Reduced striatal M4-cholinergic signaling following dopamine loss contributes to parkinsonian and l-DOPA-induced dyskinetic behaviors.

ABSTRACT: A dynamic equilibrium between dopamine and acetylcholine (ACh) is essential for striatal circuitry and motor function, as imbalances are associated with Parkinson's disease (PD) and levodopa-induced dyskinesia (LID). Conventional theories posit that cholinergic signaling is pathologically elevated in PD as a result of increased ACh release, which contributes to motor deficits. However, using approaches to measure receptor-mediated signaling, we found that, rather than the predicted enhancement, the strength of cholinergic transmission at muscarinic M4 receptor synapses on direct pathway medium spiny neurons was decreased in dopamine-depleted mice. This adaptation was due to a reduced postsynaptic M4 receptor function, resulting from down-regulated receptors and downstream signaling. Restor

SUBMITTER: Nielsen BE 

PROVIDER: S-EPMC11578179 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature