Bifurcation analysis of a delay differential equation model associated with the induction of long-term memory

The ability to form long-term memories is an important function for the nervous system, and the formation process is dynamically regulated through various transcription factors, including CREB proteins. In this paper, we investigate the dynamics of a delay differential equation model for CREB protein activities, which involves two positive and two negative feedbacks in the regulatory network. We discuss the dynamical mechanisms underlying the induction of long-term memory, in which bistability is essential for the formation of long-term memory, while long time delay can destabilize the high level steady state to inhibit the long-term memory formation. The model displays rich dynamical response to stimuli, including monostability, bistability, and oscillations, and can transit between different states by varying the negative feedback strength. Introduction of a time delay to the model can generate various bifurcations such as Hopf bifurcation, fold limit cycle bifurcation, Neimark-Sacker bifurcation of cycles, and period-doubling bifurcation, etc. Increasing the time delay can induce chaos by two routes: quasi-periodic route and period-doubling cascade.