Patterned, But Not Tonic, Optogenetic Stimulation in Motor Thalamus Improves Reaching in Acute Drug-Induced Parkinsonian Rats

S. Seeger-Armbruster, C. Bosch-Bouju, S. T. C. Little, R. A. Smither, S. M. Hughes, B. I. Hyland, L. C. Parr-Brownlie
Journal of Neuroscience. 2015-01-21; 35(3): 1211-1216
DOI: 10.1523/jneurosci.3277-14.2015

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1. J Neurosci. 2015 Jan 21;35(3):1211-6. doi: 10.1523/JNEUROSCI.3277-14.2015.

Patterned, but not tonic, optogenetic stimulation in motor thalamus improves
reaching in acute drug-induced Parkinsonian rats.

Seeger-Armbruster S(1), Bosch-Bouju C(2), Little ST(2), Smither RA(1), Hughes
SM(3), Hyland BI(1), Parr-Brownlie LC(4).

Author information:
(1)Departments of Physiology.
(2)Anatomy, and.
(3)Biochemistry, Otago School of Medical Science, Brain Health Research Centre,
University of Otago, Dunedin 9054, New Zealand.
(4)Anatomy, and .

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

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