuroscience, vol. 6, no. 11, pp. 877–888, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. S. Berretta, “Extracellular matrix abnormalities in schizophrenia,” Neuropharmacology, vol. 62, no. 3, pp. 1584–1597, 2012. View at Google Scholar
  39. T. Pizzorusso, P. Medini, N. Berardi, S. Chierzi, J. W. Fawcett, and L. Maffei, “Reactivation of ocular dominance plasticity in the adult visual cortex,” Science, vol. 298, no. 5596, pp. 1248–1251, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. N. Gogolla, P. Caroni, A. Lüthi, and C. Herry, “Perineuronal nets protect fear memories from erasure,” Science, vol. 325, no. 5945, pp. 1258–1261, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. J. F. M. Vetencourt, A. Sale, A. Viegi et al., “The antidepressant fluoxetine restores plasticity in the adult visual cortex,” Science, vol. 320, no. 5874, pp. 385–388, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. E. S. Lein, M. J. Hawrylycz, N. Ao et al., “Genome-wide atlas of gene expression in the adult mouse brain,” Nature, vol. 445, no. 7124, pp. 168–176, 2007. View at Google Scholar
  43. C. A. Altar, L. W. Jurata, V. Charles et al., “Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts,” Biological Psychiatry, vol. 58, no. 2, pp. 85–96, 2005. View at Publisher · View at Google Scholar · View at Scopus
  44. T. M. Hyde, B. K. Lipska, T. Ali et al., “Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia,” The Journal of Neuroscience, vol. 31, no. 30, pp. 11088–11095, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. P. Blaesse, M. S. Airaksinen, C. Rivera, and K. Kaila, “Cation-chloride cotransporters and neuronal function,” Neuron, vol. 61, no. 6, pp. 820–838, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. D. A. Lewis, D. A. Cruz, D. S. Melchitzky, and J. N. Pierri, “Lamina-specific deficits in parvalbumin-immunoreactive varicosities in the prefrontal cortex of subjects with schizophrenia: evidence for fewer projections from the thalamus,” The American Journal of Psychiatry, vol. 158, no. 9, pp. 1411–1422, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. G. P. Reynolds, Z. J. Zhang, and C. L. Beasley, “Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immunoreactivity,” Brain Research Bulletin, vol. 55, no. 5, pp. 579–584, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. C. L. Beasley, Z. J. Zhang, I. Patten, and G. P. Reynolds, “Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins,” Biological Psychiatry, vol. 52, no. 7, pp. 708–715, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. C. L. Beasley and G. P. Reynolds, “Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics,” Schizophrenia Research, vol. 24, no. 3, pp. 349–355, 1997. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Y. Wang, K. M. Lohmann, C. K. Yang et al., “Bipolar disorder type 1 and schizophrenia are accompanied by decreased density of parvalbumin- and somatostatin-positive interneurons in the parahippocampal region,” Acta Neuropathologica, vol. 122, no. 5, pp. 615–626, 2011. View at Google Scholar
  51. B. W. Okaty, M. N. Miller, K. Sugino, C. M. Hempel, and S. B. Nelson, “Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons,” The Journal of Neuroscience, vol. 29, no. 21, pp. 7040–7052, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. M. J. Gandal, A. M. Nesbitt, R. M. McCurdy, and M. D. Alter, “Measuring the maturity of the fast-spiking interneuron transcriptional program in autism, schizophrenia, and bipolar disorder,” PLoS ONE, vol. 7, no. 8, Article ID e41215, 2012. View at Google Scholar
  53. H. Pantazopoulos, T. U. W. Woo, M. P. Lim, N. Lange, and S. Berretta, “Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia,” Archives of General Psychiatry, vol. 67, no. 2, pp. 155–166, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. H. Pantazopoulos, N. Lange, R. J. Baldessarini, and S. Berretta, “Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar disorder or schizophrenia,” Biological Psychiatry, vol. 61, no. 5, pp. 640–652, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Fukuda, Y. Yamasaki, T. Iwaki et al., “Characterization of the biological functions of a transcription factor, c-myc intron binding protein 1 (MIBP1),” Journal of Biochemistry, vol. 131, no. 3, pp. 349–357, 2002. View at Google Scholar · View at Scopus
