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All About Parkinson's Disease

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Single-cell labeling studies

These studies showed that virtually all components of primate basal ganglia and associated thalamic nuclei, including the striatum, external (GPe) and internal (GPi) segments of globus pallidus, subthalamic nucleus (STN), centre median/parafascicular thalamic complex (CM-Pf), and substantia nigra (SN), harbor several types of projection neurons endowed with a long, widespread and highly branched axon. The most extreme example is GPi neurons, the axon of which arborizes profusely within the thalamus and brainstem (Fig. 1). Despite their relatively small cell body (about 30 mm in diameter), these neurons support an axon of about 30 cm long. Hence, the cell body/axon length ratio is such a case is of about 1 /10,000. Single-cell labeling studies have also provided the first clear picture of the complexity of the axonal arborization of single DA neurons of the SNc in both rodents and primates. The data revealed that, irrespective of their location in the ventral or dorsal tiers of the SNc, DA nigral neurons project to either the strio-somes (patches) or the extrastrisomal com partments of the striatum by means of a long and highly arborized axon. The pattern of axonal arborization varies markedly from one neuron to the other. Some axons arborizes profusely in a large sector of the striatum, but provide very few axon collateral to extra-striatal structures, such as the pallidal complex and STN, whereas other axons branched profusely in non-striatal structures but provide only a few thin collaterals to the stria-tum. These two types of axons appear to represent the two extremes of a widespread morphological continuum that contains many intermediate or mixed forms of axonal arborizations. Or data suggest that the pattern of axonal arborization of nigrofugal DA neurons obeys a simple rule, that is, the more the axon arborizes in the striatum the less it does so in non-striatal structures, and vice versa.

Parkinsonian monkeys

Observations in PD monkeys have revealed that nigrostriatal DA neurons aborizing profusely in the striatum are much more vulnerable to degeneration than nigral neurons with an axon that branches abundantly in non-striatal structures and relatively little in the striatum. In accordance with neuroanato-mical findings described above, the data obtained in PD monkeys indicate that the nigrostriatal DA system is composed of several subsystems, each having its specific origin in the SNc, its particular terminal region in the striatum and its own degree of vulnerability to neurodegenerative processes that are at play in PD. The most highly vulnerable neurons are those whose cell body is located in the ventral tiers portion of the SNc and whose axon arborizes principally in the sen-sorimotor territory of the striatum. These are the DA neurons that contains neuromelanin pigments and which are known to degenerate massively in sporadic PD. Much less sensitive to degeneration are the DA neurons with a cell body in the ventral tegmental areas whose axon arborizes principally in the ven-

Fig. 1. Axonal arborization of a GPi neuron that projects to the ventral tier thalamic nuclei, centre median/parafascicular thalamic complex, pedunculopontine tegmental nucleus, Forel's field H, zona incerta and retrorubral area, as viewed on sagittal plane. The number of axonal varicosities observed in each target site is indicated in parentheses, whereas the arrow points the location of the cell body. The axon was entirely reconstructed from serial sections using camera lucida drawings and a computerized image-analysis system. CM centre median thalamic nucleus; FH Forel field H; GPi internal segment of the globus pallidus; Pf paraf-ascicular thalamic nucleus; PPN pedunculopontine tegmental nucleus; RRA retrorubral area; VA/VL ventral anterior/ventral lateral thalamic nuclei; VM ventromedial thalamic nucleus

Fig. 1. Axonal arborization of a GPi neuron that projects to the ventral tier thalamic nuclei, centre median/parafascicular thalamic complex, pedunculopontine tegmental nucleus, Forel's field H, zona incerta and retrorubral area, as viewed on sagittal plane. The number of axonal varicosities observed in each target site is indicated in parentheses, whereas the arrow points the location of the cell body. The axon was entirely reconstructed from serial sections using camera lucida drawings and a computerized image-analysis system. CM centre median thalamic nucleus; FH Forel field H; GPi internal segment of the globus pallidus; Pf paraf-ascicular thalamic nucleus; PPN pedunculopontine tegmental nucleus; RRA retrorubral area; VA/VL ventral anterior/ventral lateral thalamic nuclei; VM ventromedial thalamic nucleus tral (limbic) territory of the striatum. Also less sensitive to degeneration are the DA neurons that project directly to GPi and much less so to striatum. The latter neurons, as well as those at the origin of the mesolimbic dopaminergic pathway, express calbindin, a calcium-binding protein that maintains in-tracellular calcium homeostasis and which may thus confer some resistance against neu-rodegenerative processes.

Huntington's disease

The pathological hallmark of HD is a gross atrophy of the striatum, which is the result of a massive neuronal loss of the striatal medium spiny projection neurons. Our observations indicate that, in contrast to medium-sized spiny projection neurons, virtually all the large and medium-sized aspiny local circuit neurons of the striatum are spared in HD.

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