Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences

Masashi Tanak, Jonnathan Singh Alvarado, Malavika Murugan, Richard Mooney

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The basal ganglia (BG) promote complex sequential movements by helping to select elementary motor gestures appropriate to a given behavioral context. Indeed, Huntington's disease (HD),which causes striatal atrophy in the BG, is characterized by hyperkinesia and chorea. How striatal cell loss alters activity in the BG and downstream motor cortical regions to cause these disorganized movements remains unknown. Here, we show that expressing the genetic mutation that causes HD in a song-related region of the songbird BG destabilizes syllable sequences and increases overall vocal activity, but leave the structure of individual syllables intact. These behavioral changes are paralleled by the selective loss of striatal neurons and reduction of inhibitory synapses on pallidal neurons that serve as the BG output. Chronic recordings in singing birds revealed disrupted temporal patterns of activity in pallidal neurons and downstream cortical neurons. Moreover, reversible inactivation of the cortical neurons rescued the disorganized vocal sequences in transfected birds. These findings shed light on a key role of temporal patterns of cortico-BG activity in the regulation of complex motor sequences and show how a genetic mutation alters cortico-BG networks to cause disorganized movements.

Original languageEnglish
Pages (from-to)E1720-E1727
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number12
DOIs
Publication statusPublished - 2016 Mar 22
Externally publishedYes

Keywords

  • Basal ganglia
  • Huntington's disease
  • Motor sequence
  • Songbird
  • Vocalization

ASJC Scopus subject areas

  • General

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