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

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.