Functional properties of dopamine neurons and co-expression of vasoactive intestinal polypeptide in the dorsal raphe nucleus and ventro-lateral periaqueductal grey
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The dorsal raphe nucleus (DRN) and ventrolateral periaqueductal grey (vlPAG) regions contain populations of dopamine neurons, often considered to be a dorsal caudal extension of the A10 group [mostly found in the ventral tegmental area (VTA)]. Recent studies suggest they are involved in promoting wakefulness and mediate some of the antinociceptive and rewarding properties of opiates. However, little is known about their electrophysiological properties. To address this, we used Pitx3-GFP and tyrosine hydroxylase (TH)-GFP mice to carry out targeted whole-cell recordings from this population in acute brain slices. We found that DRN/vlPAG dopamine neurons have characteristics similar to most VTA dopamine neurons, but distinct from dorsal raphe serotonin neurons. They fire broad action potentials at a relatively slow, regular rate, exhibit a hyperpolarization-activated inward current and delayed repolarization, and show spike-frequency adaptation in response to prolonged depolarization. In addition, they receive fast excitatory and inhibitory synaptic inputs. Moreover, we found co-expression of vasoactive intestinal polypeptide in small, periaqueductal dopamine neurons, but generally not in larger, more ventral dopamine neurons.
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Vip+ dopamine neurons are the most caudally located population, found in the periaqueductal gray and dorsal raphe, where they account for about 49% of dopamine neurons, but are sparser in the ventral tegmental area.
“Vip+ DA neurons are the most caudally located population”
From Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches (2020) · cites this paper as [46]
TH+ DRN neurons express AADC and DAT.
“The TH+ DRN neurons have been confirmed as DAergic as they express aromatic L-amino decarboxylase (AADC), the enzyme that catalyzes conversion of L-3,4-dihydroxyphenylalanine, the product of TH, to DA (Lu et al., 2006) and the DA transporter (DAT) (Dougalis et al., 2012).”
From Dorsal raphe dopamine neurons represent the experience of social isolation (2016) · cites this paper as Dougalis et al., 2012
The neuropeptide vasoactive intestinal peptide (VIP) is co-expressed in a subset of DA neurons.
“the neuropeptide vasoactive intestinal peptide (VIP) is co-expressed in a subset of DA neurons (Dougalis et al., 2012).”
From Dorsal raphe dopamine neurons represent the experience of social isolation (2016) · cites this paper as Dougalis et al., 2012
Vip was found in all 3 DA neuron subtypes, as previously reported for DRN and CLi DA neurons, but Vip expression varied between the 3 subtypes.
“Although Vip was found in all 3 DA neuron subtypes, as previously reported for DRN and CLi DA neurons (Dougalis et al., 2012; Poulin et al., 2018; Poulin et al., 2014), Vip expression varied between the 3 subtypes.”
From Molecular and anatomical organization of the dorsal raphe nucleus (2019) · cites this paper as Dougalis et al., 2012
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- Authors
- Dougalis, A. G., Matthews, G. A. C., Bishop, M. W., Brischoux, F., Kobayashi, K., & Ungless, M. A.
- Affiliations
- Hammersmith Hospital (GB)
- Centre National de la Recherche Scientifique (FR)
- Fukushima Medical University (JP)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2012-08-26
- Volume
- 36
- Issue
- 10
- Pages
- 3322-3332
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC4273537
- OpenAlex
- W2119641401
- Cited by
- 81
- References
- 56
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 11 · 2022: 5 · 2021: 7 · 2020: 2 · 2019: 8 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 3 · 2013: 2
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Strathclyde
- Japan Society for the Promotion of Science (23300119)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopaminergic neurons, dorsal raphe nucleus, vasoactive intestinal peptide, ventral tegmental area, electrophysiological properties, hyperpolarization-activated current, spike frequency adaptation, synaptic input, wakefulness, antinociception, opioid reward
- MeSH terms
- Action Potentials, Animals, Mice, Inbred C57BL, Periaqueductal Gray, Raphe Nuclei, Transcription Factors, Tyrosine 3-Monooxygenase, Vasoactive Intestinal Peptide, Gene Expression, Homeodomain Proteins, Green Fluorescent Proteins, Mice, Synaptic Potentials, Dopaminergic Neurons, Serotonergic Neurons
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