Site-specific seeding of Lewy pathology induces distinct pre-motor cellular and dendritic vulnerabilities in the cortex.

ABSTRACT: Circuit-based biomarkers distinguishing the gradual progression of Lewy pathology across synucleinopathies remain unknown. Here, we show that seeding of α-synuclein preformed fibrils in mouse dorsal striatum and motor cortex leads to distinct prodromal-phase cortical dysfunction across months. Our findings reveal that while both seeding sites had increased cortical pathology and hyperexcitability, distinct differences in electrophysiological and cellular ensemble patterns were crucial in distinguishing pathology spread between the two seeding sites. Notably, while beta-band spike-field-coherence reflected a significant increase beginning in Layer-5 and then spreading to Layer-2/3, the rate of entrainment and the propensity of stochastic beta-burst dynamics was markedly seeding location-spe

SUBMITTER: Khan HF 

PROVIDER: S-EPMC11685769 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature