Dopamine across timescales and cell types: Relevance for phenotypes in Parkinson's disease progression

Jillian L Seiler; Xiaowen Zhuang; Alexandra B Nelson; Talia N Lerner

doi:10.1016/j.expneurol.2024.114693

Dopamine across timescales and cell types: Relevance for phenotypes in Parkinson's disease progression

Exp Neurol. 2024 Apr:374:114693. doi: 10.1016/j.expneurol.2024.114693. Epub 2024 Jan 17.

Authors

Jillian L Seiler¹, Xiaowen Zhuang², Alexandra B Nelson³, Talia N Lerner⁴

Affiliations

¹ Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
² Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California San Francisco, San Francisco, CA, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
³ Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA, USA; Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California San Francisco, San Francisco, CA, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA. Electronic address: alexandra.nelson@ucsf.edu.
⁴ Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Northwestern University Interdepartmental Neuroscience Program (NUIN), Evanston, IL, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA. Electronic address: talia.lerner@northwestern.edu.

PMID: 38242300
DOI: 10.1016/j.expneurol.2024.114693

Abstract

Dopamine neurons in the substantia nigra pars compacta (SNc) synthesize and release dopamine, a critical neurotransmitter for movement and learning. SNc dopamine neurons degenerate in Parkinson's Disease (PD), causing a host of motor and non-motor symptoms. Here, we review recent conceptual advances in our basic understanding of the dopamine system - including our rapidly advancing knowledge of dopamine neuron heterogeneity - with special attention to their importance for understanding PD. In PD patients, dopamine neuron degeneration progresses from lateral SNc to medial SNc, suggesting clinically relevant heterogeneity in dopamine neurons. With technical advances in dopamine system interrogation, we can understand the relevance of this heterogeneity for PD progression and harness it to develop new treatments.

Keywords: Cell types; Dopamine; Heterogeneity; L-DOPA; Movement disorders; Neurodegeneration; Parkinson's disease; Striatum; Substantia nigra pars compacta.

Publication types

Review

MeSH terms

Disease Progression
Dopamine*
Dopaminergic Neurons
Humans
Parkinson Disease* / genetics
Phenotype
Substantia Nigra

Substances

Dopamine