Bifurcations for counterintuitive post-inhibitory rebound spike related to absence epilepsy and Parkinson disease.

Seizures are caused by increased neuronal firing activity resulting from reduced inhibitory effect and enhancement of inhibitory modulation to suppress this activity is used as a therapeutic tool. However, recent experiments have shown a counterintuitive phenomenon that inhibitory modulation does not suppress but elicit post-inhibitory rebound (PIR) spike along with seizure to challenge the therapeutic tool. The nonlinear mechanism to avoid the PIR spike can present theoretical guidance to seizure treatment. This paper focuses on identifying credible bifurcations that underlie PIR spike by modulating multiple parameters in multiple theoretical models. The study identifies a codimension-2 bifurcation called saddle--node homoclinic orbit (SNHO_B), which is an intersection between saddle node bifurcation on invariant cycle (SNIC) and other two bifurcations. PIR spike cannot be evoked for the SNIC far from the SNHO_B but induced for the SNIC close to the SNHO_B, which extends the bifurcation condition for PIR spike from the well-known Hopf to SNIC. Especially, in a thalamic neuron model, increases of conductance of T-type Ca²⁺ (T _Ca) channel induce SNIC bifurcation approaching to the SNHO_B to elicit PIR spikes, closely matching experimental results of the absence seizure or Parkinson diseases. Such results imply that, when inhibition is employed to relieve absence seizure and Parkinson diseases related to PIR spike, modulating SNIC to get far from the SNHO_B to avoid PIR spike is the principle. The study also addresses the complex roles of T _Ca current and comprehensive relationships between PIR spike and nonlinear conceptions such as bifurcation types and shapes of threshold curve. [ABSTRACT FROM AUTHOR]