Ontogeny of Dopaminergic Neurons

DOPAMINE IN THE ADULT CNS The developmental functions mediated by dopaminergic signaling are not currently fully appreciated, however, more is known about the influences of DA in the mature brain. Synthesis of DA involves conversion of the amino acid L-tyrosine into L-dopa by the rate-limiting enzyme tyrosine hydroxylase (TH). Subsequent activity of DOPA decarboxylase results in final conversion to DA. DA is widely distributed in the CNS with important projections into the forebrain. The nigrostriatal tract consists of DA neurons with cell bodies located in the substantia nigra (SN) pars compacta and axonal processes terminating in the dorsal striatum. The striatum is a component of the extrapyramidal motor system and plays an essential role in the coordination of locomotor activity. The mesocorticolimbic pathway is another major forebrain dopaminergic projection. This pathway arises in the midbrain ventral tegmental area (VTA) and provides input to the nucleus accumbens, and some limbic regions including limbic cortical regions (medial prefrontal (mPFC) and anterior cingulate cortex (ACC)). These pathways are those important for mediating behaviors associated with motivation, reward (endogenous systems and drug abuse) and reinforcement, as well as cognitive and executive functions including attention .