Modifications of precentral cortex discharge and EMG activity in monkeys with MPTP-induced lesions of DA nigral neurons.

1. Individual neurons were recorded extracellularly in the precentral forelimb area of two monkeys trained to perform rapid, large amplitude flexion and extension movements of the contralateral forearm in response to auditory signals. Electromyographic (EMG) activity in the biceps/triceps muscles was recorded separately under the same conditions. The dopaminergic (DA) neurons of the substantia nigra (SN) were destroyed selectively by repeated series of intravenous injections of MPTP. The lesion was verified on serial slices using both tyrosine hydroxylase immunocytochemistry and classical staining methods. 2. In normal monkeys, the frequency of firing of precentral neurons shows rapid changes shortly before the onset of displacement. In our sample (n = 102), most of the neurons (49%) tested during movement in both directions (flexion, extension) showed a reciprocal pattern of activity for the two directions of movement, a small percentage (19%) exhibited a change for only one direction (unidirectional neurons), and the remaining 32% displayed a similar change for both directions of movement (bidirectional neurons). 3. In MPTP-treated monkeys, movement-related modification of neuronal activity was more gradual, beginning earlier and lasting longer relative to the onset of movement. The cellular reaction time (the time between the auditory cue and a significant change in neuronal activity) was not significantly altered. Spontaneous firing of precentral neurons (n = 124) did not increase significantly, and the dynamic discharge rate was unchanged after the nigral lesion. However, only 18% of cortical neurons still presented a reciprocal pattern of discharge for the two directions of movement, while the percentage of unidirectional neurons increased (50%), and the percentage of bidirectional neurons remained the same (32%). 4. After MPTP treatment, alterations in movement parameters and EMG activity were observed. Mean reaction time and movement duration increased by 20-25% and 25-30% respectively. The movements were slower and were associated with a generalized depression in the shape and the amplitude of EMG activity in the agonist muscle. 5. The neuronal basis for the observed central and peripheral disturbance in the MPTP-treated monkeys is discussed. We conclude that SN lesion leads to two main disturbances of cortical activity: i) the loss of the reciprocal pattern of response of movement-related cortical cells, and ii) an inability of the motor cortex to modify its activity in response to peripheral input.