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.