High frequency stimulation of the Subthalamic Nucleus (Rubin and Terman 2004)


" ... Using a computational model, this paper considers the hypothesis that DBS works by replacing pathologically rhythmic basal ganglia output with tonic, high frequency firing. In our simulations of parkinsonian conditions, rhythmic inhibition from GPi to the thalamus compromises the ability of thalamocortical relay (TC) cells to respond to depolarizing inputs, such as sensorimotor signals. High frequency stimulation of STN regularizes GPi firing, and this restores TC responsiveness, despite the increased frequency and amplitude of GPi inhibition to thalamus that result. We provide a mathematical phase plane analysis of the mechanisms that determine TC relay capabilities in normal, parkinsonian, and DBS states in a reduced model. This analysis highlights the differences in deinactivation of the low-threshold calcium T -current that we observe in TC cells in these different conditions. ..."

Model Type: Realistic Network; Neuron or other electrically excitable cell

Region(s) or Organism(s): Thalamus; Basal ganglia; Subthalamic Nucleus

Cell Type(s): Thalamus geniculate nucleus/lateral principal GLU cell; Subthalamus nucleus projection neuron; Globus pallidus neuron

Currents: I Na,t; I T low threshold; I K; I Calcium

Model Concept(s): Activity Patterns; Parkinson's; Deep brain stimulation

Simulation Environment: XPPAUT

References:

Rubin JE, Terman D. (2004). High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model. Journal of computational neuroscience. 16 [PubMed]


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