They are organized in five parallel cortico-basal ganglia-thalamocortical circuits, including the sensorimotor, associative and limbic circuits. GP and STN are the two principal components of the indirect pathway in these circuits, with the STN considered as a driving force of the output structures of basal ganglia. Based on our recent data, it is likely that the changes recorded in GP after Mn intoxication are a consequence of 5-HT depletion, but not NE depletion. Indeed, selective depletion of 5-HT by pCPA administration resulted in the same decrease of the firing rate and increase in the proportion of irregular and bursty neurons in GP. However, DSP-4, which is selective for NE depletion did not alter by itself the firing rate or the pattern of GP neurons. Interestingly, and in contrast to GP, the changes observed in STN neurons after repeated Mn intoxication are likely to be due to NE depletion, but not to 5-HT depletion. Indeed, DSP-4 administration resulted in the same decrease of the firing rate and increase in the proportion of irregular neurons recorded in the STN. However, selective 5-HT depletion did not alter the firing rate nor the pattern of STN neurons. Besides, lead intoxication, which reduced the tissue contents of NE without affecting the 5-HT system, changed in a similar way the firing activity of STN neurons. In addition to the depletion of NE and 5-HT, we cannot exclude that the changes in the firing activity of GP and STN neurons can also be due to the accumulation of Mn in GP and STN. Neuroimaging studies have shown an accumulation of Mn in the basal ganglia in addition to the frontal and parietal cortex. From a pathophysiological point of view, the firing activity changes of GP neurons after Mn intoxication is nearly similar to those observed in the 6-OHDA rat model of Parkinson’s disease, although the origin is not the same. However, the changes in STN neuronal activity in Mn-intoxicated animals are different from those observed after 6-OHDA-induced DA depletion in the striatum. While 6-OHDA lesion induced a switch from regular to bursty pattern with oscillations, Mn intoxication induced a switch from regular to irregular pattern. Together, these findings provide a logical explanation to the evidence that Mn-induced motor and nonmotor deficits are not improved by L-Dopa therapy as it does in Parkinson’s disease. In conclusion, the present study provides evidence that manganese intoxication is associated with impaired neurotransmission of monoaminergic systems, which is at the origin of changes in basal ganglia neuronal activity and the manifestation of motor and non-motor deficits similar to those observed in atypical Parkinsonism. Iron is required at the active center of several important enzymes, including those involved in the tricarboxylic acid cycle, respiration, lipid metabolism, DNA replication and repair. Because of its ability to lose or gain a single electron.