The Neurobiology of Vocal Communication With Implications for Neurodegenerative Diseases Such As Parkinson’s Disease

Abstract

Communication is essential for the transmission of important environmental or social cues such as the presence of predators, coordinating behaviors within social communities, and conveying information about personal well-being. A broad range of animal species are able to communicate using either vocal or non-vocal cues. The underlying neural anatomy for vocal communication is well-characterized in specific species like zebra finches and humans. However, the underlying neurogenetics of vocal communication is not well understood, especially in the context of neurodegenerative diseases. A handful of vocal-related genes have been identified that are causatively linked to deteriorated vocal quality, including FOXP2, associated with childhood verbal dyspraxia. These genes are highly expressed in vocal-dedicated brain regions. Unlike the well-characterized FOXP2 gene, it is unclear how neurodegenerative disease-associated genes such as the Parkinsonian gene, SNCA, cause vocal deterioration. Whereas, FOXP2’s protein is involved in neurodevelopment, SNCA’s cognate protein, alpha-synuclein, is involved in neurotransmission and cellular trafficking. Mutations in SNCA associated with Parkinson’s disease (PD) can also impair voice and speech in humans. Thus, both genes are critically important for function of vocal centers in the brain, but it is unclear how they affect these regions, especially SNCA. In Chapter One, I review (1) the neuroethology and neurobiology of vocal behavior across songbirds, rodents, and humans; (2) the neurogenetics of vocal behavior in healthy and diseased states; and finally (3) the circuit and molecular mechanisms underlying neurodegenerative diseases such as PD. In Chapter Two, I describe my novel genetic model to study Parkinsonian vocal deficits using zebra finches. In Chapter Three, I describe novel behavioral changes observed in the Thy-1 mouse transgenic model of PD. Lastly, in Chapter Four, I summarize my findings and propose a molecular model of Parkinsonian vocal dysfunction.