Molecular basis for catecholaminergic neuron diversity
Open accessAbstract
Catecholaminergic neurons control diverse cognitive, motor, and endocrine functions and are associated with multiple psychiatric and neurodegenerative disorders. We present global gene-expression profiles that define the four major classes of dopaminergic (DA) and noradrenergic neurons in the brain. Hypothalamic DA neurons and noradrenergic neurons in the locus coeruleus display distinct group-specific signatures of transporters, channels, transcription, plasticity, axon-guidance, and survival factors. In contrast, the transcriptomes of midbrain DA neurons of the substantia nigra and the ventral tegmental area are closely related with <1% of differentially expressed genes. Transcripts implicated in neural plasticity and survival are enriched in ventral tegmental area neurons, consistent with their role in schizophrenia and addiction and their decreased vulnerability in Parkinson's disease. The molecular profiles presented provide a basis for understanding the common and population-specific properties of catecholaminergic neurons and will facilitate the development of selective drugs.
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Bulk profiling experiments comparing substantia nigra pars compacta and ventral tegmental area neurons yielded gene expression differences but could not distinguish heterogeneous populations within each anatomical cluster.
“Bulk profiling experiments comparing SNc and VTA neurons did indeed yield some interesting gene expression differences [6–9], but suffered from the caveat that they could not distinguish heterogeneous populations within each anatomical cluster.”
From Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches (2020) · cites this paper as [6]
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- Authors
- Grimm, J., Mueller, A., Hefti, F., & Rosenthal, A.
- Affiliations
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-09-07
- Volume
- 101
- Issue
- 38
- Pages
- 13891-13896
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC518849
- OpenAlex
- W2131058184
- Cited by
- 150
- References
- 55
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 15 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 4 · 2017: 10 · 2016: 10 · 2015: 8 · 2014: 14 · 2013: 8 · 2012: 7
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- catecholaminergic neurons, dopaminergic neurons, noradrenergic neurons, neuronal heterogeneity, gene expression profiling, locus coeruleus, substantia nigra, ventral tegmental area, midbrain dopaminergic neurons, neuroplasticity, axon guidance, schizophrenia, addiction, Parkinson's disease
- MeSH terms
- Animals, Catecholamines, Female, Gene Amplification, Hydrogen Peroxide, Neurons, RNA, Rats, Sprague-Dawley, In Situ Hybridization, Pyramidal Cells, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Rats
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