State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.

ABSTRACT: In the later stages of Parkinson's disease, patients often manifest levodopa-induced dyskinesia (LID), compromising their quality of life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this treatment gap, the intrinsic and synaptic changes in striatal spiny projection neurons (SPNs) triggered by the sustained elevation of dopamine (DA) during dyskinesia were characterized using electrophysiological, pharmacological, molecular, and behavioral approaches. Our studies revealed that the intrinsic excitability and functional corticostriatal connectivity of SPNs in dyskinetic mice oscillate between LID on- and off-states in a cell- and state-specific manner. Although triggered by levodopa, these oscillations in SPN properties d

SUBMITTER: Zhai S 

PROVIDER: S-EPMC12674127 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature