Homeostatic regulation of dopaminergic neurons without dopamine

摘要

An astonishing number of psy-chomotor disorders stem from alterations of the function of brain neurons that release or respond to the neurotransmitter dopamine. Synthesized from the amino acid tyrosine, dopamine is implicated in drug abuse, attention deficit hyperactivity disorder, Tourette's syndrome, dystonia, schizophrenia, and Parkinson's disease (PD), where the control of internally generated movement or thought is disturbed. In PD, dopaminergic neurons in a region of the mesencephalon, the substantia nigra pars compacta, stop releasing dopamine and eventually die, leading to the emergence of bradykine-sia, tremor, and rigidity. The neural adaptations in target structures, like the striatum, that accompany the gradual loss of dopaminergic neurons and the symptoms of the disease are beginning to be understood. But what happens to the dopaminergic neurons that remain? How do they respond to falling levels of dopamine? The prevailing view is that dopamine release and the activity of dopaminergic neurons is controlled by homeostatic mechanisms. That is, activity is regulated to maintain an optimal basal level of dopamine in target structures by feedback mechanisms that sense dopamine. The work by Robinson et al. (4) in this issue of PNAS challenges the completeness of this view.