Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats

Abstract

Kaminer J, Thakur P, Evinger C. Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA-lesioned rats. J Neurophysiol 113: 3038 -3046, 2015. First published February 11, 2015 doi:10.1152/jn.01072.2014.-Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short-and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms.

Translational neurophysiology of Parkinson's disease: can't blink on an eye blink

“…However, the change in the steady-state neural response gain might not affect dynamic motor function such as rate or rhythmicity of the spontaneous blinks. This concept is compatible with the recent report by Kaminer et al (2015).…”

“…It is therefore possible that firing patterns of substantia nigra pars reticulata determine the spontaneous blink rate and rhythmicity, just like eye movements. This prediction is also supported by the recent findings that subthalamic deep brain stimulation did not restore abnormal spontaneous blink rate and rhythm (Kaminer et al 2015).…”

“…The suppression of beta-band oscillations with high-frequency stimulation might treat the blink abnormalities. Indeed, high-frequency stimulation of the subthalamus resolved blink hyperreflexia and restored blink reflex plasticity, but it did not affect the abnormal rate and rhythm of the spontaneous blinks (Kaminer et al 2015).…”

“…These endeavors are not only useful to characterize phenomenology of degenerative disorders of basal ganglia, but they also have paramount importance in objectively characterizing the course of the disease and understanding the physiological basis of its treatment. Three types of eyelid movement abnormalities are notable in the experimental models of Parkinson's disease: blink hyperreflexia, impaired blink reflex plasticity, and reduced rate and impaired rhythm of the spontaneous blinks (Basso et al 1993;Kaminer et al 2011Kaminer et al , 2014Kaminer et al , 2015.…”

“…In a recent elegant study of the rodent model with Parkinson's disease, Kaminer et al (2015) stimulated the subthalamus with beta-band (15-20 Hz) and high-frequency (130 Hz) electrical pulses. The idea was that if the hypersynchrony in beta band is the cause for eyelid abnormality in Parkinson's disease, then the low-frequency stimulation in the beta band might cause or worsen the eyelid abnormalities.…”