  56. S. M. Purcell, N. R. Wray, J. L. Stone et al., “Common polygenic variation contributes to risk of schizophrenia and bipolar disorder,” Nature, vol. 460, no. 7256, pp. 748–752, 2009. View at Google Scholar
  57. J. Shi, D. F. Levinson, J. Duan et al., “Common variants on chromosome 6p22. 1 are associated with schizophrenia,” Nature, vol. 460, no. 7256, pp. 753–757, 2009. View at Google Scholar
  58. Y. Shi, Z. Li, Q. Xu et al., “Common variants on 8p12 and 1q24. 2 confer risk of schizophrenia,” Nature Genetics, vol. 43, no. 12, pp. 1224–1227, 2011. View at Google Scholar
  59. H. Stefansson, R. A. Ophoff, S. Steinberg et al., “Common variants conferring risk of schizophrenia,” Nature, vol. 460, no. 7256, pp. 744–747, 2009. View at Google Scholar
  60. W. H. Yue, H.-F. Wang, L. D. Sun et al., “Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11. 2,” Nature Genetics, vol. 43, no. 12, pp. 1228–1231, 2011. View at Google Scholar
  61. P. J. van den Elsen, S. J. P. Gobin, M. C. J. A. van Eggermond, and A. Peijnenburg, “Regulation of MHC class I and II gene transcription: differences and similarities,” Immunogenetics, vol. 48, no. 3, pp. 208–221, 1998. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Y. Kimura, H. Hosokawa, M. Yamashita et al., “Regulation of T helper type 2 cell differentiation by murine Schnurri-2,” Journal of Experimental Medicine, vol. 201, no. 3, pp. 397–408, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Y. Kimura, C. Iwamura, A. Suzuki et al., “Schnurri-2 controls memory Th1 and Th2 cell numbers in vivo,” Journal of Immunology, vol. 178, no. 8, pp. 4926–4936, 2007. View at Google Scholar
  64. N. Muller and M. Schwarz, “Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission,” Neurotoxicity Research, vol. 10, no. 2, pp. 131–148, 2006. View at Google Scholar
  65. B. H. Miller, L. E. Schultz, A. Gulati, M. D. Cameron, and M. T. Pletcher, “Genetic regulation of behavioral and neuronal responses to fluoxetine,” Neuropsychopharmacology, vol. 33, no. 6, pp. 1312–1322, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. M. Kataoka, S. Yamamori, E. Suzuki et al., “A single amino acid mutation in SNAP-25 induces anxiety-related behavior in mouse,” PLoS ONE, vol. 6, no. 9, Article ID e25158, 2011. View at Google Scholar
  67. S. Otsuka, S. Yamamori, S. Watanabe et al., “PKC-dependent phosphorylation of SNAP-25 plays a crucial role in the suppression of epileptogenesis and anxiety-related behavior in postnatal period of mouse,” Neuroscience Research, vol. 71, supplement, article e296, 2011. View at Google Scholar
  68. A. Vezzani, “Inflammation and epilepsy,” Epilepsy Currents, vol. 5, no. 1, pp. 1–6, 2005. View at Google Scholar
  69. A. Vezzani and T. Granata, “Brain inflammation in epilepsy: experimental and clinical evidence,” Epilepsia, vol. 46, no. 11, pp. 1724–1743, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. O. Tomkins, O. Friedman, S. Ivens et al., “Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex,” Neurobiology of Disease, vol. 25, no. 2, pp. 367–377, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. E. A. van Vliet, S. da C. Araújo, S. Redeker, R. Van Schaik, E. Aronica, and J. A. Gorter, “Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy,” Brain, vol. 130, no. 2, pp. 521–534, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. L. Uva, L. Librizzi, N. Marchi et al., “Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeability,” Neuroscience, vol. 151, no. 1, pp. 303–312, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. P. F. Fabene, G. N. Mora, M. Martinello et al., “A role for leukocyte-endothelial adhesion mechanisms in epilepsy,” Nature Medicine, vol. 14, no. 12, pp. 1377–1383, 2008. View at Google Scholar
