Controlling the onset of Hopf bifurcation in the Hodgkin-Huxley model

It is a challenging problem to establish safe and simple therapeutic methods for various complicated diseases of the nervous system, particularly dynamical diseases such as epilepsy, Alzheimer's disease, and Parkinson's disease. From the viewpoint of nonlinear dynamical systems, a dynamical disease can be considered to be caused by a bifurcation induced by a change in the values of one or more regulating parameter. Therefore, the theory of bifurcation control may have potential applications in the diagnosis and therapy of dynamical diseases. In this study, we employ a washout filter-aided dynamic feedback controller to control the onset of Hopf bifurcation in the Hodgkin-Huxley (HH) model. Specifically, by the control scheme, we can move the Hopf bifurcation to a desired point irrespective of whether the corresponding steady state is stable or unstable. In other words, we are able to advance or delay the Hopf bifurcation, so as to prevent it from occurring in a certain range of the externally applied current. Moreover, we can control the criticality of the bifurcation and regulate the oscillation amplitude of the bifurcated limit cycle. In the controller, there are only two terms: the linear term and the nonlinear cubic term. We show that while the former determines the location of the Hopf bifurcation, the latter regulates the criticality of the Hopf bifurcation. According to the conditions of the occurrence of Hopf bifurcation and the bifurcation stability coefficient, we can analytically deduce the linear term and the nonlinear cubic term, respectively. In addition, we also show that mixed-mode oscillations (MMOs), featuring slow action potential generation, which are frequently observed in both experiments and models of chemical and biological systems, appear in the controlled HH model. It is well known that slow firing rates in single neuron models could be achieved only by type-I neurons. However, the controlled HH model is still classified as a type-II neuron, as is the original HH model. We explain that the occurrence of MMOs can be related to the presence of the canard explosion where a small oscillation grows through a sequence of canard cycles to a relaxation oscillation as the control parameter moves through an interval of exponentially small width.