Elevated potassium provides an ionic mechanism for deep brain stimulation in the hemiparkinsonian rat

Alexander C. Sutton, Wilson Yu, Megan E. Calos, Lauren E. Mueller, Matthew Berk, Jenny Shim, Eric S. Molho, Jonathan M. Brotchie, Peter L. Carlen, Damian S. Shin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The mechanism of high-frequency stimulation used in deep brain stimulation (DBS) for Parkinson's disease (PD) has not been completely elucidated. Previously, high-frequency stimulation of the rat entopeduncular nucleus, a basal ganglia output nucleus, elicited an increase in [K+]e to 18 mm, in vitro. In this study, we assessed whether elevated K+ can elicit DBS-like therapeutic effects in hemiparkinsonian rats by employing the limb-use asymmetry test and the self-adjusting stepping test. We then identified how these effects were meditated with in-vivo and in-vitro electrophysiology. Forelimb akinesia improved in hemiparkinsonian rats undergoing both tests after 20 mm KCl injection into the substantia nigra pars reticulata (SNr) or the subthalamic nucleus. In the SNr, neuronal spiking activity decreased from 38.2 ± 1.2 to 14.6 ± 1.6 Hz and attenuated SNr beta-frequency (12-30 Hz) oscillations after K+ treatment. These oscillations are commonly associated with akinesia/bradykinesia in patients with PD and animal models of PD. Pressure ejection of 20 mm KCl onto SNr neurons in vitro caused a depolarisation block and sustained quiescence of SNr activity. In conclusion, our data showed that elevated K+ injection into the hemiparkinsonian rat SNr improved forelimb akinesia, which coincided with a decrease in SNr neuronal spiking activity and desynchronised activity in SNr beta frequency, and subsequently an overall increase in ventral medial thalamic neuronal activity. Moreover, these findings also suggest that elevated K+ may provide an ionic mechanism that can contribute to the therapeutic effects of DBS for the motor treatment of advanced PD.

Original languageEnglish (US)
Pages (from-to)231-241
Number of pages11
JournalEuropean Journal of Neuroscience
Volume37
Issue number2
DOIs
StatePublished - Jan 2013

Keywords

  • 6-hydroxydopamine rat model
  • K
  • Parkinson's disease
  • Substantia nigra pars reticulata

Fingerprint Dive into the research topics of 'Elevated potassium provides an ionic mechanism for deep brain stimulation in the hemiparkinsonian rat'. Together they form a unique fingerprint.

Cite this