Efferent synaptic connections of dopaminergic neurons grafted into the caudate nucleus of experimentally induced parkinsonian monkeys are different from those of control animals.
This study investigated the question of whether grafted dopamine cells in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys form synapses and, if they do, whether their postsynaptic targets were the same as those in control monkeys or in previous studies in rats. Electron-microscopic single immunostaining was performed for tyrosine hydroxylase on vibratome sections prepared from the head of the caudate nucleus of controls and MPTP-treated African green monkeys (Cercopithecus aethiops sabaeus) that received a graft. Furthermore, correlated light- and electron-microscopic double immunostaining was carried out for tyrosine hydroxylase and calbindin in the same brain area of MPTP-treated plus grafted animals. In control monkeys, the majority (97%) of dopamine boutons terminate on spines that were also synaptic targets of immunonegative boutons forming asymmetric synaptic contacts: synaptic triads. In MPTP-treated, grafted animals, the majority of transplanted dopamine cells terminate on dendritic shafts (67%) and somata (32%), and only a few (1.33%) form axospine synapses. The results of the double immunostaining experiments indicated that these newly formed axosomatic and axodendritic synapses are associated with calbindin-immunoreactive, medium-sized, spiny striatonigral projection neurons. These observations indicate that: (1) dopamine from transplanted embryonic tissue acts via synaptic contacts on host neurons; (2) the primary synaptic targets of transplanted dopamine cells are not spines but dendrites and somata of host neurons; (3) these target neurons are the same as in control animals; and (4) comparing these observations with results of control and grafted rats, there are major species differences between rats and monkeys in the dopamine innervation of both control and transplanted animals.
Leranth
C
C
Department of Obstetrics and Gynecology, Yale University, School of Medicine, New Haven, CT 06520-8063, USA. csaba.leranth@yale.edu
Sladek
J R
JR
Roth
R H
RH
Redmond
D E
DE
D000818:Animals; D064026:Calbindins; D002421:Caudate Nucleus / Q000601:surgery*; D002522:Chlorocebus aethiops; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000633:toxicity; D004525:Efferent Pathways / Q000187:drug effects; D020267:MPTP Poisoning; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000637:transplantation; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000601:surgery; D051381:Rats; D012016:Reference Values; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D013045:Species Specificity; D013569:Synapses / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D064026:Calbindins; D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine