Journal of Neuroscience, Vol 5, 603-616, Copyright © 1985 by Society for Neuroscience
Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study
TF Freund, JP Bolam, A Bjorklund, U Stenevi, SB Dunnett, JF Powell and AD Smith
In adult rats with a unilateral 6-hydroxydopamine-induced destruction of
the nigrostriatal dopamine (DA) pathway, grafts of embryonic substantia
nigra can establish a new dopaminergic terminal fiber plexus in the
previously denervated neostriatum and compensate for some of the behavioral
deficits induced by the nigrostriatal lesion. In the present study the
synaptic connections of the ingrowing DA fibers from the graft were
analyzed ultrastructurally, using immunocytochemical localization of
tyrosine hydroxylase (TH), in animals whose lesion- induced motor asymmetry
had been completely compensated for by the nigral grafts. In two of the
animals, horseradish peroxidase-wheatgerm agglutinin conjugate was injected
into the graft in order to trace possible reciprocal afferent connections
to the graft from the host striatum. TH-immunoreactive axons from the graft
were seen to make abundant symmetric synapses with neuronal elements in the
host neostriatum. Between 85 and 90% of these synapses were on dendritic
shafts and spines, and the rest were on neuronal perikarya. Two principal
targets were identified: dendrites of spiny neurons, the majority of which
are likely to be striatal projection neurons; and the cell bodies of giant
neurons, most (or perhaps all) of which are known to be cholinergic
interneurons. The synapses made on dendritic spines, which constituted
about 40% of all TH-positive synapses formed by the TH-positive neurons in
the graft, resembled those seen in normal animals, both in that they made
contacts with spine necks and in that they invariably were associated with
an asymmetric TH-negative synapse contacting the spine head. The
innervation of the giant cell perikarya, which constituted about 6% of all
TH-positive synapses found, was strikingly abnormal in that the
graft-derived TH-positive fibers formed dense pericellular "baskets"
selectively around the giant cell bodies. Such arrangements were never seen
in the normal striatum, nor did they occur in the intact contralateral
striatum in the grafted animals. It is proposed that this apparent
dopaminergic hyperinnervation from the graft could provide a powerful
inhibition of the cholinergic interneurons in the reinnervated host
striatum, and that such an inhibitory mechanism could assist in the
graft-induced functional recovery by potentiating the functional effects of
DA synapses terminating on the spiny efferent neurons. This dual
innervation may thus help to explain why restoration of only a small
proportion of the striatal DA innervation by the graft is sufficient to
induce complete compensation of, e.g., motor asymmetry in the lesioned
rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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