Functional analysis of the habenulo-raphe pathway using genetic manipulation

â—‹Ryunosuke Amo1,2, Masakazu Agetsuma1, Masae Kinoshita1, Toshiyuki Shiraki1, Shin-ichi Higashijima3, Masaru Matsuda4, Maximiliano L Suster5, Koichi Kawakami5, Toshio Ohshima2, Hidenori Aizawa1, and Hitoshi Okamoto1,2

1 )RIKEN Brain Science Institute, 2) Department of Life Science and Medical Bioscience, Waseda University, 3) NIPS, Okazaki Institute for Integrative Bioscience, 4 )Center for Bioscience Research and Education, Utsunomiya University, 5 )Division of Molecular and Developmental Biology, National Institute of Genetics

The habenula is an evolutionary conserved structure located in the dorsal most part of the diencephalon. In mammals, the habenula is divided into two parts the lateral and medial habenula. The lateral habenula receives input from the basal ganglia and sends its information to serotonergic neurons in the raphe and dopaminergic neurons in the VTA and the substantia nigra. Although recent studies identified a role for the habenula in regulation of negative reward information and depression-related behavior, the function of the habenulo-raphe pathway is largely unknown. The medial habenula also indirectly sends information to the raphe via the interpeduncular nucleus. Specific modulation of neural activity in the subnuclei of the habenula is necessary to reveal the function of the habenulo-raphe pathway. We have shown that the habenula sub-divisions are conserved between mammals and zebrafish (Amo et al., 2010). To control neural transmission specifically in the subnuclei of habenula, we established the transgenic lines by using BAC clones for genes specifically expressed in the habenula identified by GeneChip analysis. Now we are analyzing function of the habenula by using those lines.