  74. M. Zhou, W. Li, S. Huang et al., “mTOR inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons,” Neuron, vol. 77, no. 4, pp. 647–654, 2013. View at Google Scholar
  75. D. St Clair, D. Blackwood, W. Muir et al., “Association within a family of a balanced autosomal translocation with major mental illness,” The Lancet, vol. 336, no. 8706, pp. 13–16, 1990. View at Publisher · View at Google Scholar · View at Scopus
  76. N. Burnashev, H. Monyer, P. H. Seeburg, and B. Sakmann, “Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit,” Neuron, vol. 8, no. 1, pp. 189–198, 1992. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Hollmann, M. Hartley, and S. Heinemann, “Ca2+ permeability of KA-AMPA-gated glutamate receptor channels depends on subunit composition,” Science, vol. 252, no. 5007, pp. 851–853, 1991. View at Google Scholar · View at Scopus
  78. R. I. Hume, R. Dingledine, and S. F. Heinemann, “Identification of a site in glutamate receptor subunits that controls calcium permeability,” Science, vol. 253, no. 5023, pp. 1028–1031, 1991. View at Google Scholar · View at Scopus
  79. C. Zhao, W. Deng, and F. H. Gage, “Mechanisms and functional implications of adult neurogenesis,” Cell, vol. 132, no. 4, pp. 645–660, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Jessberger and G. Kempermann, “Adult-born hippocampal neurons mature into activity-dependent responsiveness,” The European Journal of Neuroscience, vol. 18, no. 10, pp. 2707–2712, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. P. S. Goldman-Rakic, “Working memory dysfunction in schizophrenia,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 6, no. 4, pp. 348–357, 1994. View at Google Scholar · View at Scopus
  82. B. Elvevåg and T. E. Goldberg, “Cognitive impairment in schizophrenia is the core of the disorder,” Critical Reviews in Neurobiology, vol. 14, no. 1, pp. 1–21, 2000. View at Google Scholar
  83. D. L. Braff and M. A. Geyer, “Sensorimotor gating and schizophrenia: human and animal model studies,” Archives of General Psychiatry, vol. 47, no. 2, pp. 181–188, 1990. View at Google Scholar · View at Scopus
  84. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association, Washington, DC, USA, 4th edition, 1994.
  85. R. R. Gainetdinov, A. R. Mohn, L. M. Bohn, and M. G. Caron, “Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 20, pp. 11047–11054, 2001. View at Publisher · View at Google Scholar · View at Scopus
  86. P. R. Maycox, F. Kelly, A. Taylor et al., “Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function,” Molecular Psychiatry, vol. 14, no. 12, pp. 1083–1094, 2009. View at Google Scholar
  87. Z. J. Zhang and G. P. Reynolds, “A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia,” Schizophrenia Research, vol. 55, no. 1-2, pp. 1–10, 2002. View at Publisher · View at Google Scholar · View at Scopus
  88. M. B. Knable, B. M. Barci, M. J. Webster, J. Meador-Woodruff, and E. F. Torrey, “Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium,” Molecular Psychiatry, vol. 9, no. 6, pp. 609–620, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. F. M. Benes, B. Lim, D. Matzilevich, J. P. Walsh, S. Subburaju, and M. Minns, “Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 24, pp. 10164–10169, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. J. N. Pierri, A. S. Chaudry, T. U. W. Woo, and D. A. Lewis, “Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects,” The American Journal of Psychiatry, vol. 156, no. 11, pp. 1709–1719, 1999. View at Google Scholar · View at Scopus
  91. J. Gallinat, G. Winterer, C. S. Herrmann, and D. Senkowski, “Reduced oscillatory gamma-band responses in unmedicated schizophrenic patients indicate impaired frontal network processing,” Clinical Neurophysiology, vol. 115, no. 8, pp. 1863–1874, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. L. V. Moran and L. E. Hong, “High vs low frequency neural oscillations in schizophrenia,” Schizophrenia Bulletin, vol. 37, no. 4, pp. 659–663, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. S. R. Sponheim, B. A. Clementz, W. G. Iacono, and M. Beiser, “Resting EEG in first-episode and chronic schizophrenia,” Psychophysiology, vol. 31, no. 1, pp. 37–43, 1994. View at Google Scholar · View at Scopus
