Light microscopic autoradiography was used to identify cells in the neostriatum that became labelled after the local injection of [3H]gamma-aminobutyrate (GABA). The GABA-accumulating cells comprised up to 15% of the total population of neurons. Thirty-seven of these cells were examined in the electron microscope and it was found that they all had similar cytological characteristics, i.e., prominent nuclear indentations, a moderate volume of cytoplasm, rich in organelles, and sparse synaptic input to the perikaryon. Nine of the cells that had accumulated GABA were also impregnated following Golgi staining. These Golgi-impregnated neurons were of medium size and all had dendrites that were aspiny, often varicose, and that occasionally followed a recurving path. After gold toning, the Golgi-impregnated, GABA-accumulating neurons were examined in the electron microscope and were found to receive boutons forming symmetrical or asymmetrical synaptic contacts on their somata and dendrites; the symmetrical synapses were most common on the cell body and proximal dendrites, while the distal dendrites mainly received boutons forming asymmetrical contacts. We conclude that one type of GABAergic neuron in the neostriatum is a type of medium-sized aspiny neuron and that this neuron is likely to receive synaptic input both from neurons within the striatum and from neurons in distant brain regions. We suggest that this neuron is a local circuit neuron in the neostriatum since its morphological features are quite distinct from those of identified projecting neurons.

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Human fetal mesencephalic dopamine (DA) neurons, obtained from 6.5-9 week old aborted fetuses, were grafted to the striatum of immunosuppressed rats with 6-hydroxydopamine lesions of the ascending mesostriatal DA pathway. The effects on amphetamine-induced motor asymmetry were studied at various timepoints after grafting. At eight weeks, functional graft effects were not evident but after 11 weeks small effects on motor asymmetry could be monitored and rats tested 19-21 weeks after grafting exhibited full reversal of the lesion-induced rotational behaviour. Four rats were sacrificed at different timepoints between 8 and 20 weeks and the grafted DA neurons were studied in tyrosine hydroxylase (TH) immunocytochemically stained sections at the light and electronmicroscopic level. The grafts contained a total of 500-700 TH-positive neurons in each rat. In one rat sacrificed 8 weeks after grafting the grafted neurons were TH-positive but exhibited virtually no fiber outgrowth. In another rat, sacrificed after 11 weeks, a sparse TH-positive fiber plexus was seen to extend into the adjacent host neostriatum. Two rats sacrificed after 20 weeks both contained TH-positive neurons that gave rise to a rich fiber network throughout the entire host neostriatum, and this fiber network was also seen to extend into the globus pallidus and nucleus accumbens. Very coarse TH-positive processes, identified as dendrites in the electron microscope, projected up to 1.5-2.0 mm from the graft into the host striatum. Ultrastructural analysis revealed that the grafted neurons had formed no TH-positive synaptic contacts with host striatal neurons after 8 weeks, and at 11 weeks some few TH-positive synapses were identified. Twenty weeks after transplantation, abundant TH-positive synaptic contacts with host neurons were seen throughout the neostriatum, and such contacts were identified in the globus pallidus as well. Thus, the present study provides tentative evidence for a time-link between the development of synaptic contacts and the appearance of functional graft effects. Similar to the normal mesostriatal DA pathway, ingrowing TH-positive axons formed symmetric synapses and were mainly seen to contact dendritic shafts and spines. However, in comparison to the normal rat striatum there was a higher incidence of TH-immunoreactive boutons forming synapses onto neuronal perikarya. The TH-positive dendrites that extended into the host striatum were seen to receive non-TH-immunoreactive synaptic contacts, presumably arising from the host neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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