Abstract
High-frequency stimulation (HFS) in the globus pallidus is used to ameliorate clinical symptoms of Parkinson's disease, dystonia, and other disorders. Previous in vivo studies have shown diverse static effects of stimulation on discharge rates and firing patterns of neurons along the corticobasal ganglia loop. In vitro studies, together with other experimental and theoretical studies, have suggested the involvement of synaptic plasticity in stimulation effects. To explore the effects of HFS on synaptic transmission, we studied the dynamic changes in neuronal activity in vivo, using multielectrode recordings during stimulation in the globus pallidus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates. Stimulation effects evolved over time and were pronounced during the first 10 s of stimulation, where 69% of the 249 recorded neurons changed their firing rate and 61% displayed time-locked firing. The time-locked response faded away in 43% of the responding neurons, and its pattern was altered in the remaining cells: the peak response shifted away in time from the stimulus onset, and its amplitude decreased. Repetition of the stimulation protocol revealed a full resetting of the effect, implying short-term synaptic depression. This evolving response is indicative of the transient plasticity of the corticobasal ganglia network in vivo during HFS. Therefore, short-term depression of synaptic transmission may contribute to the mechanism underlying the effects of stimulation during the resulting steady state, altering the balance of neuronal interactions and interfering with pathological information transmission.