An Account of Models of Molecular Circuits for Associative Learning with Reinforcement Effect and Forced Dissociation

The development of synthetic biology has enabled us to make massive progress on biotechnology and to approach research questions from a brand new perspective. In particular, the design and study of gene regulatory networks in vitro, in vivo and in silico, have played an increasingly indispensable role in understanding and controlling biological phenomena. Among them, it is of great interest to understand how associative learning is formed at the molecular circuit level. Noticeably, mathematical models have been increasingly used to predict the behaviors of molecular circuits. The Fernando’s model, which is thought to be one of the first works in this line of research using the Hill equation, attempted to design a synthetic circuit that mimics Hebbian learning in the neural network architecture. In this article, we carry out in-depth computational analysis of the model and demonstrate that the reinforcement effect can be achieved by choosing the proper parameter values. We also construct a novel circuit that can demonstrate forced dissociation, which was not observed in the Fernando’s model. Our work can be readily used as reference for synthetic biologists who consider implementing the circuits of this kind in biological systems.