SYNAPTIC INNERVATION OF MIDBRAIN DOPAMINERGIC-NEURONS BY GLUTAMATE-ENRICHED TERMINALS IN THE SQUIRREL-MONKEY

The excitatory amino acid, glutamate, has long been thought to be a tr ansmitter that plays a major role in the control of the firing pattern of midbrain dopaminergic neurons. The present study was aimed at eluc idating the anatomical substrate that underlies the functional interac tion between glutamatergic afferents and midbrain dopaminergic neurons in the squirrel monkey. To do this, we combined preembedding immunocy tochemistry for tyrosine hydroxylase and calbindin D-28k with postembe dding immunostaining for glutamate. On the basis of their ultrastructu ral features, three types (so-called types I, II, and III) of glutamat e-enriched terminals were found to form asymmetric synapses with dendr ites and perikarya of midbrain dopaminergic neurons. The type I termin als accounted for more than 70% of the total population of glutamate-e nriched boutons in contact with dopaminergic cells in the dorsal and v entral tiers of the substantia nigra pars compacta as well as in the v entral tegmental area, whereas 5-20% of the glutamatergic synapses wit h dopaminergic neurons involved the two other types of terminals. The major finding of our study is that the glutamate-enriched boutons were involved in 70% of the axodendritic synapses in the ventral tegmental area. In contrast, less than 40% of the boutons in contact with dopam inergic dendrites were immunoreactive for glutamate in the dorsal and ventral tiers of the substantia nigra pars compacta. Approximately 50% of the terminals in contact with the perikarya of the different popul ations of midbrain dopaminergic neurons displayed glutamate immunoreac tivity. In conclusion, our findings provide the first evidence that gl utamate-enriched terminals form synapses with midbrain dopaminergic ne urons in primates. The fact that the proportion of glutamatergic bouto ns in contact with dopaminergic cells is higher in the ventral tegment al area than in the substantia nigra pars compacta suggests that the d ifferent groups of midbrain dopaminergic neurons are modulated differe ntly by extrinsic glutamatergic afferents in primates. (C) 1996 Wiley- Liss, Inc.