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Striatal synaptic adaptations in Parkinson's disease.
Shen, Weixing; Zhai, Shenyu; Surmeier, D James.
Afiliação
  • Shen W; Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States of America.
  • Zhai S; Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States of America.
  • Surmeier DJ; Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States of America. Electronic address: j-surmeier@northwestern.edu.
Neurobiol Dis ; 167: 105686, 2022 06 01.
Article em En | MEDLINE | ID: mdl-35272023
ABSTRACT
The striatum is densely innervated by mesencephalic dopaminergic neurons that modulate acquisition and vigor of goal-directed actions and habits. This innervation is progressively lost in Parkinson's disease (PD), contributing to the defining movement deficits of the disease. Although boosting dopaminergic signaling with levodopa early in the course of the disease alleviates these deficits, later this strategy leads to the emergence of debilitating dyskinesia. Here, recent advances in our understanding of how striatal cells and circuits adapt to this progressive de-innervation and to levodopa therapy are discussed. First, we discuss how dopamine (DA) depletion triggers cell type-specific, homeostatic changes in spiny projection neurons (SPNs) that tend to normalize striatal activity but also lead to disruption of the synaptic architecture sculpted by experience. Second, we discuss the roles played by cholinergic and nitric oxide-releasing interneurons in these adaptations. Third, we examine recent work in freely moving mice suggesting that alterations in the spatiotemporal dynamics of striatal ensembles contributes to PD movement deficits. Lastly, we discuss recently published evidence from a progressive model of PD suggesting that contrary to the classical model, striatal pathway imbalance is necessary but not sufficient to produce frank parkinsonism.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article