Heterogeneous dopamine populations project to specific subregions of the primate amygdala.

Amygdala dysfunction has been reported among patients with various psychiatric disorders, and dopamine is critical to the amygdala's ability to mediate fear conditioning. Recent work indicates that the midbrain dopaminergic neurons have heterogeneous receptor and membrane channel profiles, as well as differential physiologic responses to discrete stimuli. To begin understanding how dopamine affects amygdala physiology and pathology in higher primates, we mapped the inputs from the midbrain dopaminergic neurons to various amygdala nuclei in the monkey using retrograde and anterograde tracing techniques, and single and double immunofluorescence histochemistry for tracer and tyrosine hydroxylase, a dopamine marker. Our results show that the primate amygdala as a whole receives broad input, mostly from the dorsal tier of the substantia nigra, pars compacta, and the A8-retrorubral field. Input from the A10-ventral tegmental area, while present, was less prominent. These results differ from data in the rat, where the midline A10-ventral tegmental area is a major source of dopamine to the amygdala "mesolimbic" pathway. Both the "amygdala proper" and the "extended amygdala" receive the majority of their input from the dorsal tier of the substantia nigra and A8-retrorubral field, but the extended amygdala receives additional modest input from the ventral tier. In addition, the "extended amygdala" structures have a denser input than the "amygdala proper," with the exception of the lateral core of the central nucleus, which receives no input. Our anterograde studies confirm these findings, and revealed fine, diffuse terminal fibers in the amygdala proper, but a denser network of fibers in the extended amygdala outside the lateral core of the central nucleus. These results indicate that the entire extent of the dorsal tier beyond the A10-ventral tegmental area may regulate the amygdala in primates, and subsequently serve as a source of dysfunction in primate psychopathology.