Enhanced Long-Term Potentiation-Like Plasticity of the Trigeminal Blink Reflex Circuit in Blepharospasm

Abstract

Benign essential blepharospasm (BEB) is a focal cranial dystonia affecting eye closure. Here, we tested the hypothesis that BEB is associated with abnormal plasticity of the neuronal circuits mediating reflex blinks. In patients with BEB and healthy age-matched controls, we used the conditioning protocol introduced by Mao and Evinger (2001) to induce long-term potentiation (LTP)-like plasticity in trigeminal wide dynamic range neurons of the blink reflex circuit. High-frequency trains of electrical stimuli were repeatedly given over the right supraorbital nerve (SO) and timed to coincide with the R2 response elicited by a preceding SO stimulus. High-frequency stimulation (HFS) resulted in a long-lasting and input-specific potentiation of the R2 response in both groups, yet the facilitation of the R2 response was markedly increased in patients relative to controls. Botulinum toxin (BTX) injections in both orbicularis oculi muscles normalized the previously enhanced LTP-like plasticity of the R2 response. The increased responsiveness to HFS provides first-time evidence that LTP-like plasticity is increased in the trigeminal reflex circuit of patients affected by BEB. The results also show that the enhanced modifiability is not fixed in BEB, because BTX injections can transiently restore normal LTP-like plasticity. We propose that an abnormal corneal input induced by excessive blinking exacerbates increased LTP-like plasticity in BEB. BTX treatment removes the latter and restores plasticity toward normal values. Our results support the concept that maladaptive reorganization contributes to the pathophysiology of focal dystonias.

Blepharospasm and the modulation of cortical excitability in primary and secondary motor areas

“…It may, however, secondarily induce a plastic change in the corticobasal-thalamofrontal motor loop, as central plastic adaptations in BEB patients after treatment with botulinum toxin have been documented. 21 Dysfunction of the basal ganglia (BG), and consequently on the output structure of BG (globus pallidus internus [GPi]/substantia nigra pars reticulata [SNr]), may also lead to a decrease or loss of the inhibitory control exerted by the BG on the blink reflex circuitry. This would increase the excitability of this circuit.…”

Experiential Modification of the Trigeminal Reflex Blink Circuit

“…First, the sensory pathways of the trigeminal system exhibit significant modifiability throughout life (Nicolelis et al, 1998;Guido et al, 2001). Second, the presentation of high-frequency trigeminal stimuli to adult humans produces long-term potentiation-and long-term depression (LTD)-like effects in trigeminal reflex blinks (Mao and Evinger, 2001;Battaglia et al, 2006;Quartarone et al, 2006), and low-frequency stimulation also produces LTD-like modification of reflex blinks (Schorr and Ellrich, 2002). These data suggest that synaptic plasticity occurs in trigeminal blink circuits and may occur as early as the first trigeminal synapse.…”

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

“…PD also disrupts reflex plasticity (Battaglia et al 2006;Chong et al 2000;Horak et al 1992;MacAskill et al 2002;White et al 1983). The trigeminal blink reflex provides a model for this type of plasticity.…”