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A cytoarchitectonic and chemoarchitectonic analysis of the dopamine cell groups in the substantia nigra, ventral tegmental area, and retrorubral field in the mouse

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Abstract

The three main dopamine cell groups of the brain are located in the substantia nigra (A9), ventral tegmental area (A10), and retrorubral field (A8). Several subdivisions of these cell groups have been identified in rats and humans but have not been well described in mice, despite the increasing use of mice in neurodegenerative models designed to selectively damage A9 dopamine neurons. The aim of this study was to determine whether typical subdivisions of these dopamine cell groups are present in mice. The dopamine neuron groups were analysed in 15 adult C57BL/6J mice by anatomically localising tyrosine hydroxylase (TH), dopamine transporter protein (DAT), calbindin, and the G-protein-activated inward rectifier potassium channel 2 (GIRK2) proteins. Measurements of the labeling intensity, neuronal morphology, and the proportion of neurons double-labeled with TH, DAT, calbindin, or GIRK2 were used to differentiate subregions. Coronal maps were prepared and reconstructed in 3D. The A8 cell group had the largest dopamine neurons. Five subregions of A9 were identified: the reticular part with few dopamine neurons, the larger dorsal and smaller ventral dopamine tiers, and the medial and lateral parts of A9. The latter has groups containing some calbindin-immunoreactive dopamine neurons. The greatest diversity of dopamine cell types was identified in the seven subregions of A10. The main dopamine cell groups in the mouse brain are similar in terms of diversity to those observed in rats and humans. These findings are relevant to models using mice to analyse the selective vulnerability of different types of dopamine neurons.

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Abbreviations

3n:

Oculomotor nerve

AU:

Arbitrary unit

CLi:

Caudal linear nucleus of the raphe

CLV:

Caudolateroventral region of A9

cp:

Cerebral peduncle

cSNC-SNR:

Caudal part of the substantia nigra pars compacta and pars reticulata

DAB:

3,3′-diaminobenzidine

DAPI:

4′-6-diamidino-2-phenylindole

DAT:

Dopamine transporter

DBH:

Dopamine β-hydroxylase

dmSNC:

Dorsomedial portion of the substantia nigra pars compacta

DR:

Dorsal raphe nucleus

fr:

Fasciculus retroflexus

GIRK2:

G-protein-activated inwardly rectifying potassium channel 2

IF:

Interfascicular nucleus

IP:

Interpeduncular nucleus

lSNC:

Lateral part of the substantia nigra pars compacta

ml:

Medial lemniscus

mlf:

Medial longitudinal fasciculus

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MT:

Medial terminal nucleus of the optic tract

mtg:

Mammillotegmental tract

ns:

Nigrostriatal bundle

PaP:

Parapeduncular nucleus

PBP:

Parabrachial pigmented nucleus

PIF:

Parainterfascicular nucleus

pm:

Principal mammillary tract

PN:

Paranigral nucleus

PSTh:

Parasubthalamic nucleus

RLi:

Rostral linear nucleus

RMD:

Rostromediodorsal region of A9

ROI:

Region of interest

RRF:

Retrorubral field

rSNC:

Rostral region of the substantia nigra pars compacta

scp:

Superior cerebellar peduncle

SN:

Substantia nigra

SNCD:

Substantia nigra compact part dorsal tier

SNCL:

Substantia nigra compact part lateral tier

SNCM:

Substantia nigra compact part medial tier

SNCV:

Substantia nigra compact part ventral tier

SNL:

Substantia nigra pars lateralis

SNR:

Substantia nigra reticular part

SP:

Substance P

TH:

Tyrosine hydroxylase

ts:

Tectospinal tract

VTA:

Ventral tegmental area

VTAR:

Ventral tegmental area rostral part

vtgx:

Ventral tegmental decussation

xscp:

Decussation of the superior cerebellar peduncle

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Acknowledgments

This project was supported by the Australian Research Council Thinking Systems Initiative (TS0669860) and Linkage Infrastructure Grant (#LE100100074). GP is an NHMRC (National Health & Medical Research Council) Australia Fellow (grant #568605) and GMH is a NHMRC Senior Principal Research Fellow (grant #630434).

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Yuan Yuan

    Present address: College of Biomedical Engineering, Capital Medical University, Beijing, 100069, China

Authors and Affiliations

  1. Neuroscience Research Australia, University of New South Wales, Sydney, NSW, 2031, Australia

    YuHong Fu, Glenda Halliday, Zoltán Rusznák, Charles Watson & George Paxinos

  2. School of Medical Science, University of New South Wales, Sydney, NSW, 2052, Australia

    Glenda Halliday & George Paxinos

  3. Faculty of Health Science, Curtin University, Perth, WA, 6845, Australia

    Charles Watson

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  1. YuHong Fu
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Correspondence to Charles Watson.

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Y. Fu and Y. Yuan have made an equal contribution to this paper.

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Fu, Y., Yuan, Y., Halliday, G. et al. A cytoarchitectonic and chemoarchitectonic analysis of the dopamine cell groups in the substantia nigra, ventral tegmental area, and retrorubral field in the mouse. Brain Struct Funct 217, 591–612 (2012). https://doi.org/10.1007/s00429-011-0349-2

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