Channelopathy and anticipated synchronization: effect of the W1204R (Na_v1.1) epileptogenic mutation in an SRI microcircuit

Anticipated synchronization (AS) is a regime where a receiver neuron fires before the sender that excites it, preserving causality. Although a sender-receiver-interneuron (SRI) neuronal motif transitions from delayed synchronization (DS) to AS upon increasing inhibitory conductance, it remains to be elucidated whether this depends on the neuronal excitability class. Here, three models are contrasted within the SRI circuit: Hodgkin-Huxley (HH) and two GEFS+ variants based on Na_v1.1 channel kinetics (control and the W1204R epileptogenic mutation). Excitability analysis reveals that HH is Class 2 (subcritical Hopf bifurcation), whereas the GEFS+ variants are Class 1. The W1204R mutation shifts the transfer (f-I) curve without altering its excitability class. For a rigorous parametric comparison, the models were evaluated at equivalent operating points by matching the receiver's intrinsic frequency. Under these conditions, the parameter space was analyzed to determine the DS-AS transition thresholds according to the excitation-inhibition balance. Using phase response curves (PRC), the plane defined by the operating point and the synaptic conductance ratio was characterized. These findings demonstrate how the dynamic divergences of the models modulate synchronization regimes, highlighting the role of intrinsic excitability in the propagation of epileptogenic activity.