Vocalization deficits in mice over-expressing alpha-synuclein, a model of pre-manifest parkinson's disease

Laura M. Grant, Franziska Richter, Julie E. Miller, Stephanie A. White, Cynthia M. Fox, Chunni Zhu, Marie Francoise Chesselet, Michelle R. Ciucci

Research output: Contribution to journalArticle

26 Scopus citations


Communication and swallowing deficits are common in Parkinson's disease (PD). Evidence indicates that voice and speech dysfunction manifest early, prior to motor deficits typically associated with striatal dopamine loss. Unlike deficits in the extremities, cranial sensorimotor deficits are refractory to standard dopamine-related pharmacological and surgical interventions, thus the mechanisms underlying vocal deficits are unclear. Although neurotoxin models have provided some insight, they typically model nigrostriatal dopamine depletion and are therefore limited. Widespread alpha-synuclein (aSyn) pathology is common to familial and sporadic PD, and transgenic mouse models based on aSyn overexpression present a unique opportunity to explore vocalization deficits in relation to extrastriatal, nondopaminergic pathologies. Specifically, mice overexpressing human wild-type aSyn under a broad neuronal promoter (Thy1-aSyn) present early, progressive motor and nonmotor deficits starting at 2-3 months, followed by parkinsonism with dopamine loss at 14 months. We recorded ultrasonic vocalizations from Thy1-aSyn mice and wild-type (WT) controls at 2-3, 6-7, and 9 months. Thy1-aSyn mice demonstrated early, progressive vocalization deficits compared with WT. Duration and intensity of calls were significantly reduced and call profile was altered in the Thy1-aSyn mice, particularly at 2-3 months. Call rate trended toward a more drastic decrease with age in the Thy1-aSyn mice compared with WT. Alpha-synuclein pathology is present in the periaqueductal gray and may underlie the manifestation of vocalization deficits. These results indicate that aSyn overexpression can induce vocalization deficits at an early age in mice and provides a new model for studying the mechanisms underlying cranial sensorimotor deficits and treatment interventions for PD.

Original languageEnglish (US)
Pages (from-to)110-121
Number of pages12
JournalBehavioral Neuroscience
Issue number2
StatePublished - Apr 1 2014


  • Alpha-synuclein
  • Cranial sensorimotor deficits
  • Mouse
  • Parkinson's disease
  • Ultrasonic vocalization

ASJC Scopus subject areas

  • Behavioral Neuroscience

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    Grant, L. M., Richter, F., Miller, J. E., White, S. A., Fox, C. M., Zhu, C., Chesselet, M. F., & Ciucci, M. R. (2014). Vocalization deficits in mice over-expressing alpha-synuclein, a model of pre-manifest parkinson's disease. Behavioral Neuroscience, 128(2), 110-121. https://doi.org/10.1037/a0035965