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In Parkinson’s disease (PD), aggregation of the presynaptic protein ‘alpha-synuclein’ culminates
in the formation of Lewy bodies and eventual death of dopaminergic neurons. The resulting limb
motor dysfunction that hallmarks PD is only observed in humans and animal models once
dopamine neuron loss reaches roughly 60%. Critically, PD patients often exhibit impaired
vocalizations prior to the onset of limb motor deficits. To this end, when alpha-synuclein is
overexpressed in the zebra finch song circuit, via an adeno-associated virus (AAV), significant
song deficits are measured beginning one month post-injection. Our investigations pursue the
molecular and circuit-level pathomechanisms that lead to altered birdsong. This talk will review
the relative toxicities of various forms and conformations of alpha-synuclein and outline
experimental steps towards elucidating a pathological ‘tipping point’ for alpha-synuclein driven
changes in vocal behavior.