title: Discrete molecular states in the brain accompany changing responses to a vocal signal.
abstract: New experiences can trigger changes in gene expression in the brain. To understand this phenomenon better, we studied zebra finches hearing playbacks of birdsong. Earlier research had shown that initial playbacks of a novel song transiently increase the ZENK (ZIF-268, EGR1, NGFIA, KROX-24) mRNA in the auditory forebrain, but the response selectively habituates after repetition of the stimulus. Here, using DNA microarray analysis, we show that novel song exposure induces rapid changes in thousands of RNAs, with even more RNAs decreasing than increasing. Habituation training leads to the emergence of a different gene expression profile a day later, accompanied by loss of essentially all of the rapid "novel" molecular responses. The novel molecular profile is characterized by increases in genes involved in transcription and RNA processing and decreases in ion channels and putative noncoding RNAs. The "habituated" profile is dominated by changes in genes for mitochondrial proteins. A parallel proteomic analysis [2-dimensional difference gel electrophoresis (2D-DIGE) and sequencing by mass spectrometry] also detected changes in mitochondrial proteins, and direct enzyme assay demonstrated changes in both complexes I and IV in the habituated state. Thus a natural experience, in this case hearing the sound of birdsong, can lead to major shifts in energetics and macromolecular metabolism in higher centers in the brain.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, IL 61801, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Dong
authors.forename: Kirstin L
authors.initials: KL
authors.lastname: Replogle
authors.forename: Linda
authors.initials: L
authors.lastname: Hasadsri
authors.forename: Brian S
authors.initials: BS
authors.lastname: Imai
authors.forename: Peter M
authors.initials: PM
authors.lastname: Yau
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodriguez-Zas
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Southey
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
authors.forename: David F
authors.initials: DF
authors.lastname: Clayton
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal; D001681:Biological Assay; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D046369:Finches / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006185:Habituation, Psychophysiologic / Q000235:genetics; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014828:Vocalization, Animal / Q000502:physiology*
chemical_list: D030161:Avian Proteins; D007473:Ion Channels; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014157:Transcription Factors