Regulating epileptiform discharges by heterogeneous interneurons in thalamocortical model

Abstract

Inhibitory interneurons in the cortex are abundant and have diverse roles, classified as parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal polypeptide (VIP) according to chemically defined categories. Currently, their involvement with seizures has been partially uncovered in physiological terms. Here, we propose a corticothalamic model containing heterogeneous interneurons to study the effects of various interneurons on absence seizure dynamics by means of optogenetic stimulation. First, the important role of feedforward inhibition caused by SRN→PV→PN projections on seizures is verified. Then, we demonstrate that light activation targeting either PV or SOM INs can control seizures. Finally, with different inhibition contributions from PV INs and SOM INs, the possible disinhibitory effect of blue light acting on VIP INs is mainly discussed. The results suggest that depending on the inhibition degree of both types, the disinhibition brought about by the VIP INs will trigger seizures, will control seizures, and will not work or cause the PNs to tend toward a high saturation state with high excitability. The circuit mechanism and the related bifurcation characteristics in various cases are emphatically revealed. In the model presented, in addition to Hopf and saddle-node bifurcations, the system may also undergo period-doubling and torus bifurcations under stimulus action, with more complex dynamics. Our work may provide a theoretical basis for understanding and further exploring the role of heterogeneous interneurons, in particular, the VIP INs, a novel target, in absence seizures.