Thalamo-cortical network is associated with harmaline-induced tremor in rodent model

Essential tremor (ET) is the most frequent form of pathologic tremor and one of the most common adult-onset neurologic impairments. However, underlying mechanisms by which structural alterations within the tremor circuit generate the pathological state and how rhythmic neuronal activities propagate and drive tremor remains unclear. Harmaline (HA)-induced tremor model has been most frequently utilized animal model for ET studies, however, there is still a dearth of knowledge over the degree to whether HA-induced tremor mimics the actual underlying pathophysiology of ET, particularly the involvement of thalamo-cortical region. In this study, we investigated the electrophysiological response of the motor circuit including the ventrolateral thalamus (vlTh) and the primary motor cortex (M1), and the modulatory effect of thalamic deep brain stimulation (DBS) using a rat HA-induced tremor model. We found that the theta and high-frequency oscillation (HFO) band power significantly increased after HA administration in both vlTh and M1, and the activity was modulated by the tremor suppression drug (propranolol) and the thalamic DBS. The theta band phase synchronization between the vlTh and M1 was significantly enhanced during the HA-induced tremor, and the transition of cross-frequency coupling in vlTh was found to be associated with the state of HA-induced tremor. Our findings support that the HA tremor could be useful as a valid preclinical model of ET in the context of thalamo-cortical neural network interaction.