Analog Signaling With the "Digital" Molecular Switch CaMKII

作     者：Clarke, Stephen E. 

作者机构：Stanford Univ Dept Neurosurg Dept Bioengn Stanford CA 94305 USA 

出 版 物：《FRONTIERS IN COMPUTATIONAL NEUROSCIENCE》 (Front. Comput. Neurosci.)

年 卷 期：2018年第12卷

页      面：92页

核心收录：

基　　金：National Sciences and Engineering Research Council of Canada Canadian Institute of Health Research 

主　　题：molecular switches frequency coding stochastic resonance cellular computation CaMKII synaptic plasticity burst detection hill function 

摘      要：Molecular switches, such as the protein kinase CaMKII, play a fundamental role in cell signaling by decoding inputs into either high or low states of activity;because the high activation state can be turned on and persist after the input ceases, these switches have earned a reputation as digital. Although this on/off, binary perspective has been valuable for understanding long timescale synaptic plasticity, accumulating experimental evidence suggests that the CaMKII switch can also control plasticity on short timescales. To investigate this idea further, a non-autonomous, nonlinear ordinary differential equation, representative of a general bistable molecular switch, is analyzed. The results suggest that switch activity in regions surrounding either the high- or low-stable states of activation could act as a reliable analog signal, whose short timescale fluctuations relative to equilibrium track instantaneous input frequency. The model makes intriguing predictions and is validated against previous work demonstrating its suitability as a minimal representation of switch dynamics;in combination with existing experimental evidence, the theory suggests a multiplexed encoding of instantaneous frequency information over short timescales, with integration of total activity over longer timescales.