Synaptic innervation of midbrain dopaminergic neurons by glutamate-enriched terminals in the squirrel monkey

Abstract

The excitatory amino acid, glutamate, has long been thought to be a transmitter that plays a major role in the control of the firing pattern of midbrain dopaminergic neurons. The present study was aimed at elucidating the anatomical substrate that underlies the functional interaction between glutamatergic afferents and midbrain dopaminergic neurons in the squirrel monkey. To do this, we combined preembedding immunocytochemistry for tyrosine hydroxylase and calbindin D-28k with postembedding immunostaining for glutamate. On the basis of their ultrastructural features, three types (so-called types I, II, and III) of glutamate-enriched terminals were found to form asymmetric synapses with dendrites and perikarya of midbrain dopaminergic neurons. The type I terminals accounted for more than 70% of the total population of glutamate-enriched boutons in contact with dopaminergic cells in the dorsal and ventral tiers of the substantia nigra pars compacta as well as in the ventral tegmental area, whereas 5-20% of the glutamatergic synapses with 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 dopaminergic 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 populations of midbrain dopaminergic neurons displayed glutamate immunoreactivity. In conclusion, our findings provide the first evidence that glutamate-enriched terminals form synapses with midbrain dopaminergic neurons in primates. The fact that the proportion of glutamatergic boutons in contact with dopaminergic cells is higher in the ventral tegmental area than in the substantia nigra pars compacta suggests that the different groups of midbrain dopaminergic neurons are modulated differently by extrinsic glutamatergic afferents in primates.

Presynaptic Modulation of Spontaneous Inhibitory Postsynaptic Currents by Gamma-hydroxybutyrate in the Substantia Nigra Pars Compacta

“…The great majority of synapses on the dopaminergic neurons of the SNc are GABAergic . These inhibitory inputs arise from local interneurons as well as from other areas such as globus pallidus, striatum, and substantia nigra pars reticulata (Somogyi et al, 1981;Smith and Bolam, 1990;Smith et al, 1996;Chen and Rice, 2002). GABA exerts its action on dopaminergic neurons of the SNc through GABA A and GABA B receptors (Bunney et al, 1991;Hausser and Yung, 1994;Paladini et al, 1999).…”

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

“…Neurons of the substantia nigra are predominantly involved in the nigralstriatal motor circuits, whereas neurons from the VTA are involved in corticolimbic circuits, which include the nucleus accumbens and the PFC. Dopaminergic neurons in the substantia nigra and the VTA receive glutamatergic inputs (Carr et al, 1999;Carr & Sesack, 2000;Counihan et al, 1998;Gauchy et al, 1994;Smith et al, 1996), and gluta-mate stimulates dopaminergic activity (Meltzer et al, 1997). Conversely, the glutamate system is inhibited by dopamine and facilitated by the inhibition of D 2 receptors.…”

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

“…2 B, D). On the other hand, dendrites of SNc neurons are innervated much less by striatal terminals and often are devoid of synaptic contacts (Bolam and Smith, 1990;Smith et al, 1996) (Fig. 2 A, C).…”