Switching in Cerebellar Stellate Cell Excitability in Response to a Pair of Inhibitory/Excitatory Presynaptic Inputs:...

Cerebellar stellate cells form inhibitory synapses with Purkinje cells, the sole output of the cerebellum. Upon stimulation by a pair of varying inhibitory and fixed excitatory presynaptic inputs, these cells do not respond to excitation (i.e., do not generate an action potential) when the magnitude of the inhibition is within a given range, but they do respond outside this range. We previously used a revised Hodgkin-Huxley type of model to study the nonmonotonic first-spike latency of these cells and their temporal increase in excitability in whole cell configuration (termed run-up). Here, we recompute these latency profiles using the same model by adapting an efficient computational technique, the two-point boundary value problem, that is combined with the continuation method. We then extend the study to investigate how switching in responsiveness, upon stimulation with presynaptic inputs, manifests itself in the context of run-up. A three-dimensional reduced model is initially derived from the original six-dimensional model and then analyzed to demonstrate that both models exhibit type 1 excitability possessing a saddle-node on an invariant cycle (SNIC) bifurcation when varying the amplitude of $$. Using slow-fast analysis, we show that the original model possesses three equilibria lying at the intersection of the critical manifold of the fast subsystem and the nullcline of the slow variable $$ (the inactivation of the A-type K$$ channel), the middle equilibrium is of saddle type with two-dimensional stable manifold (computed from the reduced model) acting as a boundary between the responsive and non-responsive regimes, and the (ghost of) SNIC is formed when the $$-nullcline is (nearly) tangential to the critical manifold. We also show that the slow dynamics associated with (the ghost of) the SNIC and the lower stable branch of the critical manifold are responsible for generating the nonmonotonic first-spike latency. These results thus provide important insight into the complex dynamics of stellate cells.