Cerebello-Thalamo-Cortical Network Dynamics in the Harmaline Rodent Model of Essential Tremor

Kathryn Woodward, Richard Apps, Marc Goodfellow, Nadia L Cerminara*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
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Abstract

Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-related tremor of the upper limbs. Abnormalities within cerebellar circuits are thought to underlie the pathogenesis of ET, resulting in aberrant synchronous oscillatory activity within the thalamo-cortical network leading to tremors. Harmaline produces pathological oscillations within the cerebellum, and a tremor that phenotypically resembles ET. However, the neural network dynamics in cerebellar-thalamo-cortical circuits in harmaline-induced tremor remains unclear, including the way circuit interactions may be influenced by behavioural state. Here, we examined the effect of harmaline on cerebello-thalamo-cortical oscillations during rest and movement. EEG recordings from the sensorimotor cortex and local field potentials (LFP) from thalamic and medial cerebellar nuclei were simultaneously recorded in awake behaving rats, alongside measures of tremor using EMG and accelerometery. Analyses compared neural oscillations before and after systemic administration of harmaline (10 mg/kg, I.P), and coherence across periods when rats were resting vs. moving. During movement, harmaline increased the 9-15 Hz behavioural tremor amplitude and increased thalamic LFP coherence with tremor. Medial cerebellar nuclei and cerebellar vermis LFP coherence with tremor however remained unchanged from rest. These findings suggest harmaline-induced cerebellar oscillations are independent of behavioural state and associated changes in tremor amplitude. By contrast, thalamic oscillations are dependent on behavioural state and related changes in tremor amplitude. This study provides new insights into the role of cerebello-thalamo-cortical network interactions in tremor, whereby neural oscillations in thalamocortical, but not cerebellar circuits can be influenced by movement and/or behavioural tremor amplitude in the harmaline model.

Original languageEnglish
Article number899446
JournalFrontiers in Systems Neuroscience
Volume16
DOIs
Publication statusPublished - 28 Jul 2022

Bibliographical note

Funding Information:
This work was supported by the Medical Research Council UK (G1100626) and the BBSRC (BB/P000959/1) to NC and RA. This work was supported in part by grant MR/N0137941/1 for the GW4 BIOMED MRC DTP, awarded to the Universities of Bath, Bristol, Cardiff and Exeter from the Medical Research Council (MRC)/UKRI.

Publisher Copyright:
Copyright © 2022 Woodward, Apps, Goodfellow and Cerminara.

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