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The Journal of Neuroscience, January 11, 2006, 26(2):716-721; doi:10.1523/JNEUROSCI.3948-05.2006

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

Angelo Quartarone,¹ Antonino Sant'Angelo,¹ Fortunato Battaglia,² Sergio Bagnato,^1,3 Vincenzo Rizzo,¹ Francesca Morgante,¹ John C. Rothwell,⁴ Hartwig R. Siebner,⁵ and Paolo Girlanda¹

¹Departments of Neurosciences, Psychiatric and Anaesthesiological Sciences, University of Messina, 98125 Messina, Italy, ²Department of Physiology and Pharmacology, City College University of New York Medical School, New York, New York 10012, ³Fondazione Istituto San Raffaele-G. Giglio, 90015 Cefalù (Pa), Italy, ⁴Sobell Department of Neurophysiology, Institute of Neurology, Queen Square, London WC1N BG3, United Kingdom, and ⁵Department of Neurology, Christian-Albrechts-University, D-24105 Kiel, Germany

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.

Key words: blepharospasm; blink reflex; focal dystonia; long-term potentiation; LTP; maladaptive plasticity; basal ganglia

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Received April 29, 2005; revised September 19, 2005; accepted October 16, 2005.

This article has been cited by other articles:

				A Quartarone, F Morgante, A Sant'Angelo, V Rizzo, S Bagnato, C Terranova, H R Siebner, A Berardelli, and P Girlanda Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia J. Neurol. Neurosurg. Psychiatry, September 1, 2008; 79(9): 985 - 990. [Abstract] [Full Text] [PDF]

				M Fiorio, M Tinazzi, A Scontrini, C Stanzani, M Gambarin, A Fiaschi, G Moretto, G Fabbrini, and A Berardelli Tactile temporal discrimination in patients with blepharospasm J. Neurol. Neurosurg. Psychiatry, July 1, 2008; 79(7): 796 - 798. [Abstract] [Full Text] [PDF]

				C. Dauvergne and C. Evinger Experiential Modification of the Trigeminal Reflex Blink Circuit J. Neurosci., September 26, 2007; 27(39): 10414 - 10422. [Abstract] [Full Text] [PDF]

				D. Martino, G. Defazio, G. Abbruzzese, P. Girlanda, M. Tinazzi, G. Fabbrini, M. S. Aniello, L. Avanzino, C. Colosimo, G. Majorana, et al. Head trauma in primary cranial dystonias: a multicentre case-control study J. Neurol. Neurosurg. Psychiatry, March 1, 2007; 78(3): 260 - 263. [Abstract] [Full Text] [PDF]

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