Laboratory for Behavioral Genetics

Animal behavior relies on the integration of complex external and internal information in the brain. Highly organized molecular and cellular networks underlie this integration. These networks are defined largely 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 genetics, might result in cognitive deficits and various mental disorders. 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 and/or differentiation of distinct information inputs. Mutant mice 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. In our laboratory, we have developed and refined genetic engineering methods to produce mice with the required novel genetic traits. Our current aims include the elucidation of molecular and cellular mechanisms underlying attention and impulsivity. We focus on neuronal circuits that express Netrin G1 or Netrin-G2. Neuron-astrocyte interactions are also a focus of study in our laboratory.

Research Subjects

• Molecular mechanisms of neural network formation
• Neuronal networks underlying attention and related behaviors
• Neuronal circuit mechanisms for REM sleep and its implication
• Roles of astrocytes inhiger brain functions
• Genetic tools for analyzing neuronal network functions

Publications

1. Sadakata T, Shinoda Y, Oka M, Sekine Y, Sato Y, Tanaka M, Itohara S, and Furuichi T.:
   "Reduced axonal localization of a Caps2 splice variant impairs polarization of BDNF release and causes autistic-like behavior in mice"
   Proc Natl Acad Sci USA 109(51):21104-21109, 2012
2. Tanaka, M., Shih, P-Y., Gomi H., Yoshida T., Nakai J., Ando, R., Furuichi, T., Mikoshiba, K., Semyanov, A., and Itohara, S.:
   "Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses"
   Mol. Brain, 6:6 (2013)
3. Sano, Y., Ornthanalai, V.G., Yamada, K., Homma, C., Suzuki, H., Suzuki, T., Murphy, N.P., and Itohara, S.:
   "X11-like protein deficiency is associated with impaired conflict resolution in mice"
   J. Neurosci., 29, 5584-5596 (2009)
4. Iwasato, T., Inan, M., Kanki, H., Erzurumlu, R., Itohara, S., and Crair, M.C.:
   "Cortical adenylylyl cyclase 1 is required for thalamocortical synapse maturation and proper layer IV neuronal morphology during barrel map development"
   J. Neurosci., 28, 5931-5943 (2008)
5. Nishimura-Akiyoshi, S., Niimi, K., Nakashiba, T. and Itohara, S.:
   "Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments"
   Proc. Natl. Acad. Sci. USA, 104, 14801-14806 (2007)
6. Iwasato, T., Katoh, H., Nishimaru, H., Ishikawa, Y., Inoue, H., Saito, Y.M., Ando, R., Iwama, M., Takahashi, R., Negishi, M., and Itohara, S.:
   "Rac-GAP alpha-chimerin regulates motor-circuit formation as a key mediator of ephrineB3/EphA4 forward signaling"
   Cell 130, 742-753 (2007)
7. Nishiyama, H., Knopfel, T., Endo, S., and Itohara, S.:
   "Glial protein S100B modulates long term neuronal synaptic plasticity"
   Proc. Natl. Acad. Sci. USA, 99, 4037-4042 (2002)
8. Nakashiba, T., Nishimura, S., Ikeda, T., and Itohara, S.:
   "Complementary expression and neurite outgrowth activity of netrin-G subfamily members"
   Mech. Dev., 111, 47-60 (2002)
9. Iwasato, T., Datwani, A., Wolf, A.M., Nishiyama, H., Taguchi, Y., Tonegawa, S., Knopfel, T., Erzurumlu, R.S., and Itohara, S.:
   "Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex"
   Nature 406, 726-731 (2000)
10. Nakashiba, T., Ikeda, T., Nishimura, S., Tashiro, K., Honjo, T. Culotti, J.G., and Itohara, S.:
    "Netrin-G1: a novel GPI-linked mammalian netrin that is functionally divergent from classical netrins"
    J. Neurosci., 20, 6540-6550 (2000)