THE SILENCE BEFORE THE STORM: UNDERSTANDING EARLIER PARKINSON'S DISEASE DETECTION THROUGH VOCAL AND MOLECULAR ANALYSIS

Abstract

Vocal impairments are early and underexplored symptoms of Parkinson's Disease (PD), often preceding limb motor deficits. This study uses the zebra finch, a songbird with a well-defined vocal-motor circuit, to investigate how alpha-synuclein (a-syn) aggregation contributes to vocal dysfunction in a PD model. Adult male finches received AAV-mediated overexpression of human a-syn in Area X, a basal ganglia song nucleus. We developed a novel metric, the Border Expression Ratio (BER), to quantify regional a-syn accumulation. In the use of BER, we used a ratio of the a-syn fluorescence values outside of Area X versus inside Area X. A lower BER ratio means a higher a-syn protein expression inside Area X. Compared to controls, a-syn overexpression led to significant BER reduction. These molecular changes were associated with alterations in song features such as syllable duration, entropy, and amplitude. Our findings highlight the zebra finch as a powerful model for linking a-syn pathology to early vocal deficits in PD and offer a new framework for studying neurodegeneration in behaviorally relevant circuits.