Synaptic contacts in schizophrenia: studies using immunocytochemical identification of dopaminergic neurons

Immunocytochemical identification of dopaminergic neurons was performed using an immunoperoxidase method employing antibodies to tyrosine hydroxylase. The ultrastructure of synaptic contacts on dopaminergic (tyrosine hydroxylase immunopositive (TP) cells) neurons was investigated in the substantia nigra in the brains of four patients with schizophrenia and three mentally healthy subjects (controls). The substantia nigra of schizophrenia patients differed from control material in showing the following changes in the ultrastructure of presynaptic terminals contacting TP neurons: reductions in the size of terminals with dense matrix and poorly distinguished vesicles; swelling of terminals with small numbers of vesicles displaced from the active zone of the synapse; hyperplasia of mitochondria in some presynaptic boutons; appearance of membranous lamellar structures within or adjacent to presynaptic boutons. These changes to terminals were located mostly on the distal (small and intermediate) TP dendrites in the compact zone of the substantia nigra, where nearly all the dendrites detected belonged to dopaminergic neurons and the altered terminals formed asymmetrical contacts with short active zones. In the reticular part of the substantia nigra of schizophrenic patients, changes in the ultrastructure of presynaptic terminals were relatively rare; altered terminals contacted both tyrosine hydroxylase immunopositive as well as with the tyrosine hydroxylase immunonegative dendrites located in this structure.