DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats

Heekyung Lee, Eunchai Kang, Douglas GoodSmith, Do Yeon Yoon, Hongjun Song, James Knierim, Guo Li Ming, Kimberly M. Christian

Research output: Contribution to journalArticle

Abstract

Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function.

Original languageEnglish (US)
Article number93
JournalFrontiers in Systems Neuroscience
Volume9
Issue numberJune
DOIs
StatePublished - Jun 25 2015

Fingerprint

Neurogenesis
Psychiatry
Dentate Gyrus
Genes
Schizophrenia
Carisoprodol
Dendrites
Nervous System Diseases
Hypertrophy
Phenotype
Neurons
Brain
Growth

Keywords

  • Adult neurogenesis
  • Dentate gyrus
  • DISC1
  • Hippocampus
  • Psychiatric disorders
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience
  • Developmental Neuroscience

Cite this

Lee, H., Kang, E., GoodSmith, D., Yoon, D. Y., Song, H., Knierim, J., ... Christian, K. M. (2015). DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats. Frontiers in Systems Neuroscience, 9(June), [93]. https://doi.org/10.3389/fnsys.2015.00093

DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats. / Lee, Heekyung; Kang, Eunchai; GoodSmith, Douglas; Yoon, Do Yeon; Song, Hongjun; Knierim, James; Ming, Guo Li; Christian, Kimberly M.

In: Frontiers in Systems Neuroscience, Vol. 9, No. June, 93, 25.06.2015.

Research output: Contribution to journalArticle

Lee, H, Kang, E, GoodSmith, D, Yoon, DY, Song, H, Knierim, J, Ming, GL & Christian, KM 2015, 'DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats', Frontiers in Systems Neuroscience, vol. 9, no. June, 93. https://doi.org/10.3389/fnsys.2015.00093
Lee, Heekyung ; Kang, Eunchai ; GoodSmith, Douglas ; Yoon, Do Yeon ; Song, Hongjun ; Knierim, James ; Ming, Guo Li ; Christian, Kimberly M. / DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats. In: Frontiers in Systems Neuroscience. 2015 ; Vol. 9, No. June.
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