"Deep brain stimulation (DBS) is a successful clinical therapy for a wide range of neurological disorders; however, the physiological mechanisms of DBS remain unresolved. While many different hypotheses currently exist, our analyses suggest that high frequency (~100?Hz) stimulation-induced synaptic suppression represents the most basic concept that can be directly reconciled with experimental recordings of spiking activity in neurons that are being driven by DBS inputs. Objective The goal of this project was to develop a simple model system to characterize the excitatory post-synaptic currents (EPSCs) and action potential signaling generated in a neuron that is strongly connected to pre-synaptic glutamatergic inputs that are being directly activated by DBS. Methods We used the Tsodyks-Markram (TM) phenomenological synapse model to represent depressing, facilitating, and pseudo-linear synapses driven by DBS over a wide range of stimulation frequencies. The EPSCs were then used as inputs to a leaky integrate-and-fire neuron model and we measured the DBS-triggered post-synaptic spiking activity. Results Synaptic suppression was a robust feature of high frequency stimulation, independent of the synapse type. As such, the TM equations were used to define alternative DBS pulsing strategies that maximized synaptic suppression with the minimum number of stimuli. ..."
Region(s) or Organism(s): Neocortex
Cell Type(s): Abstract integrate-and-fire leaky neuron
Simulation Environment: MATLAB
Implementer(s): Farokhniaee, AmirAli [aafarokh at gmail.com]