Woodward Kathryn, Apps Richard, Goodfellow Marc, Cerminara Nadia L
School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.
Department of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, United Kingdom.
Front Syst Neurosci. 2022 Jul 28;16:899446. doi: 10.3389/fnsys.2022.899446. eCollection 2022.
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.
特发性震颤（ET）是一种常见的运动障碍，其特征为上肢与姿势或运动相关的震颤。小脑回路内的异常被认为是ET发病机制的基础，导致丘脑 - 皮质网络内出现异常的同步振荡活动，进而引发震颤。骆驼蓬碱可在小脑中产生病理性振荡，并引发一种在表型上类似于ET的震颤。然而，骆驼蓬碱诱发震颤时小脑 - 丘脑 - 皮质回路中的神经网络动力学仍不清楚，包括行为状态可能影响回路相互作用的方式。在此，我们研究了骆驼蓬碱在休息和运动期间对小脑 - 丘脑 - 皮质振荡的影响。在清醒行为的大鼠中，同时记录感觉运动皮层的脑电图（EEG）以及丘脑和内侧小脑核的局部场电位（LFP），并使用肌电图（EMG）和加速度计测量震颤。分析比较了全身注射骆驼蓬碱（10mg/kg，腹腔注射）前后的神经振荡，以及大鼠休息与运动期间的相干性。在运动期间，骆驼蓬碱增加了9 - 15Hz行为性震颤的幅度，并增加了丘脑LFP与震颤的相干性。然而，内侧小脑核和小脑蚓部LFP与震颤的相干性在休息时保持不变。这些发现表明，骆驼蓬碱诱发的小脑振荡独立于行为状态以及震颤幅度的相关变化。相比之下，丘脑振荡依赖于行为状态和震颤幅度的相关变化。本研究为小脑 - 丘脑 - 皮质网络相互作用在震颤中的作用提供了新的见解，即在骆驼蓬碱模型中，丘脑皮质而非小脑回路中的神经振荡可受运动和/或行为性震颤幅度影响。
