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Elevated potassium provides an ionic mechanism for deep brain stimulation in the hemiparkinsonian rat
Author(s) -
Sutton Alexander C.,
Yu Wilson,
Calos Megan E.,
Mueller Lauren E.,
Berk Matthew,
Shim Jenny,
Molho Eric S.,
Brotchie Jonathan M.,
Carlen Peter L.,
Shin Damian S.
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12040
Subject(s) - subthalamic nucleus , stimulation , deep brain stimulation , forelimb , neuroscience , premovement neuronal activity , basal ganglia , chemistry , electrophysiology , parkinson's disease , in vivo , medicine , endocrinology , psychology , biology , central nervous system , microbiology and biotechnology , disease
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 m m , 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 m m KC l injection into the substantia nigra pars reticulata ( SN r) or the subthalamic nucleus. In the SN r, neuronal spiking activity decreased from 38.2 ± 1.2 to 14.6 ± 1.6 Hz and attenuated SN r 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 m m KC l onto SN r neurons in vitro caused a depolarisation block and sustained quiescence of SN r activity. In conclusion, our data showed that elevated K + injection into the hemiparkinsonian rat SN r improved forelimb akinesia, which coincided with a decrease in SN r neuronal spiking activity and desynchronised activity in SN r 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 .