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

Kelly, E. A.; Contreras, J.; Duan, A.; Vassell, R.; Fudge, J. L.

doi:10.1101/2022.02.08.479596

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bioRxiv · 10.1101/2022.02.08.479596

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

Kelly, E. A.·Contreras, J.·Duan, A.·Vassell, R.·Fudge, J. L.

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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. HIGHLIGHTSO_LIThe A10 subregion expands laterally and caudally in nonhuman primates C_LIO_LIThe A10, A9, and A8 comprise 52%, 42% and 6% of DA neurons, respectively C_LIO_LIGABAergic neurons are more evenly dispersed across subregions C_LIO_LIThe A8 subpopulation has the highest ratio of GABA: DA neurons C_LI

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Kelly, E. A., Contreras, J., Duan, A., Vassell, R., Fudge, J. L.. 2022-02-10. Unbiased stereologic estimates of dopaminergic and GABAergic neurons in the A10, A9, and A8 subpopulations in the young male Macaque. https://doi.org/10.1101/2022.02.08.479596

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