Molecular microcircuitry underlies functional specification in a basal ganglia circuit dedicated to vocal learning

Neuron. 2012 Feb 9;73(3):537-52. doi: 10.1016/j.neuron.2012.01.005.


Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication--a complex phenotype probably supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene coexpression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ∼2,000 singing-regulated genes comprising three coexpression groups unique to area X, the basal ganglia subregion dedicated to learned vocalizations. These contained known targets of human FOXP2 and potential avian targets. We validated biological pathways not previously implicated in vocalization. Higher-order gene coexpression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that probably bear on human motor disorders, especially those affecting speech.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basal Ganglia / anatomy & histology*
  • Basal Ganglia / physiology*
  • Computational Biology
  • ELAV Proteins / genetics
  • ELAV Proteins / metabolism
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / physiology
  • Oligonucleotide Array Sequence Analysis / methods
  • Phosphopyruvate Hydratase / metabolism
  • Songbirds
  • Vocalization, Animal*


  • ELAV Proteins
  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • Nerve Tissue Proteins
  • Phosphopyruvate Hydratase