Synaptische Plastizität in Pallidum bei Dystoniepatienten

Aberrant forms of synaptic plasticity may underlie the pathophysiology of dystonia, a movement disorder characterized by sustained muscle contractions and abnormal postures. The internal segment of the globus pallidus (GPi) is the primary somatomotor output of the basal ganglia and tonically inhibits corticothalamic and brainstem premotor circuits. The remarkable efficacy of GPi high frequency stimulation (HFS) for surgical therapy of dystonia suggests that aberrant plasticity at the output of basal ganglia may be involved. Synaptic plasticity in GPi was induced by HFS in awake patients with generalized (whole body) and cervical (neck only) dystonia. Dual microelectrode wide band (5–5kHz) recordings were made in 2 cervical and 2 generalized dystonia patients undergoing implantation of deep brain stimulation electrodes in the GPi. Evoked field potentials (eFPs) were recorded while stimulating with single pulses (50uA, 0.3ms biphasic pulses, 1Hz) from the second electrode located about 1mm away at the same dorsoventral level. After establishing a stable baseline, standard tetanizing HFS (100Hz, 2s trains repeated 4 times at 10s) was performed and the effects on eFP amplitudes were measured for up to 5 minutes. Then low frequency stimulation (LFS, 20uA, 2–5Hz, 10–20s) was given through the recording electrode to test for post-synaptic depression of the eFP amplitudes. A final HFS confirmed the range of bi-directional plasticity. HFS potentiated eFPs by similar degrees in both groups (gen. by 65%, cer. by 71%), while LFS depressed eFPs in generalized dystonia to a much greater extent than in cervical dystonia (eFP amplitude ranges of 106% and 19% respectively). The final HFS potentiated both groups to pre-LFS levels. Patients with cervical and generalized dystonia demonstrate similar induction but different reversal of plasticity, indicating an asymmetric bi-directional plasticity in GPi neurons. These preliminary results suggest that more severe forms of dystonia are associated with greater post-synaptic depression of GPi neuronal responsiveness.