Neuroleptics given chronically to rats induce behavioral sequelae which mimic tardive dyskinesia in some respects. The intent of this study was to investigate the ultrastructural correlates of oral dyskinesias (vacuous chewing movements [VCMs]), induced by chronic haloperidol treatment. After 6 months of treatment, rats were divided into low or high VCM groups. Rats in the high VCM group were either sacrificed on drug or were withdrawn from drug for 4 weeks. Ultrastructural analyses of the striatum indicated that synaptic density: 1) was significantly decreased in both the low and high VCM groups compared to normal controls; 2) was more profoundly decreased in the high VCM group as compared to the low VCM group; and 3) recovered to normal following drug withdrawal. Compared to controls, the density of asymmetric synapses was reduced by a similar magnitude in both the low and high VCM groups, suggesting that this change is a result of haloperidol treatment and independent of VCMs. Conversely, the density of symmetric synapses was reduced compared to normal, only in the high VCM group, suggesting that this change is specifically related to the expression of VCMs. In addition, mitochondrial profiles were hypertrophied and less frequent in the high VCM group in comparison to controls; size, but not number, recovered following drug withdrawal. These results identify distinct ultrastructural correlates of chronic haloperidol treatment that are unique to rats that develop VCMs and suggest that these ultrastructural features may play a role in the pathophysiology of oral dyskinesias in rats.

The goal of this study was to characterize the synaptic organization of the normal human adult striatum for comparison with other species and with the diseased human striatum. Samples of striatal tissue from the Maryland Brain Collection obtained at autopsy with postmortem intervals of less than 4 hours were prepared for electron microscopic analysis according to standard techniques. The caudate nucleus and the putamen were similar in terms of the proportions of synaptic subtypes, the lengths of synaptic subtypes, and the area of most types of axon terminals. The proportions of major striatal synaptic subdivisions, such as axospinous synapses (83.5%) and asymmetric synapses (77.5%), were similar to that of the monkey (82% and 77%, respectively) but slightly lower than found in the rat (90% and 89%, respectively). Interestingly, the proportion of synapses with perforated postsynaptic densities (23%), a type of synapse thought to represent synaptic plasticity, was much higher in humans than in rats (5-8%). The lengths of asymmetric synapses (0.697 micron) were significantly longer than that of symmetric synapses (0.423 microns), a relationship found in other mammals. Also, the areas of terminals forming asymmetric synapses (0.707 micron2) were larger than those forming symmetric synapses (0.401 micron2), also consistent with data from other species. The length of axospinous synapses (0.656 micron) and the area of the terminals forming them (0.611 micron2) were not significantly different from the length of axodendritic synapses (0.523 micron) or the area of terminals forming them (0.602 micron2). This study is the first quantitative study on synaptic organization in human postmortem striatum. The results indicate that the synaptic organization of the human striatum is similar, but not identical, to that of other mammalian species.

The goal of this study was to characterize the synaptic organization of the normal human adult striatum for comparison with other species and with the diseased human striatum. Samples of striatal tissue from the Maryland Brain Collection obtained at autopsy with postmortem intervals of less than 4 hours were prepared for electron microscopic analysis according to standard techniques. The caudate nucleus and the putamen were similar in terms of the proportions of synaptic subtypes, the lengths of synaptic subtypes, and the area of most types of axon terminals. The proportions of major striatal synaptic subdivisions, such as axospinous synapses (83.5%) and asymmetric synapses (77.5%), were similar to that of the monkey (82% and 77%, respectively) but slightly lower than found in the rat (90% and 89%, respectively). Interestingly, the proportion of synapses with perforated postsynaptic densities (23%), a type of synapse thought to represent synaptic plasticity, was much higher in humans than in rats (5-8%). The lengths of asymmetric synapses (0.697 micron) were significantly longer than that of symmetric synapses (0.423 microns), a relationship found in other mammals. Also, the areas of terminals forming asymmetric synapses (0.707 micron2) were larger than those forming symmetric synapses (0.401 micron2), also consistent with data from other species. The length of axospinous synapses (0.656 micron) and the area of the terminals forming them (0.611 micron2) were not significantly different from the length of axodendritic synapses (0.523 micron) or the area of terminals forming them (0.602 micron2). This study is the first quantitative study on synaptic organization in human postmortem striatum. The results indicate that the synaptic organization of the human striatum is similar, but not identical, to that of other mammalian species.

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