Dopaminergic Neurons  - Development and Stem Cells

Functions and Anatomical Structure of the Dopaminergic Neurons:

Dopaminergic neurons in the brain exist in the ventral mesencephalon, caudal diencephalic periaquaductal gray and hypothalamic regions.   The neurons in each region differ markedly in function and molecular characteristics.

The dopaminergic neurons in the ventral mesencephalon originate in the floor and basal plates of the mesencephalon and caudal diencephalon and are therefore called 'mesodiencephalic dopaminergic (mdDA) neurons'. They are mainly located in two groups:

1. The 'A9' group neurons, which are located in the substantia nigra pars compacta (SNC). These neurons send their axons to the dorsal striatum (caudate and putamen) and thus form the 'nigro-striatal pathway'.  The SNC dopaminergic neurons are involved in control of voluntary movement and are severely affected in Parkinson's disease.
2. The 'A10' group neurons are located in the ventral tegmental area (VTA) and send their axons to the ventral striatum (nucleus accumbens) and the limbic cortex (forming the ‘meso-limbic’ pahway ) and the prefrontal cortex (forming the 'meso-cortical' pathway). The VTA dopaminergic neurons are involved in regulation of emotion-related behavior and are affected in depression and schizophrenia.

Embryonic and Postnatal Development of the Dopaminergic Neurons

Meso-diencephalic dopaminergic precursor cells proliferate in the ventricular zone of the floor and basal plates of the mesencephalon and the caudal diencephalon (prosomers 1,2,3).  It is postulated that the cells that finally reside in the SNC originate from the diencephalic basal plate, while the VTA dopaminergic neurons originate from the mesencephalic floor plate.

Following signals from the isthmus organizer (IsO, at the midbrain-hindbrain border) and the floor plate, the precursor cells differentiate into dopaminergic progenitor cells. This process occurs during their migration from the ventricular zone, along radial glia towards their final destinations in the tegmental mantle layer.

Mature embryonic dopaminergic neurons residing  in the SNC and VTA send their growth cones towards the telencephalon.  At the embryonic stage, VTA and SNC dopaminergic neurons project unselectively to the striatum and cortex. The refinement of fibers to form the 'nigro-striatal' and 'meso-limbic' pathways only occurs post-natally.