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Unbiased stereological estimates of dopaminergic and GABAergic neurons in the A10, A9, and A8 subregions in the young male Macaque

View ORCID ProfileEmily A. Kelly, Jancy Contreras, Annie Duan, Rochelle Vassell, View ORCID ProfileJulie L. Fudge
doi: https://doi.org/10.1101/2022.02.08.479596
Emily A. Kelly
1Department of Neuroscience, University of Rochester Medical Center
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Jancy Contreras
2Department of Neuroscience, The City University of New York
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Annie Duan
1Department of Neuroscience, University of Rochester Medical Center
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Rochelle Vassell
1Department of Neuroscience, University of Rochester Medical Center
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Julie L. Fudge
1Department of Neuroscience, University of Rochester Medical Center
3Department of Psychiatry, University of Rochester Medical Center
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  • ORCID record for Julie L. Fudge
  • For correspondence: Julie_fudge@urmc.rochester.edu
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ABSTRACT

The ventral midbrain is the primary source of dopamine- (DA) expressing neurons in most species. GABA-ergic and glutamatergic cell populations are intermixed among DA-expressing cells and purported to regulate both local and long-range dopamine neuron activity. Most work has been conducted in rodent models, however due to evolutionary expansion of the ventral midbrain in primates, the increased size and complexity of DA subpopulations warrants further investigation. Here, we quantified the number of DA neurons, and their GABA-ergic complement in classic DA cell groups A10 (midline ventral tegmental area nuclei [VTA] and parabrachial pigmented nucleus [PBP]), A9 (substantia nigra, pars compacta [SNc]) and A8 (retrorubral field [RRF]) in the macaque. Because the PBP is a disproportionately expanded feature of the A10 group, and has unique connectional features in monkeys, we analyzed A10 data by dividing it into ‘classic’ midline nuclei and the PBP. Unbiased stereology revealed total putative DA neuron counts to be 210,238 +/− 17,127 (A10 = 110,319 +/− 9,649, A9= 87,399 +/−7,751 and A8=12,520 +/− 827). Putative GABAergic neurons were fewer overall, and evenly dispersed across the DA subpopulations (GAD67= 71,215 +/− 5,663; A10=16,836 +/− 2,743; A9=24,855 +/− 3,144 and A8=12,633 +/− 3,557). Calculating the GAD67/TH ratio for each subregion revealed differential balances of these two cell types across the DA subregions. The A8 subregion had the highest complement of GAD67-positive neurons compared to TH-positive neurons (1:1), suggesting a potentially high capacity for GABAergic inhibition of DA output in this region.

HIGHLIGHTS

  • The A10 subregion expands laterally and caudally in nonhuman primates

  • The A10, A9, and A8 comprise 52%, 42% and 6% of DA neurons, respectively

  • GABAergic neurons are more evenly dispersed across subregions

  • The A8 subpopulation has the highest ratio of GABA: DA neurons

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Methods section updated with more detail; Most figures and tables updated to clarify; original tables 5 and 6 combined; new table 6.

  • ABBREVIATIONS

    CaBP
    calcium binding protein D28k
    CLi
    caudal linear nucleus
    DA
    dopamine
    III
    third nerve root
    GABA
    Gamma-Aminobutyric Acid
    GAD67
    glutamic acid decarboxylase 67
    Glu
    Glutamate
    IF
    intrafascicular nucleus
    IP
    interpeduncular nucleus
    PBP
    parabrachial pigmented nucleus
    PN
    paranigral nucleus
    RN
    red nucleus
    RRF
    retrorubral field
    RMTg
    rostromedial tegmental nucleus
    scp
    decussation of the superior cerebellar peduncle
    SN
    substantia nigra
    SNc
    substantia nigra, pars compacta
    SNr
    substantia nigra, pars reticulata
    STN
    subthalamic nucleus
    TH
    tyrosine hydroxylase
    VTA
    ventral tegmental area.
  • Copyright 
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    Posted May 26, 2022.
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    Unbiased stereological estimates of dopaminergic and GABAergic neurons in the A10, A9, and A8 subregions in the young male Macaque
    Emily A. Kelly, Jancy Contreras, Annie Duan, Rochelle Vassell, Julie L. Fudge
    bioRxiv 2022.02.08.479596; doi: https://doi.org/10.1101/2022.02.08.479596
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    Unbiased stereological estimates of dopaminergic and GABAergic neurons in the A10, A9, and A8 subregions in the young male Macaque
    Emily A. Kelly, Jancy Contreras, Annie Duan, Rochelle Vassell, Julie L. Fudge
    bioRxiv 2022.02.08.479596; doi: https://doi.org/10.1101/2022.02.08.479596

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