Microstimulation-Induced Inhibition of Neuronal Firing in Human Globus Pallidus

TLDR

Neurosurgical treatment of Parkinson's disease frequently uses chronic high‑frequency deep brain stimulation in the internal globus pallidus to reduce dyskinesias and bradykinesia, but the underlying mechanisms remain unknown. This study examined how microstimulation in the GPi affects the firing of nearby neurons. Recordings were obtained from GPi using two microelectrodes spaced approximately 250–>600 µm apart in patients undergoing stereotactic exploration to localize the optimal lesion or DBS site. Microstimulation at currents <10 µA (0.15‑ms pulses at 5 Hz) inhibited the spontaneous activity of 22/23 GPi neurons, with inhibition lasting 10–25 ms at threshold, suggesting that stimulation preferentially activates axon terminals of striatal or external pallidal neurons, releasing GABA and inhibiting GPi neurons.

Abstract

Neurosurgical treatment of Parkinson's disease (PD) frequently employs chronic high-frequency deep brain stimulation (DBS) within the internal segment of globus pallidus (GPi) and can very effectively reduce L-dopa–induced dyskinesias and bradykinesia, but the mechanisms are unknown. The present study examined the effects of microstimulation in GPi on the activity of neurons close to the stimulation site. Recordings were made from GPi using two fixed or independently controlled microelectrodes, with the electrode tips usually ∼250 or >600 μm apart in PD patients undergoing stereotactic exploration to localize the optimal site for placement of a lesion or DBS electrode. The spontaneous activity of nearly all of the cells (22/23) recorded in GPi in three patients was inhibited by microstimulation at currents typically <10 μA (0.15-ms pulses at 5 Hz). The inhibition had a duration of 10–25 ms at threshold. These findings suggest that microstimulation within GPi preferentially excites the axon terminals of striatal and/or external pallidal neurons causing release of GABA and inhibition of GPi neurons.