Selective vulnerability of pallidal neurons in the early phases of manganese intoxication

Prolonged exposure to manganese in mammals may cause an extrapyramidal diso rder characterized by dystonia and rigidity. Gliosis in the pallidal segmen ts underlies the well-established phase of the intoxication. The early phas e of the intoxication may be characterized by psychic, nonmotor signs, and its morphological and electrophysiological correlates are less defined. In a rat model of manganese intoxication (20 mg/ml in drinking water for 3 mon ths), neither neuronal loss nor gliosis was detected in globus pallidus (GP ). However, a striking vulnerability of manganese-treated GP neurons emerge d. The majority of GP neurons isolated from manganese-treated rats died fol lowing brief incubation in standard dissociation media. In addition, patch- clamp recordings in the whole-cell configuration were not tolerated by surv iving GP neurons. Neither coeval but untreated GP neurons nor striatal ones manifested analogous susceptibility. Using the perforated-patch mode of re cording we attempted at identifying the functional hallmarks of GP vulnerab ility: in particular, voltage-gated calcium currents and glutamate-induced currents were examined. Manganese-treated GP neurons exhibited calcium curr ents similar to control cells aside from a slight reduction in the dihydrop yridine-sensitive current facilitation. Strikingly, manganese-treated GP ce lls - but not striatal ones - manifested peculiar responses to glutamate, s ince repeated applications of the excitatory amino acid, at concentrations which commonly promote desensitizing responses, produced instead an irrever sible cell damage. Possible mechanisms are discussed.