Developmental Gene Regulation
Senior Team Leader
Emotion, Habenula, Left-right asymmetry
1. Investigating the role of the evolutionary conserved limbic circuit within vertebrates.
We investigate the role of neural circuits that control the selection and execution of emotional behaviors. We study fish and rodents using various methods including the genetics, molecular and cell biology and physiology. In mammalian telencephalon, the cortico-basal ganglia circuit is thought to be involved in selection of the behavioral programs (Figure A). External physical information and related emotional information enter the cortico basal ganglia circuit via the hippocampus and amygdala, respectively, and modulate this circuit to establish ensembles of neurons encoding various behavioral programs (Figure A). However, it is still unclear how a particular ensemble of neurons becomes selected through this neural circuit.
Zebrafish (teleosts) have the simplest neural system in the vertebrates. By the movement of the neural tube called eversion, the hippocampus and amygdala in fish become located in the medial and lateral part of the telencephalon, respectively (Figure B), showing the inside out position with respect to that of mammals. Furthermore, it has been recently shown that the zebrafish telencephalon may contain the cortico-basal ganglia circuit where the behavioral programs become stored. Zebrafish brain is so small that we can analyze the neural activities of the entire cortico-basal ganglia circuit by the calcium imaging. By combining with the optogenetics to interfere the activity of the cortico-basal ganglia circuit, we believe that the common neural mechanisms between fish and mammals which underly the establishment of the memory for the behavioral program will be unveiled.
2. Exploring the role of habenula in emotional behaviors.
We also focus on the habenula, a nucleus located in the dorsal midbrain. Mammalian habenula consists of the medial and lateral nucleus (Figure C, E), which control directly and indirectly dopaminergic neurons in the ventral tegmental area and serotonergic neurons in the Raphe, respectively (Figure C, D). The medial and lateral parts of the habenula in mammals correspond to the dorsal and ventral habenula in fish, respectively (Figure E), and the connectivity of each subnucleus is well conserved between fish and mammals (Figure D, E). We are trying to reveal the role of this well conserved habenula circuit in the control of emotional behaviors. In deed, when the zebrafish dorsal habenula is inactivated by the neurotoxin, fish tend to select the freezing instead of the agitating behavior in the cued-fear conditioning (Figure F). We study the role of the habenula in switching of the emotional behaviors, the adaptive fear learning, the aggressiveness or the social dominant-subordinate relationships, using zebrafish, rats and mice.
3. Studying the mechanism of the sensory neuron development and adult neurogenesis.
We study the role of Trk signaling pathway in the sensory neuron development and adult neurogenesis using zebrafish and mice.
Ohata S, Aoki R, Kinoshita S, Yamaguchi M, Tsuruoka-Kinoshita S, Tanaka H, Wada H, Watabe S, Tsuboi T, Masai I, and Okamoto H: "Dual roles of Notch in regulation of apically restricted mitosis and apicobasal polarity of neuroepithelial cells.", Neuron, 69(2), 215-30 (2011)
Agetsuma M, Aizawa H, Aoki T, Nakayama R, Takahoko M, Goto M, Sassa T, Amo R, Shiraki T, Kawakami K, Hosoya T, Higashijima S, and Okamoto H: "The habenula is crucial for experience-dependent modification of fear responses in zebrafish.", Nat Neurosci, 13(11), 1354-6 (2010)
Amo R, Aizawa H, Takahoko M, Kobayashi M, Takahashi R, Aoki T, and Okamoto H: "Identification of the zebrafish ventral habenula as a homolog of the mammalian lateral habenula.", J Neurosci, 30(4), 1566-74 (2010)
Ohata S, Kinoshita S, Aoki R, Tanaka H, Wada H, Tsuruoka-Kinoshita S, Tsuboi T, Watabe S, and Okamoto H: "Neuroepithelial cells require fucosylated glycans to guide the migration of vagus motor neuron progenitors in the developing zebrafish hindbrain.", Development, 136(10), 1653-63 (2009)
Aizawa H, Goto M, Sato T, and Okamoto H: "Temporally regulated asymmetric neurogenesis causes left-right difference in the zebrafish habenular structures.", Dev Cell, 12(1), 87-98 (2007)
Wada H, Tanaka H, Nakayama S, Iwasaki M, and Okamoto H: "Frizzled3a and Celsr2 function in the neuroepithelium to regulate migration of facial motor neurons in the developing zebrafish hindbrain.", Development, 133(23), 4749-59 (2006)
Wada H, Iwasaki M, Sato T, Masai I, Nishiwaki Y, Tanaka H, Sato A, Nojima Y, and Okamoto H: "Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos.", Development, 132(10), 2273-85 (2005)
Aizawa H, Bianco IH, Hamaoka T, Miyashita T, Uemura O, Concha ML, Russell C, Wilson SW, and Okamoto H: "Laterotopic representation of left-right information onto the dorso-ventral axis of a zebrafish midbrain target nucleus.", Curr Biol, 15(3), 238-43 (2005)
Ando H, Furuta T, Tsien RY, and Okamoto H.: "Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos.", Nat Genet, 28(4), 317-25 (2001)
Segawa H, Miyashita T, Hirate Y, Higashijima S, Chino N, Uyemura K, Kikuchi Y, and Okamoto H.: "Functional repression of Islet-2 by disruption of complex with Ldb impairs peripheral axonal outgrowth in embryonic zebrafish.", Neuron, 30(2), 423-36 (2001)
- Nov. 21, 2014 Out of danger: a neural basis for avoiding threats Hitoshi Okamoto, M.D., Ph.D., Developmental Gene Regulation
- May. 17, 2013 Fishing for Memories Hitoshi Okamoto, M.D., Ph.D., Developmental Gene Regulation
- May. 15, 2013 Getting a grip on sleep Hitoshi Okamoto, M.D., Ph.D., Developmental Gene Regulation
- Oct. 11, 2010 Study identifies neural pathways governing switching of fear responses in the zebrafish Hitoshi OKAMOTO, M.D., Ph.D., Developmental Gene Regulation
- Jan. 9, 2007 Timing is everything Hitoshi OKAMOTO, M.D., Ph.D., Developmental Gene Regulation
- Jan. 20, 2005 Mechanisms for Brain Asymmetry Hitoshi OKAMOTO, M.D., Ph.D., Developmental Gene Regulation