Adaptive changes in striatal projection neurons explain the long duration response and the emergence of dyskinesias in patients with Parkinson's disease

Publikation: Beitrag in FachzeitschriftÜbersichtsartikel (Review)BeigetragenBegutachtung

Abstract

Neuronal activity in the brain is tightly regulated. During operation in real time, for instance, feedback and feedforward loops limit excessive excitation. In addition, cell autonomous processes ensure that neurons' average activity is restored to a setpoint in response to chronic perturbations. These processes are summarized as homeostatic plasticity (Turrigiano in Cold Spring Harb Perspect Biol 4:a005736-a005736, 2012). In the basal ganglia, information is mainly transmitted through disinhibition, which already constraints the possible range of neuronal activity. When this tightly adjusted system is challenged by the chronic decline in dopaminergic neurotransmission in Parkinson's disease (PD), homeostatic plasticity aims to compensate for this perturbation. We here summarize recent experimental work from animals demonstrating that striatal projection neurons adapt excitability and morphology in response to chronic dopamine depletion and substitution. We relate these cellular processes to clinical observations in patients with PD that cannot be explained by the classical model of basal ganglia function. These include the long duration response to dopaminergic medication that takes weeks to develop and days to wear off. Moreover, dyskinesias are considered signs of excessive dopaminergic neurotransmission in Parkinson's disease, but they are typically more severe on the body side that is more strongly affected by dopamine depletion. We hypothesize that these clinical observations can be explained by homeostatic plasticity in the basal ganglia, suggesting that plastic changes in response to chronic dopamine depletion and substitution need to be incorporated into models of basal ganglia function. In addition, better understanding the molecular mechanism of homeostatic plasticity might offer new treatment options to avoid motor complications in patients with PD.

Details

OriginalspracheEnglisch
Seiten (von - bis)497-503
Seitenumfang7
FachzeitschriftJournal of neural transmission
Jahrgang129
Ausgabenummer5-6
PublikationsstatusVeröffentlicht - Juni 2022
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC9188504
Scopus 85129888545
ORCID /0000-0002-2387-526X/work/150328951

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Dyskinesias, Homeostatic plasticity, Medium spiny neurons, Parkinson’s disease, Spiny projection neurons, Striatum

Bibliotheksschlagworte