Neural correlates of tremor epochs in a rat model of essential tremor



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tarix26.03.2018
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Neural correlates of tremor epochs in a rat model of essential tremor
Gilad Jacobson1,2, Iddo Lev4, Dana Porrat3, Dana Cohen4 and Yosef Yarom1,2
1Department of Neurobiology, Life Science Institute and 2The Interdisciplinary Center for Neural Computation, Edmond Safra Campus, Jerusalem 91904, Israel.

3The Benin School of Engineering and Computer Science, The Hebrew University of Jerusalem, Edmond Safra Campus, Jerusalem 91904, Israel.

4The Gonda Multidisiplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.
Essential tremor is the most common movement disorder and is one of the most prevalent neurological disorders, affecting 0.5-5% of the population. Essential tremor is characterised by episodic muscle tremor at around 10 Hz, amplified during movement. One of the classical animal models for essential tremor is harmaline-induced tremor, exhibiting similar characteristics to the pathology and similar drug relief, and known to involve the inferior olive. The olivary hypothesis proposes that harmaline induced tremor results from a direct effect of harmaline on the T-type calcium current in olivary neurons, increasing their tendency to oscillate. However, it is yet unclear if and how this neuronal mechanism underlies the episodic nature of essential tremor.

To resolve this question, we recorded neuronal activity in the cerebellar cortex of freely moving rats using chronically-implanted micro-electrode arrays before and after harmaline injection (15mg/kg, i.p). After harmaline application, 10-15 Hz rhythmicity appeared in the multi-unit activity, probably reflecting the olivary input through the climbing fibres. The rats exhibited strong, episodic tremor in the same frequency range, as recorded by EMG electrodes implanted in the limbs. We tested two possible explanations for the episodic nature of tremor: 1) that tremor results from recruitment of olivary units; or 2) that tremor results from the phase-locking of continuously oscillating olivary units. To study the relationships of the amplitude and phase in the different channels, we extracted the amplitude envelopes of the multi-unit channels, and studied the frequency band elevated after harmaline application (usually in the 7.5-15 Hz range). Using signal-analysis methods, we studied the amplitude and phase relationships across all simultaneously recorded channels, and found episodic common amplitude excursions and phase-locking epochs, lasting several seconds. Phase-locking epochs appeared to be more robust and prolonged. We propose that these phase-locking epochs may underlie the epochs of elevated tremor.
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