We investigated the origins of oscillations under essential tremor (ET) by building a computational model of the cortico-cerebello-thalamo-cortical loop. It showed that an alteration of amplitudes and decay times of the GABAergic currents to the dentate nucleus can facilitate sustained oscillatory activity at tremor frequency throughout the network as well as a robust bursting activity in the thalamus, which is consistent with observations of thalamic tremor cells in ET patients. Tremor-related oscillations initiated in small neural populations and spread to a larger network as the synaptic dysfunction increased, while thalamic high-frequency stimulation suppressed tremor-related activity in thalamus but increased the oscillation frequency in the olivocerebellar loop.
Model Type: Realistic Network
Region(s) or Organism(s): Cerebellum; Thalamus; Brainstem
Cell Type(s): Cerebellum Purkinje GABA cell; Cerebellum deep nucleus neuron; Inferior olive neuron
Transmitters: Gaba
Model Concept(s): Oscillations
Simulation Environment: NEURON
References:
Zhang X, Santaniello S. (2019). Role of cerebellar GABAergic dysfunctions in the origins of essential tremor Proceedings of the National Academy of Sciences.