  94. A. Abi-Dargham, “Do we still believe in the dopamine hypothesis? New data bring new evidence,” The International Journal of Neuropsychopharmacology, vol. 7, supplement 1, pp. S1–S5, 2004. View at Google Scholar · View at Scopus
  95. G. Winterer and D. R. Weinberger, “Genes, dopamine and cortical signal-to-noise ratio in schizophrenia,” Trends in Neuroscience, vol. 27, no. 11, pp. 683–690, 2004. View at Google Scholar
  96. D. A. Cousins, K. Butts, and A. H. Young, “The role of dopamine in bipolar disorder,” Bipolar Disorders, vol. 11, no. 8, pp. 787–806, 2009. View at Google Scholar
  97. G. Novak and P. Seeman, “Hyperactive mice show elevated D2High receptors, a model for schizophrenia: calcium/calmodulin-dependent kinase II alpha knockouts,” Synapse, vol. 64, no. 10, pp. 794–800, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. C. R. Maxwell, S. J. Kanes, T. Abel, and S. J. Siegel, “Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications,” Neuroscience, vol. 129, no. 1, pp. 101–107, 2004. View at Publisher · View at Google Scholar · View at Scopus
  99. S. J. Kanes, J. Tokarczyk, S. J. Siegel, W. Bilker, T. Abel, and M. P. Kelly, “Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity,” Neuroscience, vol. 144, no. 1, pp. 239–246, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Lisman, H. Schulman, and H. Cline, “The molecular basis of CaMKII function in synaptic and behavioural memory,” Nature Reviews Neuroscience, vol. 3, no. 3, pp. 175–190, 2002. View at Publisher · View at Google Scholar · View at Scopus
  101. D. R. Weinberger, “Implications of normal brain development for the pathogenesis of schizophrenia,” Archives of General Psychiatry, vol. 44, no. 7, pp. 660–669, 1987. View at Google Scholar · View at Scopus
  102. D. R. Weinberger and R. K. McClure, “Neurotoxicity, neuroplasticity, and magnetic resonance imaging morphometry: what is happening in the schizophrenic brain?” Archives of General Psychiatry, vol. 59, no. 6, pp. 553–558, 2002. View at Google Scholar · View at Scopus
  103. S. Marenco and D. R. Weinberger, “The neurodevelopmental hypothesis of schizophrenia: following a trail of evidence from cradle to grave,” Development and Psychopathology, vol. 12, no. 3, pp. 501–527, 2000. View at Google Scholar · View at Scopus
  104. T. D. Cannon, I. M. Rosso, C. E. Bearden, L. E. Sanchez, and T. Hadley, “A prospective cohort study of neurodevelopmental processes in the genesis and epigenesis of schizophrenia,” Development and Psychopathology, vol. 11, no. 3, pp. 467–485, 1999. View at Google Scholar · View at Scopus
  105. B. K. Lipska, “Using animal models to test a neurodevelopmental hypothesis of schizophrenia,” Journal of Psychiatry and Neuroscience, vol. 29, no. 4, pp. 282–286, 2004. View at Google Scholar · View at Scopus
  106. C. T. Ekdahl, J.-H. Claasen, S. Bonde, Z. Kokaia, and O. Lindvall, “Inflammation is detrimental for neurogenesis in adult brain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 23, pp. 13632–13637, 2003. View at Publisher · View at Google Scholar · View at Scopus
  107. S. Das and A. Basu, “Inflammation: a new candidate in modulating adult neurogenesis,” Journal of Neuroscience Research, vol. 86, no. 6, pp. 1199–1208, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. R. L. Hunter, N. Dragicevic, K. Seifert et al., “Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system,” Journal of Neurochemistry, vol. 100, no. 5, pp. 1375–1386, 2007. View at Publisher · View at Google Scholar · View at Scopus
  109. M. T. Fischer, R. Sharma, J. L. Lim et al., “NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury,” Brain, vol. 135, no. 3, pp. 886–899, 2012. View at Google Scholar
