Glutamatergic inputs to midbrain dopaminergic neurons in primates

Anterograde tract-tracing and immunohistochemical methods were used to stud y projections from the pedunculopontine tegmental nucleus (PPN) to midbrain dopaminergic neurons in the squirrel monkey (Saimiri sciureus). The PPN ha rbored numerous cholinergic and glutamatergic neurons, as well as neurons t hat displayed both cholinergic and glutamatergic markers. Injections of ant erograde tracer into the PPN led to intense fiber labeling in the substanti a ni,ora pars compacta (SNc) and the ventral tegmental area (VTA). This ped unculonigral projection was partly bilateral. At the electron microscopic l evel, about 40-60% of the anterogradely labeled terminal boutons were gluta mate-positive and formed asymmetric synapses with the dopaminergic neurons of the SNc-VTA complex. These data provide direct evidence for a pedunculon igral glutamatergic projection. This projection may play a crucial role in the control of the firing pattern of SNc-VTA dopaminergic neurons and could be involved in glutamate-mediated excitotoxicity that is believed to lead to SNc cell death in Parkinson's disease. (C) 1999 Elsevier Science Ltd. Al l rights reserved.