α-Synuclein aggregates in corticostriatal terminals impair glutamatergic transmission in the absence of neurodegeneration

Researchers induced alpha-synuclein aggregation in the mouse M2 cortex to model Lewy pathology and examined corticostriatal projections. They found that aggregates in presynaptic terminals reduced glutamatergic transmission, even in the absence of dopaminergic neuron loss or overt neurodegeneration. This suggests that synaptic dysfunction from alpha-synuclein aggregates may precede neuronal death and contribute to early motor and cognitive symptoms. The study provides a mechanism linking cortical Lewy pathology to striatal circuit impairment, and points to synaptic targets for potential therapeutic intervention. Further work is needed to determine whether reversing aggregation can restore transmission.