  110. Y. Pang, Z. Cai, and P. G. Rhodes, “Disturbance of oligodendrocyte development, hypomyelination and white matter injury in the neonatal rat brain after intracerebral injection of lipopolysaccharide,” Developmental Brain Research, vol. 140, no. 2, pp. 205–214, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. W. Bruck, R. Pfortner, T. Pham et al., “Reduced astrocytic NF-κB activation by laquinimod protects from cuprizone-induced demyelination,” Acta Neuropathologica, vol. 124, no. 3, pp. 411–424, 2012. View at Google Scholar
  112. A. Reif, S. Fritzen, M. Finger et al., “Neural stem cell proliferation is decreased in schizophrenia, but not in depression,” Molecular Psychiatry, vol. 11, no. 5, pp. 514–522, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. M. S. Keshavan, H. A. Nasrallah, and R. Tandon, “Schizophrenia, “Just the Facts” 6. Moving ahead with the schizophrenia concept: from the elephant to the mouse,” Schizophrenia Research, vol. 127, no. 1–3, pp. 3–13, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. H. Nawa and N. Takei, “Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines,” Neuroscience Research, vol. 56, no. 1, pp. 2–13, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. P. H. Patterson, “Immune involvement in schizophrenia and autism: etiology, pathology and animal models,” Behavioural Brain Research, vol. 204, no. 2, pp. 313–321, 2009. View at Publisher · View at Google Scholar · View at Scopus
  116. A. S. Brown and P. H. Patterson, “Maternal infection and schizophrenia: implications for prevention,” Schizophrenia Bulletin, vol. 37, no. 2, pp. 284–290, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. E. Y. Hsiao, S. W. McBride, J. Chow, S. K. Mazmanian, and P. H. Patterson, “Modeling an autism risk factor in mice leads to permanent immune dysregulation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 31, pp. 12776–12781, 2012. View at Google Scholar
  118. P. H. Patterson, “Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness,” Current Opinion in Neurobiology, vol. 12, no. 1, pp. 115–118, 2002. View at Publisher · View at Google Scholar · View at Scopus
  119. L. Shi, S. H. Fatemi, R. W. Sidwell, and P. H. Patterson, “Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring,” The Journal of Neuroscience, vol. 23, no. 1, pp. 297–302, 2003. View at Google Scholar · View at Scopus
  120. J. P. A. Ioannidis, E. E. Ntzani, T. A. Trikalinos, and D. G. Contopoulos-Ioannidis, “Replication validity of genetic association studies,” Nature Genetics, vol. 29, no. 3, pp. 306–309, 2001. View at Publisher · View at Google Scholar · View at Scopus
  121. M. Ayalew, H. Le-Niculescu, D. F. Levey et al., “Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction,” Molecular Psychiatry, vol. 17, no. 9, pp. 887–905, 2012. View at Google Scholar
  122. K. V. Chowdari, K. Mirnics, P. Semwal et al., “Association and linkage analyses of RGS4 polymorphisms in schizophrenia,” Human Molecular Genetics, vol. 11, no. 12, pp. 1373–1380, 2002. View at Google Scholar
  123. K. Mirnics, F. A. Middleton, G. D. Stanwood, D. A. Lewis, and P. Levitt, “Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia,” Molecular Psychiatry, vol. 6, no. 3, pp. 293–301, 2001. View at Publisher · View at Google Scholar · View at Scopus
  124. T. L. Petryshen, F. A. Middleton, A. R. Tahl et al., “Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia,” Molecular Psychiatry, vol. 10, no. 12, pp. 1074–1088, 2005. View at Google Scholar
  125. N. C. Allen, S. Bagade, M. B. McQueen et al., “Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database,” Nature Genetics, vol. 40, no. 7, pp. 827–834, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. S. J. Huffaker, J. Chen, K. K. Nicodemus et al., “A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia,” Nature Medicine, vol. 15, no. 5, pp. 509–518, 2009. View at Publisher · View at Google Scholar · View at Scopus
  127. R. Zakharyan, A. Khoyetsyan, A. Arakelyan et al., “Association of C1QB gene polymorphism with schizophrenia in Armenian population,” BMC Medical Genetics, vol. 12, article 126, 2011. View at Google Scholar
  128. J. Ekelund, D. Lichtermann, I. Hovatta et al., “Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22,” Human Molecular Genetics, vol. 9, no. 7, pp. 1049–1057, 2000. View at Google Scholar · View at Scopus
