title: Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation.
abstract: Memory is initially labile and gradually consolidated over time through new protein synthesis into a long-lasting stable form. Studies of odor-shock associative learning in Drosophila have established the mushroom body (MB) as a key brain structure involved in olfactory long-term memory (LTM) formation. Exactly how early neural activity encoded in thousands of MB neurons is consolidated into protein-synthesis-dependent LTM remains unclear. Here, several independent lines of evidence indicate that changes in two MB vertical lobe V3 (MB-V3) extrinsic neurons are required and contribute to an extended neural network involved in olfactory LTM: (i) inhibiting protein synthesis in MB-V3 neurons impairs LTM; (ii) MB-V3 neurons show enhanced neural activity after spaced but not massed training; (iii) MB-V3 dendrites, synapsing with hundreds of MB α/β neurons, exhibit dramatic structural plasticity after removal of olfactory inputs; (iv) neurotransmission from MB-V3 neurons is necessary for LTM retrieval; and (v) RNAi-mediated down-regulation of oo18 RNA-binding protein (involved in local regulation of protein translation) in MB-V3 neurons impairs LTM. Our results suggest a model of long-term memory formation that includes a systems-level consolidation process, wherein an early, labile olfactory memory represented by neural activity in a sparse subset of MB neurons is converted into a stable LTM through protein synthesis in dendrites of MB-V3 neurons synapsed onto MB α lobes.
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Tsung-Pin
authors.initials: TP
authors.lastname: Pai
authors.forename: Chun-Chao
authors.initials: CC
authors.lastname: Chen
authors.forename: Hui-Hao
authors.initials: HH
authors.lastname: Lin
authors.forename: An-Lun
authors.initials: AL
authors.lastname: Chin
authors.forename: Jason Sih-Yu
authors.initials: JS
authors.lastname: Lai
authors.forename: Pei-Tseng
authors.initials: PT
authors.lastname: Lee
authors.forename: Tim
authors.initials: T
authors.lastname: Tully
authors.forename: Ann-Shyn
authors.initials: AS
authors.lastname: Chiang
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D005786:Gene Expression Regulation; D057567:Memory, Long-Term / Q000502:physiology*; D008959:Models, Neurological; D024521:Mushroom Bodies / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; C467328:FMR1 protein, Drosophila; C529066:Orb2 protein, Drosophila; C089932:orb protein, Drosophila; C074333:pum protein, Drosophila; C069927:stau protein, Drosophila
keywords: CPEB; CREB; PUM; STAU; fragile X mental retardation