RT Journal Article
SR Electronic
T1 Patterned, But Not Tonic, Optogenetic Stimulation in Motor Thalamus Improves Reaching in Acute Drug-Induced Parkinsonian Rats
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1211
OP 1216
DO 10.1523/JNEUROSCI.3277-14.2015
VO 35
IS 3
A1 Sonja Seeger-Armbruster
A1 Clémentine Bosch-Bouju
A1 Shane T.C. Little
A1 Roseanna A. Smither
A1 Stephanie M. Hughes
A1 Brian I. Hyland
A1 Louise C. Parr-Brownlie
YR 2015
UL http://www.jneurosci.org/content/35/3/1211.abstract
AB High-frequency deep brain stimulation (DBS) in motor thalamus (Mthal) ameliorates tremor but not akinesia in Parkinson's disease. The aim of this study was to investigate whether there are effective methods of Mthal stimulation to treat akinesia. Glutamatergic Mthal neurons, transduced with channelrhodopsin-2 by injection of lentiviral vector (Lenti.CaMKII.hChR2(H134R).mCherry), were selectively stimulated with blue light (473 nm) via a chronically implanted fiber-optic probe. Rats performed a reach-to-grasp task in either acute drug-induced parkinsonian akinesia (0.03–0.07 mg/kg haloperidol, s.c.) or control (vehicle injection) conditions, and the number of reaches was recorded for 5 min before, during, and after stimulation. We compared the effect of DBS using complex physiological patterns previously recorded in the Mthal of a control rat during reaching or exploring behavior, with tonic DBS delivering the same number of stimuli per second (rate-control 6.2 or 1.8 Hz, respectively) and with stimulation patterns commonly used in other brain regions to treat neurological conditions (tonic 130 Hz, theta burst (TBS), and tonic 15 Hz rate-control for TBS). Control rats typically executed >150 reaches per 5 min, which was unaffected by any of the stimulation patterns. Acute parkinsonian rats executed <20 reaches, displaying marked akinesia, which was significantly improved by stimulating with the physiological reaching pattern or TBS (both p < 0.05), whereas the exploring and all tonic patterns failed to improve reaching. Data indicate that the Mthal may be an effective site to treat akinesia, but the pattern of stimulation is critical for improving reaching in parkinsonian rats.