Acute social isolation alters neurogenomic state in songbird forebrain

Julia George, Zachary Bell, Daniel Condliffe, Kirstin Doher, Teresa Abaurrea, Karen Spencer, Albertine Leitao, Manfred Gahr, Paul Hurd, David F. Clayton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
1 Downloads (Pure)


Prolonged social isolation has negative effects on brain and behavior in humans and other social organisms, but neural mechanisms leading to these effects are not understood. Here we tested the hypothesis that even brief periods of social isolation can alter gene expression and DNA methylation in higher cognitive centers of the brain, focusing on the auditory/associative forebrain of the highly social zebra finch. Using RNA sequencing, we first identified genes that individually increase or decrease expression after isolation and observed general repression of gene sets annotated for neurotrophin pathways and axonal guidance functions. We then pursued 4 genes of large effect size: EGR1 and BDNF (decreased by isolation) and FKBP5 and UTS2B (increased). By in situ hybridization, each gene responded in different cell subsets, arguing against a single cellular mechanism. To test whether effects were specific to the social component of the isolation experience, we compared gene expression in birds isolated either alone or with a single familiar partner. Partner inclusion ameliorated the effect of solo isolation on EGR1 and BDNF, but not on FKBP5 and UTS2B nor on circulating corticosterone. By bisulfite sequencing analysis of auditory forebrain DNA, isolation caused changes in methylation of a subset of differentially expressed genes, including BDNF. Thus, social isolation has rapid consequences on gene activity in a higher integrative center of the brain, triggering epigenetic mechanisms that may influence processing of ongoing experience.
Original languageEnglish
Pages (from-to)23311-23316
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
Early online date22 Jul 2019
Publication statusPublished - 22 Sept 2020


  • Zebra finch
  • RNA-seq
  • DNA methylation
  • Isolation
  • Forebrain


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