  129. W. Yan, X.-Y. Guan, E. D. Green et al., “Childhood-onset schizophrenia/autistic disorder and t(1;7) reciprocal translocation: identification of a BAC contig spanning the translocation breakpoint at 7q21,” American Journal of Medical Genetics, vol. 96, no. 6, pp. 749–753, 2000. View at Google Scholar · View at Scopus
  130. M. Bradford, M. H. Law, A. D. Stewart, D. J. Shaw, I. L. Megson, and J. Wei, “The TGM2 gene is associated with schizophrenia in a british population,” American Journal of Medical Genetics B, vol. 150, no. 3, pp. 335–340, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. S. W. Flynn, D. J. Lang, A. L. Mackay et al., “Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins,” Molecular Psychiatry, vol. 8, no. 9, pp. 811–820, 2003. View at Publisher · View at Google Scholar · View at Scopus
  132. K. Iwamoto, M. Bundo, and T. Kato, “Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis,” Human Molecular Genetics, vol. 14, no. 2, pp. 241–253, 2005. View at Publisher · View at Google Scholar · View at Scopus
  133. D. S. Olton and B. C. Papas, “Spatial memory and hippocampal function,” Neuropsychologia, vol. 17, no. 6, pp. 669–682, 1979. View at Publisher · View at Google Scholar · View at Scopus
  134. P. S. Goldman-Rakic, “Regional and cellular fractionation of working memory,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 24, pp. 13473–13480, 1996. View at Publisher · View at Google Scholar · View at Scopus
  135. R. L. McLamb, W. R. Mundy, and H. A. Tilson, “Intradentate colchicine disrupts the acquisition and performance of a working memory task in the radial arm maze,” NeuroToxicology, vol. 9, no. 3, pp. 521–528, 1988. View at Google Scholar · View at Scopus
  136. D. F. Emerich and T. J. Walsh, “Selective working memory impairments following intradentate injection of colchicine: attenuation of the behavioral but not the neuropathological effects by gangliosides GM1 and AGF2,” Physiology & Behavior, vol. 45, no. 1, pp. 93–101, 1989. View at Google Scholar · View at Scopus
  137. A. M. Morris, J. C. Churchwell, R. P. Kesner, and P. E. Gilbert, “Selective lesions of the dentate gyrus produce disruptions in place learning for adjacent spatial locations,” Neurobiology of Learning and Memory, vol. 97, no. 3, pp. 326–331, 2012. View at Google Scholar
  138. R. P. Kesner, “Behavioral functions of the CA3 subregion of the hippocampus,” Learning and Memory, vol. 14, no. 11, pp. 771–781, 2007. View at Publisher · View at Google Scholar · View at Scopus
  139. M. L. Shapiro and D. S. Olton, Memory Systems 1994, MIT Press, 1994.
  140. J. B. Aimone, J. Wiles, and F. H. Gage, “Potential role for adult neurogenesis in the encoding of time in new memories,” Nature Neuroscience, vol. 9, no. 6, pp. 723–727, 2006. View at Publisher · View at Google Scholar · View at Scopus
  141. M. A. Yassa and C. E. L. Stark, “Pattern separation in the hippocampus,” Trends in Neurosciences, vol. 34, no. 10, pp. 515–525, 2011. View at Google Scholar
  142. D. Marr, “Simple memory: a theory for archicortex,” Philosophical Transactions of the Royal Society of London B, vol. 262, no. 841, pp. 23–81, 1971. View at Google Scholar · View at Scopus
  143. B. L. McNaughton and R. G. M. Morris, “Hippocampal synaptic enhancement and information storage within a distributed memory system,” Trends in Neurosciences, vol. 10, no. 10, pp. 408–415, 1987. View at Google Scholar · View at Scopus
  144. R. C. O'Reilly and J. L. McClelland, “Hippocampal conjunctive encoding, storage, and recall: avoiding a trade-off,” Hippocampus, vol. 4, no. 6, pp. 661–682, 1994. View at Publisher · View at Google Scholar · View at Scopus
  145. A. Treves, A. Tashiro, M. E. Witter, and E. I. Moser, “What is the mammalian dentate gyrus good for?” Neuroscience, vol. 154, no. 4, pp. 1155–1172, 2008. View at Publisher · View at Google Scholar · View at Scopus
