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

Publication ,  Journal Article
Tanaka, M; Singh Alvarado, J; Murugan, M; Mooney, R
Published in: Proc Natl Acad Sci U S A
March 22, 2016

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 22, 2016

Volume

113

Issue

12

Start / End Page

E1720 / E1727

Location

United States

Related Subject Headings

  • Vocalization, Animal
  • Transduction, Genetic
  • Time Factors
  • Synapsins
  • Synapses
  • Recombinant Fusion Proteins
  • Promoter Regions, Genetic
  • Organ Specificity
  • Neurons
  • Neural Pathways
 

Citation

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Tanaka, M., Singh Alvarado, J., Murugan, M., & Mooney, R. (2016). Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences. Proc Natl Acad Sci U S A, 113(12), E1720–E1727. https://doi.org/10.1073/pnas.1523754113
Tanaka, Masashi, Jonnathan Singh Alvarado, Malavika Murugan, and Richard Mooney. “Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences.Proc Natl Acad Sci U S A 113, no. 12 (March 22, 2016): E1720–27. https://doi.org/10.1073/pnas.1523754113.
Tanaka M, Singh Alvarado J, Murugan M, Mooney R. Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences. Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):E1720–7.
Tanaka, Masashi, et al. “Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences.Proc Natl Acad Sci U S A, vol. 113, no. 12, Mar. 2016, pp. E1720–27. Pubmed, doi:10.1073/pnas.1523754113.
Tanaka M, Singh Alvarado J, Murugan M, Mooney R. Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences. Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):E1720–E1727.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 22, 2016

Volume

113

Issue

12

Start / End Page

E1720 / E1727

Location

United States

Related Subject Headings

  • Vocalization, Animal
  • Transduction, Genetic
  • Time Factors
  • Synapsins
  • Synapses
  • Recombinant Fusion Proteins
  • Promoter Regions, Genetic
  • Organ Specificity
  • Neurons
  • Neural Pathways