Dopamine Deficiency Reduces Striatal Cholinergic Interneuron Function in Models of Parkinson's Disease.

ABSTRACT: Motor and cognitive functions depend on the coordinated interactions between dopamine (DA) and acetylcholine (ACh) at striatal synapses. Increased ACh availability was assumed to accompany DA deficiency based on the outcome of pharmacological treatments and measurements in animals that were critically depleted of DA. Using Slc6a3^DTR/+ diphtheria-toxin-sensitive mice, we demonstrate that a progressive and L-dopa-responsive DA deficiency reduces ACh availability and the transcription of hyperpolarization-activated cation (HCN) channels that encode the spike timing of ACh-releasing tonically active striatal interneurons (ChIs). Although the production and release of ACh and DA are reduced, the preponderance of ACh over DA contributes to the motor deficit. The increase in striatal A

SUBMITTER: McKinley JW 

PROVIDER: S-EPMC7102938 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature