演題番号 : P1-m23
田村 拓也 / Takuya Tamura:1 堀内 大輔 / Daisuke Horiuchi:1 Yi-Chung Chen:2 曽根 雅紀 / Masaki Sone:1 宮下 知之 / Tomoyuki Miyashita:3 齊藤 実 / Minoru Saitoe:3 吉村 奈津恵 / Natsue Yoshimura:1 Ann-Shyn Chiang:2 岡澤 均 / Hitoshi Okazawa:1
1:東京医科歯科大学 難治疾患研究所 / Medical Reserch Institute, Tokyo Medical and Dental University, Tokyo 2:国立清華大学 / Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan, ROC 3:東京都神経科学総合研究所 / Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan
Drosophila memory is most extensively studied by classical aversive olfactory conditioning. It is generally believed that conditioned stimuli and un-conditioned stimuli are combined in third-order olfactory pathway neurons, Kenyon cells in mushroom bodies (MBs), and the plasticity of these cells critically regulates memory formation in classical olfactory conditioning. Hence, most studies have been focusing on the plasticity of MBs and the memory genes expressed in MBs. However, several recent reports have suggested projection neurons (PNs) might also regulate learning and memory. There is an increase in literature that suggests that PNs carry out an important computation roles for sensory coding in MBs. However, little number of memory gene which works in PNs have been reported. In this presentation, we report a novel memory gene which works in PNs. Polyglutamine tract-binding protein-1 (PQBP1) is involved in the transcription-splicing coupling and its mutations cause a group of human mental retardation (MR) syndromes. We generated a fly model in which the drosophila homologue of PQBP1 (dPQBP1) is repressed. In classical odor conditioning, learning acquisition was significantly impaired in homozygous mutant flies whilst the following memory retention was completely normal. MBs and antennal lobes were morphologically normal in dPQBP1-mutant flies. PNs were not reduced in number and their fiber connections were not changed, whereas gene expressions including NMDAR subunit 1 (NR1) were decreased in PNs. Targeted dsRNA-mediated silencing of dPQBP1 in PNs, but not in MBs, similarly disrupted learning acquisition. NR1 overexpression in PNs rescued the learning disturbance of dPQBP1-mutants. Histone deacetylase (HDAC) inhibitors, SAHA and PBA, that upregulated NR1 partially rescued the learning disturbance. Collectively, these findings identify dPQBP1 as a novel gene regulating learning acquisition at PNs.