Vocal changes in a zebra finch model of Parkinson's disease characterized by alpha-synuclein overexpression in the song-dedicated anterior forebrain pathway

• Published in: PloS one 2022-05, Vol.17 (5), p.e0265604
• Main Authors: Medina, Cesar A, Vargas, Eddie, Munger, Stephanie J, Miller, Julie E
• Format: Article
• Language: English
• Subjects: Abnormalities; Acoustics; alpha-Synuclein - genetics; Animal models; Animals; Basal ganglia; Biology and Life Sciences; Birds; Circuits; Deterioration; Finches - physiology; Forebrain; Frequency; Ganglia; Genes; Globus pallidus; Humans; Laboratory animals; Loudness; Male; Medicine and Health Sciences; Mesencephalon; Motor task performance; Movement disorders; Mutation; Neostriatum; Neurodegenerative diseases; Neuropathology; Neurosciences; Parkinson Disease; Parkinson's disease; Parkinsons disease; Pathogenesis; Physical Sciences; Prosencephalon - physiology; Proteins; Research and Analysis Methods; Social Sciences; Song; Songbirds; Synuclein; Viruses; Vocalization behavior; Vocalization, Animal - physiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0265604

Deterioration in the quality of a person's voice and speech is an early marker of Parkinson's disease (PD). In humans, the neural circuit that supports vocal motor control consists of a cortico-basal ganglia-thalamo-cortico loop. The basal ganglia regions, striatum and globus pallidus, in this loop play a role in modulating the acoustic features of vocal behavior such as loudness, pitch, and articulatory rate. In PD, this area is implicated in pathogenesis. In animal models of PD, the accumulation of toxic aggregates containing the neuronal protein alpha-synuclein (αsyn) in the midbrain and striatum result in limb and vocal motor impairments. It has been challenging to study vocal impairments given the lack of well-defined cortico-basal ganglia circuitry for vocalization in rodent models. Furthermore, whether deterioration of voice quality early in PD is a direct result of αsyn-induced neuropathology is not yet known. Here, we take advantage of the well-characterized vocal circuits of the adult male zebra finch songbird to experimentally target a song-dedicated pathway, the anterior forebrain pathway, using an adeno-associated virus expressing the human wild-type αsyn gene, SNCA. We found that overexpression of αsyn in this pathway coincides with higher levels of insoluble, monomeric αsyn compared to control finches. Impairments in song production were also detected along with shorter and poorer quality syllables, which are the most basic unit of song. These vocal changes are similar to the vocal abnormalities observed in individuals with PD.