STEREOLOGICAL ESTIMATES OF DOPAMINERGIC, GABAERGIC AND GLUTAMATERGIC NEURONS IN THE VENTRAL TEGMENTAL AREA, SUBSTANTIA NIGRA AND RETRORUBRAL FIELD IN THE RAT

By R. Nair‐Roberts, S. D. Chatelain-Badie, E. Benson, H. White-Cooper, J. Bolam, Mark A. Ungless. Neuroscience, 2008

620 citations recorded by the source corpus.

Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental area whose function remains unclear. Although dopamine neurons have been intensively studied and quantified, there is little quantitative information regarding the GABAergic and glutamatergic neurons. We therefore used unbiased stereological methods to estimate the number of dopaminergic, GABAergic and glutamatergic cells in these regions in the rat. Neurons were identified using a combination of immunohistochemistry (tyrosine hydroxylase) and in situ hybridization (glutamic acid decarboxylase mRNA and vesicular glutamate transporter 2 mRNA). In substantia nigra pars compacta 29% of cells were glutamic acid decarboxylase mRNA-positive, 58% in the retrorubral field and 35% in the ventral tegmental area. There were further differences in the relative sizes of the GABAergic populations in subnuclei of the ventral tegmental area. Thus, glutamic acid decarboxylase mRNA-positive neurons represented 12% of cells in the interfascicular nucleus, 30% in the parabrachial nucleus, and 45% in the parainterfascicular nucleus. Vesicular glutamate transporter 2 mRNA-positive neurons were present in the ventral tegmental area, but not substantia nigra or retrorubral field. They were mainly confined to the rostro-medial region of the ventral tegmental area, and represented approximately 2-3% of the total neurons counted (∼1600 cells). These results demonstrate that GABAergic and glutamatergic neurons represent large proportions of the neurons in what are traditionally considered as dopamine nuclei and that there are considerable heterogeneities in the proportions of cell types in the different dopaminergic midbrain regions.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/e13c01dd4e7c87e8d5a4e157bf8eb2d5d9b1d868

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Malenka
2. Wolfram Schultz
3. S. Lammel
4. Anthony A. Grace
5. S. Sesack
6. K. Tye
7. B. Lim
8. Garret D. Stuber

In Cognitive Neuroscience

1. R. Malenka
2. S. Lammel
3. S. Sesack
4. Anthony A. Grace
5. B. Lim
6. K. Tye
7. Garret D. Stuber
8. Jana L Phillips

Citations in the corpus

• Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli (2009, background): “We and others have described a discrete population of putatively glutamatergic neurons concentrated in the rostral VTA, which may represent these TH-negative neurons (20, 21).”
• Cortico-Basal Ganglia Reward Network: Microcircuitry (2009, positive): “Non-DA neurons in the ventral midbrain are primarily GABAergic and make up approximately 30–35% of the cells in the VTA (Swanson, 1982; Mugnaini and Oertel, 1985; Steffensen et al, 1998; Nair-Roberts et al, 2008).”
• A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice (2018, background): “As recent breakthroughs in single-cell sequencing have highlighted a previously unrecognized molecular, morphological, physiological, and functional heterogeneity of DANs (Nair-Roberts et al., 2008; Ungless and Grace, 2012), we expected that the targeted expression of genetically encoded GRABDA sens”
• Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement (2011, positive): “…and complex population of neurons (Margolis et al., 2006; Fields et al., 2007; Dobi et al., 2010; Lammel et al., 2008; Histed et al., 2009; Nair-Roberts et al., 2008; Swanson, 1982) and fails to elicit reliable DA release in well-trained animals (Garris et al., 1999; OwessonWhite et al.,…”
• Neuron-type specific signals for reward and punishment in the ventral tegmental area (2012, background): “Dopaminergic neurons make up about 55–65% of VTA neurons; the rest are mostly GABAergic inhibitory neuron”
• Reward and aversion in a heterogeneous midbrain dopamine system (2013, background): “In the late 1980s and early 1990s using in vitro slice recordings researchers began to classify DA neurons as principal (mostly DAergic) and secondary (GABAergic) (Grace & Onn, 1989; Johnson & North, 1992) on the basis of distinct physiological and pharmacological properties as well as tyrosine hydr”
• Activation of VTA GABA neurons disrupts reward consumption (2012, positive): “(Margolis et al., 2006; Nair-Roberts et al., 2008; Swanson, 1982; Yamaguchi et al., 2011), that may act in concert to orchestrate reward-seeking behavior.”