From reversible to irreversible bistable switches via bifurcations in a gene regulatory network

The interplay of small, noncoding microRNAs (miRNAs), mRNAs and proteins plays crucial roles in almost all cellular processes. MiR-124, widely known as a memory-related miRNA, can regulate LTM by binding to the mRNA of CREB1 stimulated with 5-HT. In this paper, we establish a regulatory network mode...

Full description

Saved in:
Bibliographic Details
Published in:Physical biology 2020-07, Vol.17 (4), p.046001
Main Authors: Hao, Lijie, Yang, Zhuoqin, Shen, Danhong, Xing, Miaomiao
Format: Article
Language:English
Subjects:
Animals
Aplysia - drug effects
Aplysia - genetics
bifurcation analysis
bistable switches
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
Gene Regulatory Networks - drug effects
Humans
long-term facilitation
MicroRNAs - antagonists & inhibitors
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Models, Genetic
Neuronal Plasticity - drug effects
Neuronal Plasticity - genetics
Phosphorylation - drug effects
Serotonin - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The interplay of small, noncoding microRNAs (miRNAs), mRNAs and proteins plays crucial roles in almost all cellular processes. MiR-124, widely known as a memory-related miRNA, can regulate LTM by binding to the mRNA of CREB1 stimulated with 5-HT. In this paper, we establish a regulatory network model of CREB1 and miR-124 stimulated by 5-HT, in which miR-124 inhibits CREB1, which in turn enhances miR-124. Our model validates three protocols based on 5-HT in experiments on the induction of LTM in Aplysia. A steady-state analysis and numerical bifurcations of the abstracted system beyond memory formation, when the fast reaction has been in the equilibrium, can facilitate more abundant dynamical behaviors such as bistability and oscillation. The original system also exhibits bistability under appropriate feedback strengths, which is relevant to the mechanism of LTM formation. Furthermore, we specifically show a change in the transition from a reversible switch to an irreversible switch via bifurcations of the negative regulation of miR-124 on CREB1, which eventually maintains a high phosphorylated CREB1 level after initially elevated by 5-HT. These findings indicate that miR-124 provides an inhibitory constraint on long-term synaptic plasticity through the regulation of CREB1.
ISSN:1478-3975
1478-3967
1478-3975
DOI:10.1088/1478-3975/ab7bf5