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Unformatted text preview: Abstract. Dopaminergic neurons in the mammalian brain have received substantial attention in the past given their fundamental role in several body functions and behaviours. The largest dopaminergic population is found in two nuclei of the ventral midbrain. Cells of the substantia nigra pars compacta are involved in the control of voluntary move- ments and postural reflexes, and their degeneration in the adult brain leads to Parkinsons disease. Cells of the ventral tegmental area modulate rewarding and cognitive behav- Cell. Mol. Life Sci. 63 (2006) 187206 1420-682X/06/020187-20 DOI 10.1007/s00018-005-5387-6 Birkhuser Verlag, Basel, 2006 iours, and their dysfunction is involved in the pathogenesis of addictive disorders and schizophrenia. Because of their clinical relevance, the embryonic development and main- tenance of the midbrain dopaminergic cell groups in the adult have been intensively studied in recent years. In the present review, we provide an overview of the mechanisms and factors involved in the development of dopaminergic neurons in the mammalian brain, with a special emphasis on the midbrain dopaminergic population. Key words. Development; dopamine; neuron; midbrain; forebrain; substantia nigra; ventral tegmental area. Introduction Localization and function of dopaminergic neurons in the adult mammalian brain Dopamine (DA) is one of the catecholaminergic neuro- transmitters of the vertebrate central nervous system (CNS), where it is synthesized in a common biosynthetic pathway as a precursor to noradrenaline and adrenaline. Tyrosine hydroxylase (Th) is the first and rate-limiting en- zyme in this pathway that converts the essential amino acid tyrosine to L-dihydroxy-phenylalanine (L-DOPA). L- DOPA is then decarboxylated by the enzyme L-aromatic amino acid decarboxylase (Aadc/Ddc) to produce dop- amine. Expression of Th has therefore been widely used as a molecular marker for DA-synthesizing (or dopaminergic, DA) neurons. Much attention has been paid in recent years to the population of DA neurons in the mammalian brain given their pivotal role in the control and modulation of motor and endocrine functions, and affective and cognitive behaviours. The cell bodies of these neurons are found in stereotypic positions within the mammalian brain, as listed below from caudal to rostral (fig. 1): 1) DA neurons of the ventral midbrain (mesencephalon) are arranged in two distinct nuclei: the substantia ni- gra pars compacta (SNc) and the ventral tegmental area (VTA); and in the retrorubral field (RrF). Histor- ically, these DA cell groups were designated A8 (RrF), A9 (SNc) and A10 (VTA) . In the rat brain, the midbrain dopaminergic (mDA) cell group is made up of around 45,000 neurons, whereas in the human brain, it consists of approximately 590,000 neurons in the first four decades of life ....
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