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A molecular neuroethological approach for identifying and characterizing a cascade of behaviorally regulated genes.

Songbirds have one of the most accessible neural systems for the study of brain mechanisms of behavior. However, neuroethological studies in songbirds have been limited by the lack of high-throughput molecular resources and gene-manipulation tools. To overcome these limitations, we constructed 21 regular, normalized, and subtracted full-length cDNA libraries from brains of zebra finches in 57 developmental and behavioral conditions in an attempt to clone as much of the brain transcriptome as possible. From these libraries, approximately 14,000 transcripts were isolated, representing an estimated 4,738 genes. With the cDNAs, we created a hierarchically organized transcriptome database and a large-scale songbird brain cDNA microarray. We used the arrays to reveal a set of 33 genes that are regulated in forebrain vocal nuclei by singing behavior. These genes clustered into four anatomical and six temporal expression patterns. Their functions spanned a large range of cellular and molecular categories, from signal transduction, trafficking, and structural, to synaptically released molecules. With the full-length cDNAs and a lentiviral vector system, we were able to overexpress, in vocal nuclei, proteins of representative singing-regulated genes in the absence of singing. This publicly accessible resource can now be used to study molecular neuroethological mechanisms of behavior.

Pubmed ID: 17018643


  • Wada K
  • Howard JT
  • McConnell P
  • Whitney O
  • Lints T
  • Rivas MV
  • Horita H
  • Patterson MA
  • White SA
  • Scharff C
  • Haesler S
  • Zhao S
  • Sakaguchi H
  • Hagiwara M
  • Shiraki T
  • Hirozane-Kishikawa T
  • Skene P
  • Hayashizaki Y
  • Carninci P
  • Jarvis ED


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

October 10, 2006

Associated Grants

  • Agency: NIH HHS, Id: DP1 OD000448
  • Agency: NIH HHS, Id: DP1 OD000448-01
  • Agency: NIDCD NIH HHS, Id: R01 DC007218
  • Agency: NIDCD NIH HHS, Id: R01 DC007218-01A1
  • Agency: NIDCD NIH HHS, Id: R01 DC007218-02
  • Agency: NIDCD NIH HHS, Id: R01 DC007218-03
  • Agency: NIDCD NIH HHS, Id: R01 DC007218-04
  • Agency: NIMH NIH HHS, Id: R01 MH070712
  • Agency: NIMH NIH HHS, Id: R01 MH070712-02
  • Agency: NIDCD NIH HHS, Id: R01DC7218

Mesh Terms

  • Animals
  • Behavior, Animal
  • Chickens
  • Ethology
  • Female
  • Finches
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Male
  • Molecular Sequence Data
  • Nervous System Physiological Phenomena
  • Vocalization, Animal