A role for NMDAR-dependent cerebellar plasticity in adaptive control of saccades in humans.

S Colnaghi, P Colagiorgio, M Versino, G Koch, E D'Angelo, S Ramat

Journal: Brain stimulation 2018;10(4):817-827

PMID: 28501325

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Saccade pulse amplitude adaptation is mediated by the dorsal cerebellar vermis and fastigial nucleus. Long-term depression at the parallel fibre-Purkinjie cell synapses has been suggested to provide a cellular mechanism for the corresponding learning process. The mechanisms and sites of this plasticity, however, are still debated.

OBJECTIVE

To test the role of cerebellar plasticity phenomena on adaptive saccade control.

METHODS

We evaluated the effect of continuous theta burst stimulation (cTBS) over the posterior vermis on saccade amplitude adaptation and spontaneous recovery of the initial response. To further identify the substrate of synaptic plasticity responsible for the observed adaptation impairment, subjects were pre-treated with memantine, an N-methyl-d-aspartate receptor (NMDAR) antagonist.

RESULTS

Amplitude adaptation was altered by cTBS, suggesting that cTBS interferes with cerebellar plasticity involved in saccade adaptation. Amplitude adaptation and spontaneous recovery were not affected by cTBS when recordings were preceded by memantine administration.

CONCLUSION

The effects of cTBS are NMDAR-dependent and are likely to involve long-term potentiation or long-term depression at specific synaptic connections of the granular and molecular layer, which could effectively take part in cerebellar motor learning.

Address: Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Via Forlanini 2, 27100 Pavia, Italy; Laboratory of Neuro-otology and Neuro-ophtalmology, C. Mondino National Neurological Institute, via Mondino 2, 27100 Pavia, Italy. Electronic address: [email protected].; Department of Electrical, Computer and Biomedical Engineering, University of Pavia, via Ferrata 5, 27100 Pavia, Italy.; Laboratory of Neuro-otology and Neuro-ophtalmology, C. Mondino National Neurological Institute, via Mondino 2, 27100 Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, via Forlanini 6, 27100 Pavia, Italy.; Laboratorio di Neurologia Clinica e Comportamentale, Fondazione S. Lucia IRCCS, via Ardeatina 306, 00179 Rome, Italy; Dipartimento di Neurologia, Policlinico Tor Vergata, viale Oxford 81, 00133 Rome, Italy.; Department of Brain and Behavioral Sciences, University of Pavia, via Forlanini 6, 27100 Pavia, Italy; Brain Connectivity Center, C. Mondino National Neurological Institute, via Mondino 2, 27100 Pavia, Italy.

DOI: 10.1016/j.brs.2017.05.001

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MeSH Terms: Adaptation, Physiological, Adult, Cerebellar Nuclei, Excitatory Amino Acid Antagonists, Female, Humans, Long-Term Potentiation, Male, Memantine, Receptors, N-Methyl-D-Aspartate, Saccades