SYNAPTIC MICROCIRCUITRY OF TYROSINE HYDROXYLASE-CONTAINING NEURONS AND TERMINALS IN THE STRIATUM OF MPTP-TREATED MONKEYS

摘要

A population of tyrosine hydroxylase (TH)-containing neurons that up-regulates after lesion of the nigrostriatal dopaminergic pathway has been described in the primate striatum. The goal of this study was to examine the morphology, synaptology and chemical phenotype of these neurons and TH-immunoreactive (TH-ir) terminals in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys. TH-ir perikarya were small (10-12 μm), displayed nuclear invaginations and received very few synaptic inputs. On the other hand, TH-containing dendrites were typically large in diameter (>1.0 μm) and received scarce synaptic innervation from putative excitatory and inhibitory terminals forming asymmetric and symmetric synapses, respectively. More than 70% of TH-positive intrastriatal cell bodies were found in the caudate nucleus and the pre-commissural putamen, considered as the associative functional territories of the primate striatum. Less then 10% of these cells displayed calretinin immunoreactivity. TH-immunoreactive terminals rarely formed clear synaptic contacts, except for a few that established asymmetric axo-dendritic synapses. Almost two thirds of TH-containing boutons displayed GABA immunoreactivity in the striatum of parkinsonian monkeys whereas less than 5% did so in the normal striatum.These findings provide a strong support for the existence of a population of putative catecholaminergic interneurons in the associative territory of the striatum in parkinsonian monkeys. Their sparse synaptic innervation raises interesting issues regarding synaptic and non-synaptic mechanisms involved in the regulation and integration of these neurons in the striatal microcircuitry. Finally, the co-expression of GABA in TH-positive terminals in the striatum of dopamine-depleted monkeys suggests dramatic neurochemical changes in the catecholaminergic modulation of striatal activity in Parkinson’s disease.