In vitro identification and electrophysiological characterization of dopamine neurons in the ventral tegmental area
Open accessAbstract
Dopamine (DA) neurons in the ventral tegmental area (VTA) have been implicated in brain mechanisms related to motivation, reward, and drug addiction. Successful identification of these neurons in vitro has historically depended upon the expression of a hyperpolarization-activated current (I(h)) and immunohistochemical demonstration of the presence of tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis. Recent findings suggest that electrophysiological criteria may be insufficient for distinguishing DA neurons from non-DA neurons in the VTA. In this study, we sought to determine factors that could potentially account for the apparent discrepancies in the literature regarding DA neuron identification in the rodent brain slice preparation. We found that confirmed DA neurons from the lateral VTA generally displayed a larger amplitude I(h) relative to DA neurons located in the medial VTA. Measurement of a large amplitude I(h) (>100 pA) consistently indicated a dopaminergic phenotype, but non-dopamine neurons also can have I(h) current. The data also showed that immunohistochemical TH labeling of DA neurons can render false negative results after relatively long duration (>15 min) whole-cell patch clamp recordings. We conclude that whole-cell patch clamp recording in combination with immunohistochemical detection of TH expression can guarantee positive but not negative DA identification in the VTA.
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Dopaminergic (DA) neurons in the lateral VTA were identified using the following criteria: firing frequency 1-5 Hz and spike width >1 ms in cell-attached configuration, membrane capacitance >28 pF, and presence of an Ih current and a leak current >150 pA when hyperpolarized from −40 mV to −120 mV in 10 mV steps.
“Dopaminergic (DA) neurons in this area were identified evaluating the following features: 1) cells firing at a frequency of 1-5 Hz and the spike width > 1ms in cell attached configuration, 2) membrane capacitance (Cm) > 28 pF and 3) the presence of an Ih current and a leak current > 150 pA, when hyperpolarized from −40 mV to −120 in 10 mV steps (Bariselli et al., 2016; Zhang et al., 2010).”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Zhang et al., 2010
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- Authors
- Zhang, T. A., Placzek, A. N., & Dani, J. A.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Dani, John A.
- ORCID
- Dani, John A.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 59
- Issue
- 6
- Pages
- 431-436
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC2946471
- OpenAlex
- W2076492877
- Cited by
- 100
- References
- 44
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 10 · 2012: 5
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Diana Helis Henry Medical Research Foundation
- National Institute on Drug Abuse (R01DA009411)
- National Institute of Neurological Disorders and Stroke (R01NS021229)
- 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, ventral tegmental area, hyperpolarization-activated current, tyrosine hydroxylase, neuronal identification, whole-cell patch clamp, immunohistochemistry, non-dopaminergic neurons, brain slices
- MeSH terms
- Action Potentials, Analysis of Variance, Animals, Dopamine, Electrophysiology, Immunohistochemistry, Mice, Transgenic, Neurons, Tyrosine 3-Monooxygenase, Ventral Tegmental Area, Reverse Transcriptase Polymerase Chain Reaction, Mice
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