报告摘要：

Lewy bodies, a pathological hallmark of Parkinson’s disease, are α-synuclein-enriched cytoplasmic inclusions that drive progressive neurodegeneration. A long-standing yet unmet goal has been the visualization of these inclusions in live brains and measurements of their pathological effects on individual neurons. Here, we developed genetically encoded reporters and knock-in mouse lines to achieve this goal. The reporters exhibited a 6-fold increase in fluorescence upon incorporation into α-synuclein inclusions. They reliably reflected α-synuclein inclusion propagation in the cortex of awake mice. Coupled with Ca2+ imaging and whole-cell recording, the reporters enabled measurement of the pathological effects of α-synuclein inclusions on neuronal activity and synaptic function. They can be selectively targeted to specific neuronal subtypes, facilitating measuring pathological effects on transcriptomes and metabolomes at the single-cell level. Overall, these reporters provide an opportunity to directly visualize α-synuclein inclusions in live brains and support various applications for measuring their pathological effects on individual neurons.

个人简介：

曹鹏博士，北京生命科学研究所高级研究员。国家杰出青年科学基金，科技部中青年科技创新领军人才。2012年回国担任独立PI，课题组聚焦于机体防御反应的神经机制研究。近十年的工作初步揭示了机体产生生理和病理防御反应的神经机制。作为通讯作者，研究成果发表在 Science、Cell、Nature Neuroscience 和 Neuron 等学术刊物。获得新基石科学基金会“科学探索奖 ”和张香桐神经科学青年科学家奖。