Trigeminal high-frequency stimulation produces short- and long-term modification of reflex blink gain

Abstract

Reflex blinks provide a model system for investigating motor learning in normal and pathological states. We investigated whether high-frequency stimulation (HFS) of the supraorbital branch of the trigeminal nerve before the R2 blink component (HFS-B) decreases reflex blink gain in alert rats. As with humans (Mao JB, Evinger C. J Neurosci 21: RC151, 2001), HFS-B significantly reduced blink size in the first hour after treatment for rats. Repeated days of HFS-B treatment produced long-term depression of blink circuits. Blink gain decreased exponentially across days, indicating a long-term depression of blink circuits. Additionally, the HFS-B protocol became more effective at depressing blink amplitude across days of treatment. This depression was not habituation, because neither long- nor short-term blink changes occurred when HFS was presented after the R2. To investigate whether gain modifications produced by HFS-B involved cerebellar networks, we trained rats in a delay eyelid conditioning paradigm using HFS-B as the unconditioned stimulus and a tone as the conditioned stimulus. As HFS-B depresses blink circuits and delay conditioning enhances blink circuit activity, occlusion should occur if they share neural networks. Rats acquiring robust eyelid conditioning did not exhibit decreases in blink gain, whereas rats developing low levels of eyelid conditioning exhibited weak, short-term reductions in blink gain. These results suggested that delay eyelid conditioning and long-term HFS-B utilize some of the same cerebellar circuits. The ability of repeated HFS-B treatment to depress trigeminal blink circuit activity long term implied that it may be a useful protocol to reduce hyperexcitable blink circuits that underlie diseases like benign essential blepharospasm.

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

“…The therapeutic effectiveness of high-frequency STN DBS may be a result of reducing this 10-to 30-Hz beta-oscillation. Consistent with this interpretation, beta frequency STN DBS of normal rats causes the same reflex blink abnormalities as occur in PD patients (Kaminer et al 2014). If 130-Hz STN DBS reduces beta band oscillations in 6-OHDA lesioned rats, then we predict that this frequency will eliminate blink abnormalities in 6-OHDA lesioned rats, whereas STN DBS in the beta frequency range will not improve blinking.…”

“…The threshold current was determined at the beginning of each day for each rat. Threshold varied little across days (Ryan et al 2014). We attempted to maximize the effect of STN DBS on blinking without causing any abnormal motor behavior.…”

“…To investigate the effects of 130-or 16-Hz STN DBS on blink reflex plasticity, we utilized a protocol previously designed to depress blink reflex gain (Mao and Evinger 2001), adapted for use in rodents (Ryan et al 2014). A 2T SO high-frequency stimulus (HFS, 400 Hz) was delivered before the R2 component of the SO-evoked blink reflex (HFS-B).…”

“…We, however, investigated the effects of HFS-B on the R1 component of the blink reflex, as it is the largest component of the blink reflex in nonprimate mammals and exhibits the same changes as R2 in the HFS-B paradigm (Ryan et al 2014). We normalized all within-day blink amplitudes by dividing each OOemg amplitude by the median pre-HFS OOemg amplitude.…”

“…The trigeminal blink reflex provides a model for this type of plasticity. Depending upon its timing relative to reflex blink occurrence, high-frequency stimulation of the supraorbital branch of the trigeminal nerve can increase or decrease the amplitude of subsequent reflex blinks for a period of at least 1 h (Mao and Evinger 2001;Ryan et al 2014). Both PD in humans and 6-OHDA lesions in rats impair this form of trigeminal blink reflex plasticity (Battaglia et al 2006;Kaminer et al 2014).…”