Age-related neuronal loss from the substantia nigra-pars compacta and ventral tegmental area of the rhesus monkey.

This study was undertaken to document the effect of age on the volume, number, and size of neurons in the substantia nigra pars compacta (SNpc), the paranigral (VTApn), and the parabrachial pigmentosus (VTApbp) nuclei of the VTA in behaviorally well-characterized rhesus monkeys. Using a point counting technique and unbiased stereological methods, we found no significant effects of age on the volume of these dopaminergic brain stem nuclei, but there was significant age-related loss of total number of neurons in the SNpc and VTApn. The loss of neurons in the SNpc was found to be greater for neurons measuring less than 200 microm2 in cross sectional area, a size corresponding to the small GABAergic neurons in this nucleus. Age-related loss of total number of neurons in the SNpc and VTApn showed significant correlations with impairment on the delay phase of the delayed non match to sample test (DNMS), in the VTApn with impaired performance on the delayed recognition span test (DRST), and in the SNpc with impaired performance on the spatial component of reversal tasks. These correlations suggest that the loss of neurons in the SNpc and VTApn in these old monkeys may contribute to these behavioral deficits.