Drosophila PQBP1 regulates learning acquisition at projection neurons in aversive olfactory conditioning.
Polyglutamine tract-binding protein-1 (PQBP1) is involved in the transcription-splicing coupling, and its mutations cause a group of human mental retardation syndromes. We generated a fly model in which the Drosophila homolog of PQBP1 (dPQBP1) is repressed by insertion of piggyBac. In classical odor conditioning, learning acquisition was significantly impaired in homozygous piggyBac-inserted flies, whereas the following memory retention was completely normal. Mushroom bodies (MBs) and antennal lobes were morphologically normal in dPQBP1-mutant flies. Projection neurons (PNs) were not reduced in number and their fiber connections were not changed, whereas gene expressions including NMDA receptor subunit 1 (NR1) were decreased in PNs. Targeted double-stranded RNA-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. HDAC (histone deacetylase) inhibitors, SAHA (suberoylanilide hydroxamic acid) and PBA (phenylbutyrate), that upregulated NR1 partially rescued the learning disturbance. Collectively, these findings identify dPQBP1 as a novel gene regulating learning acquisition at PNs.
Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Takuya
T
Tamura
Daisuke
D
Horiuchi
Yi-Chung
YC
Chen
Masaki
M
Sone
Tomoyuki
T
Miyashita
Minoru
M
Saitoe
Natsue
N
Yoshimura
Ann-Shyn
AS
Chiang
Hitoshi
H
Okazawa
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D015152:Blotting, Northern; D003216:Conditioning, Operant / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004330:Drosophila / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology; D024521:Mushroom Bodies / Q000502:physiology; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009842:Oligopeptides / Q000235:genetics* / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012903:Smell / Q000235:genetics* / Q000502:physiology*
D056572:Histone Deacetylase Inhibitors; C409466:NR1 NMDA receptor; D009842:Oligopeptides; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C407346:polyglutamine-binding protein 1; D012313:RNA; C121465:6-methyl-2-(phenylethynyl)pyridine; D018021:Lithium Chloride