Kavli Affiliate: Rui Costa
| Authors: Akira Fushiki, David Ng, Zachary R. Lewis, Archana Yadav, Tatiana Saraiva, Luke A. Hammand, Christoph Wirblich, Bosiljka Tasic, Vilas Menon, Joaquim Alves da Silva and Rui M. Costa
| Summary:
In Parkinson′s disease (PD), dopaminergic neurons (DANs) in the midbrain gradually degenerate, with ventral substantia nigra pars compacta (SNc) DANs exhibiting greater vulnerability. However, it remains unclear whether specific molecular subtypes of ventral SNc DANs are more susceptible to degeneration in PD, and if they contribute to the early motor symptoms associated with the disease. We identified a subtype of Sox6+ DANs, Anxa1+, which are selectively lost earlier than other DANs, and with a time course that aligns with the development of motor symptoms in MitoPark mice. We generated a knock-in Cre mouse line for Anxa1+ DANs and showed differential anatomical inputs and outputs of this population. Further, we found that the inhibition of transmitter release in Anxa1+ neurons led to bradykinesia and tremor. Therefore, Anxa1+ is not only a biomarker of a selectively vulnerable subtype of DANs, but is also sufficient to drive early motor symptoms in Parkinson′s disease.