" ... High frequency (~130 Hz) deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease (PD). Direct modulation of the hyperdirect pathway, defined as cortical layer V pyramidal neurons that send an axon collateral to the subthalamic nucleus (STN), has emerged as a possible component of the therapeutic mechanisms. ...We found robust AP propagation throughout the complex axonal arbor of the hyperdirect neuron. Even at therapeutic DBS frequencies, stimulation induced APs could reach all of the intracortical axon terminals with ~100% fidelity. The functional result of this high frequency axonal driving of the thousands of synaptic connections made by each directly stimulated hyperdirect neuron is a profound synaptic suppression that would effectively disconnect the neuron from the cortical circuitry. ..."
Cell Type(s): Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell
Simulation Environment: NEURON
Anderson RW, Farokhniaee A, Gunalan K, Howell B, McIntyre CC. (2018). Action potential initiation, propagation, and cortical invasion in the hyperdirect pathway during subthalamic deep brain stimulation Brain Stimulation.