Deep brain stimulation-induced two manners to eliminate bursting for Parkinson's diseases: synaptic current and bifurcation mechanisms.

Although deep brain stimulation (DBS) is effective in treating Parkinson's disease (PD) related to bursting, the underlying mechanisms remain unclear. In the present paper, the dynamical and synaptic mechanisms are studied in a basal ganglia-thalamus model. Firstly, slow and large oscillations of synaptic gating variables/currents are identified as the cause of the irregular and non-synchronous bursting for PD, indicating that interruption of these slow modulations may be a feasible measure to treat PD. Secondly, strong DBS with high frequency applied to subthalamic nucleus (STN) can induce fast synchronous spiking in both STN and external globus pallidus (GPe), then interrupt the slow gating variables, thereby eliminating the irregular bursting. Meanwhile, the gating variables of the excitatory and inhibitory synapses respectively from STN and GPe to the internal globus pallidus (GPi) become fast. Finally, competition between these two opposite synapses can induce two manners to eliminate the bursting of GPi and restore the normal state, appearing in vast majority of parameter space composed of multiple synaptic conductances. One is the synchronous silence of GPi, and the other the synchronous regular fast spiking, which occurs for large conductance of the inhibitory and excitatory synapse, respectively. Both result in regular spiking of thalamus, via interrupting slow gating variables of synapse projected to thalamus. In addition, as the two conductances approach each other, the synaptic current to GPi oscillates around zero slowly, resulting in irregular firings of GPi and thalamus for PD in a narrow parameter space. Furthermore, the bursting observed in PD before DBS and three types of electrical activities of GPi during DBS are explained, using a saddle-node bifurcation of limit cycles and oscillation patterns of synaptic current. The distinction from the post inhibitory rebound bursting reported in previous studies is discussed. The results present the mechanisms for DBS to treat PD via eliminating bursting in wide parameter region.