Design and Analysis of Staged Mutual Inhibition to Implement Bi-Stable Neuronal Toggle Switch

Analogous to the fundamental role of flip-flops in electronics, bi-stable biological neuronal toggle switches appear frequently in neuronal circuitry in vivo. Mutual inhibition, which is considered to be the primary mechanism behind bi-stability, has been the subject of substantial theoretical and experimental studies. However, evaluation of its precise timing requirement using advanced computational models has been missing. In this work, we suggest that direct mutual inhibition fails as an effective toggle switch and propose an alternative circuit design, termed staged mutual inhibition, to improve robustness. Using Leaky Integrate-and- Fire model, we perform sensitivity analysis and simulations based on relevant biophysical parameters to quantitatively demonstrate the advantages of staged vs. direct mutual inhibition. We believe that our approach to neuronal circuitry can benefit neuro-inspired designs.