Behavioral genetics

  Axonal netrin-Gs transneuronally determine
  lamina-specific subdendritic segments.

  Nishimura-Akiyoshi S, Niimi K, Nakashiba T, Itohara S.
  Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14801-6.

  Rac-GAP alpha-chimerin regulates
  motor-circuit formation as a key mediator
  of EphrinB3/EphA4 forward signaling.

  Iwasato T, Katoh H, Nishimaru H, Ishikawa Y, Inoue H,
  Saito YM, Ando R, Iwama M, Takahashi R, Negishi M,
  Itohara S.
  Cell. 2007 Aug 24;130(4):742-53.    

  Molecular evidence for two-stage learning
  and partial laterality
in eyeblink conditioning
  of mice.

  Park JS, Onodera T, Nishimura S, Thompson RF,
  Itohara S.
  Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5549-54.    

  Glial protein S100B modulates long-term
  neuronal syna
ptic plasticity.

  Nishiyama H, Knopfel T, Endo S, Itohara S.
  Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):4037-42.    

  a novel glycosyl phosphatidylinositol-linked
  mammalian netrin that is functionally
  divergent from classical netrins.

  Nakashiba T, Ikeda T, Nishimura S, Tashiro K, Honjo T,
  Culotti JG, Itohara S.
  J Neurosci. 2000 Sep 1;20(17):6540-50.    

  Cortex-restricted disruption of NMDAR1 impairs
  neuronal patterns in the barrel cortex.

  Iwasato T, Datwani A, Wolf AM, Nishiyama H, Taguchi Y,
  Tonegawa S, Knöpfel T, Erzurumlu RS, Itohara S.
  Nature. 2000 Aug 17;406(6797):726-31.    


     The integration of complex external and internal information by the brain is important for controlling animal behavior. Highly organized molecular and cellular networks underlie this integration. These networks are largely defined by genetic factors and partly by environmental factors, and their subtle differences among individuals underlie differences in personality and temperament. Abnormalities in these networks caused by various factors, including injury, infection, social and physical stress, and genetic factors, might result in cognitive deficits and various mental disorders in humans. We are interested in learning how highly organized networks are established in the mammalian central nervous system (CNS), how the networks are modulated by environmental factors, and the mechanisms that underlie the integration of and/or differentiation of distinct information inputs. Mutant animals generated by reverse genetics are indispensable for examining these issues, because they allow for the study of an unambiguous cause-effect relationship at any phenotype level. Among animal models, mice have particular advantages, such as a phylogenetic similarity with humans and high efficiency for breeding/housing. Recent progress in mouse behavioral neuroscience, importantly, has revealed their highly evolved abilities, including cognition and emotion-related behaviors.

      Novel mouse models are promising for cutting-edge neuroscience research. To facilitate this type of research strategy, our laboratory develops and refines genetic engineering methods and provides mice with novel genetic traits for studying specific topics. Our current interests include the elucidation of molecular and cellular mechanisms underlying neuronal circuit formation as well as those underlying use-dependent processes during CNS development and in learning and memory in adulthood. We are also gradually expanding our research to analyze neuronal circuits and molecular mechanisms underlying mental disorders. Multiple mouse lines established in this laboratory show behavioral phenotypes that might account for some mental states observed in humans. The neuron-astrocyte interaction is currently a cutting-edge research topic that might be involved in all of the subjects mentioned above. Methods and resources that we have developed are generally applicable for various projects and studies pursued by others. To take full advantage of these newly developed mouse genetic methods, we have worked in a wide-range of neuroscience research areas (structure to function), e.g., molecular bases of the formation and activity-dependent modification of neuronal circuits, plasticity, and behavior.