  146. P. E. Gilbert, R. P. Kesner, and I. Lee, “Dissociating hippocampal subregions: a double dissociation between dentate gyrus and CA1,” Hippocampus, vol. 11, no. 6, pp. 626–636, 2001. View at Publisher · View at Google Scholar · View at Scopus
  147. P. E. Gilbert and R. P. Kesner, “Localization of function within the dorsal hippocampus: the role of the CA3 subregion in paired-associate learning,” Behavioral Neuroscience, vol. 117, no. 6, pp. 1385–1394, 2003. View at Publisher · View at Google Scholar · View at Scopus
  148. I. Lee and R. P. Kesner, “Different contributions of dorsal hippocampal subregios to emory acquisation and retrieval in contextual fear-conditioning,” Hippocampus, vol. 14, no. 3, pp. 301–310, 2004. View at Publisher · View at Google Scholar · View at Scopus
  149. I. Lee and R. P. Kesner, “Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus,” Hippocampus, vol. 14, no. 1, pp. 66–76, 2004. View at Publisher · View at Google Scholar · View at Scopus
  150. J. K. Leutgeb, S. Leutgeb, M.-B. Moser, and E. I. Moser, “Pattern separation in the dentate gyrus and CA3 of the hippocampus,” Science, vol. 315, no. 5814, pp. 961–966, 2007. View at Publisher · View at Google Scholar · View at Scopus
  151. T. J. McHugh, M. W. Jones, J. J. Quinn et al., “Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network,” Science, vol. 317, no. 5834, pp. 94–99, 2007. View at Publisher · View at Google Scholar · View at Scopus
  152. J. B. Aimone, W. Deng, and F. H. Gage, “Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation,” Neuron, vol. 70, no. 4, pp. 589–596, 2011. View at Publisher · View at Google Scholar · View at Scopus
  153. A. Marín-Burgin, L. A. Mongiat, M. B. Pardi, and A. F. Schinder, “Unique processing during a period of high excitation/inhibition balance in adult-born neurons,” Science, vol. 335, no. 6073, pp. 1238–1242, 2012. View at Google Scholar
  154. T. Nakashiba, J. D. Cushman, K. A. Pelkey et al., “Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion,” Cell, vol. 149, no. 1, pp. 188–201, 2012. View at Google Scholar
  155. W. A. M. Swinkels, J. Kuyk, R. van Dyck, and P. Spinhoven, “Psychiatric comorbidity in epilepsy,” Epilepsy and Behavior, vol. 7, no. 1, pp. 37–50, 2005. View at Publisher · View at Google Scholar · View at Scopus
  156. P. Cifelli and A. A. Grace, “Pilocarpine-induced temporal lobe epilepsy in the rat is associated with increased dopamine neuron activity,” The International Journal of Neuropsychopharmacology, vol. 15, no. 7, pp. 957–964, 2012. View at Google Scholar
  157. D. J. Lodge and A. A. Grace, “Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia,” Trends in Pharmacological Sciences, vol. 32, no. 9, pp. 507–513, 2011. View at Google Scholar
  158. C. A. Tamminga, S. Southcott, C. Sacco, A. D. Wagner, and S. Ghose, “Glutamate dysfunction in hippocampus: relevance of dentate gyrus and CA3 signaling,” Schizophrenia Bulletin, vol. 38, no. 5, pp. 927–935, 2012. View at Google Scholar
  159. C. O. Lacefield, V. Itskov, T. Reardon, R. Hen, and J. A. Gordon, “Effects of adult-generated granule cells on coordinated network activity in the dentate gyrus,” Hippocampus, vol. 22, no. 1, pp. 106–116, 2012. View at Google Scholar
  160. D. A. Henze, N. N. Urban, and G. Barrionuevo, “The multifarious hippocampal mossy fiber pathway: a review,” Neuroscience, vol. 98, no. 3, pp. 407–427, 2000. View at Publisher · View at Google Scholar · View at Scopus
  161. J. Song, K. M. Christian, G. Ming, and H. Song, “Modification of hippocampal circuitry by adult neurogenesis,” Developmental Neurobiology, vol. 72, no. 7, pp. 1032–1043, 2012. View at Google Scholar
  162. A. A. Grace, S. B. Floresco, Y. Goto, and D. J. Lodge, “Regulation of firing of dopaminergic neurons and control of goal-directed behaviors,” Trends in Neurosciences, vol. 30, no. 5, pp. 220–227, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. I. I. Gottesman and T. D. Gould, “The endophenotype concept in psychiatry: etymology and strategic intentions,” The American Journal of Psychiatry, vol. 160, no. 4, pp. 636–645, 2003. View at Publisher · View at Google Scholar · View at Scopus