Interlinked dual-time feedback loops can enhance robustness to stochasticity and persistence of memory.

Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular Ca2+ release. Recent studies with simplified models have identified two advantages of coupling fast and slow feedback loops. This dual-time structure enables a fast response while enhancing resistances of responses and bistability to stimulus noise. We now find that (1) the dual-time structure similarly confers resistance to internal noise due to molecule number fluctuations, and (2) model variants with altered coupling, which better represent some specific biochemical systems, share all the above advantages. We also develop a similar bistable model with coupling of a fast autoactivation loop to a slow loop. This model\u27s topology was suggested by positive feedback proposed to play a role in long-term synaptic potentiation (LTP). The advantages of fast response and noise resistance are also present in this autoactivation model. Empirically, LTP develops resistance to reversal over approximately 1h . The model suggests this resistance may result from increased amounts of synaptic kinases involved in positive feedback

Autaptic excitation contributes to bistability and rhythmicity in the neural circuit for feeding in Aplysia

The feeding circuit in Aplysia is a useful model system for studying the neuronal bases of cognitive functions such as sensory processing, generation of behavior, motivation, decision making, learning, and memory [1,2]. The goals of the present study are to develop a biologically-realistic model of the feeding circuit and to investigate the ways in which component processes contribute to circuit function. To begin, we developed a model of the central pattern generator (CPG) that mediates rhythmicity in the feeding circuit (Fig. ​(Fig.1A).1A). Simulations indicated that two positive-feedback loops (the B31 autapse and the synaptic interactions between B31 and B63) introduced bistability into the membrane potential of the B31 soma (Figures ​(Figures1B,1B, 1C1). In addition, simulations indicated that this plateau-like potential was the ‘deciding factor’ for initiating rhythmic activity (Fig. ​(Fig.1C).1C). Simulations also helped identify features of the model that warrant further empirical investigation; e.g., the simulated amplitude of the plateau-like potential was less than empirical observations