On the properties of identified dopaminergic neurons in the mouse substantia nigra and ventral tegmental area
Abstract
Abstract We studied the properties of dopaminergic neurons in the substantia nigra pars compacta ( SN pc) and ventral tegmental area ( VTA ) in mice expressing the enhanced green fluorescent protein ( eGFP ) under the control of the tyrosine hydroxylase promoter ( TH ‐ GFP ). By using a practical map of cell positioning in distinct SN pc and VTA subregions in horizontal midbrain slices we saw that the spontaneous firing, membrane properties, cell body size and magnitude of the hyperpolarization‐activated current ( I h ) in TH ‐ GFP ‐positive neurons ( TH ‐ GFP + ) vary significantly among subregions, following a mediolateral gradient. Block of I h with Zd7288 inhibited firing in the most lateral subregions, but had little effect in the intermediate/medial VTA . In addition, TH ‐ GFP + cells were excited by Met 5 ‐Enkephalin. Extracellular recordings from a large neuron number showed that all TH ‐ GFP + cells were inhibited by dopamine, suggesting that this is a reliable approach for identifying dopaminergic neurons in vitro . Simultaneous recordings from dopamine‐sensitive and dopamine‐insensitive neurons showed that dopamine‐insensitive cells (putative non‐dopaminergic neurons) are unaffected by Zd7288 but inhibited by Met 5 ‐Enkephalin. Under patch‐clamp, dopamine generated a quantitatively similar outward current in most TH ‐ GFP + neurons, although medial VTA cells showed reduced dopamine sensitivity. Pargyline prolonged the dopamine current, whereas cocaine enhanced dopamine‐mediated responses in both the SN pc and the VTA . Our work provides new insights into the variability in mouse midbrain dopaminergic neurons along the medial–lateral axis and points to the necessity of a combination of different electrophysiological and pharmacological approaches for reliably identifying these cells to distinguish them from non‐dopaminergic neurons in the midbrain.
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DA neurons show differences in size along the medio-lateral axis, with the smallest neurons in the intermediate region and the largest in the lateral part.
“DA neurons are not only functionally heterogeneous, but also show differences in size along the medio-lateral axis, such that the smallest neurons are located within the intermediate region, and the largest neurons in the lateral part (Krashia et al., 2017).”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Krashia et al., 2017
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Nobili, A., Latagliata, E. C., Viscomi, M. T., Cavallucci, V., Cutuli, D., Giacovazzo, G., Krashia, P., Rizzo, F. R., Marino, R., Federici, M., et al. (2017) · Nature Communications · doi:10.1038/ncomms14727 · Cited by 514 · see citing works
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“After polymerization, chips from the intermediate VTA (Krashia et al., 2017; Morales and Margolis, 2017) were cut from the wafers, glued to blank resin blocks and sectioned with an ultramicrotome.”
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- Authors
- Krashia, P., Martini, A., Nobili, A., Aversa, D., D'Amelio, M., Berretta, N., Guatteo, E., & Mercuri, N. B.
- Affiliations
- University of Rome Tor Vergata (IT)
- Università Campus Bio-Medico (IT)
- Department of Experimental Neurology IRCCS Santa Lucia Foundation Via del Fosso di Fiorano 64 00143 Rome Italy
- Fondazione Santa Lucia (IT)
- Parthenope University of Naples (IT)
- Corresponding author
- Mercuri, Nicola Biagio
- ORCID
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2016-09-11
- Volume
- 45
- Issue
- 1
- Pages
- 92-105
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2513128864
- Cited by
- 61
- References
- 54
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 4 · 2020: 7 · 2019: 11 · 2018: 7 · 2017: 3
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- CINECA IRIS Institutial research information system (Parthenope University of Naples) (submittedVersion)
- Funders
- Italian Health Ministry (GR-2011-02351457)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- dopaminergic neurons, substantia nigra pars compacta, ventral tegmental area, tyrosine hydroxylase promoter, enhanced green fluorescent protein, hyperpolarization-activated current, ZD7288, met-enkephalin, dopamine sensitivity, pargyline, cocaine, non-dopaminergic neurons
- MeSH terms
- Animals, Cells, Cultured, Dopamine, Female, Male, Membrane Potentials, Mesencephalon, Substantia Nigra, Tyrosine 3-Monooxygenase, Ventral Tegmental Area, Mice, Dopaminergic Neurons
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