Cooperative stochastic binding and unbinding explain synaptic size dynamics and statistics
| Autor: | Naama Brenner, Lukas Geyrhofer, Aseel Shomar, Noam E. Ziv |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Basic premise Statistical methods Physiology Cooperativity Nervous System Synaptic Transmission Medicine and Health Sciences Nanotechnology Statistical physics lcsh:QH301-705.5 Mesoscopic Physics Physics Cerebral Cortex Neurons Mesoscopic physics Ecology Simulation and Modeling Condensed Matter Physics Postsynaptic membrane Electrophysiology Monte Carlo method Computational Theory and Mathematics Modeling and Simulation Physical Sciences Engineering and Technology Anatomy Research Article Statistical Distributions Protein Binding Models Neurological Biophysics Neurophysiology Statistics (mathematics) Neurotransmission Research and Analysis Methods Skewness Nanoclusters 03 medical and health sciences Cellular and Molecular Neuroscience Genetics Animals Particle Size Molecular Biology Scaling Ecology Evolution Behavior and Systematics Stochastic Processes Quantitative Biology::Neurons and Cognition Stochastic process Biology and Life Sciences Computational Biology Probability Theory Probability Distribution Rats 030104 developmental biology lcsh:Biology (General) Synapses Nanoparticles Mathematical and statistical techniques Mathematics Neuroscience |
| Zdroj: | PLoS Computational Biology PLoS Computational Biology, Vol 13, Iss 7, p e1005668 (2017) |
| ISSN: | 1553-7358 1553-734X |
| Popis: | Synapses are dynamic molecular assemblies whose sizes fluctuate significantly over time-scales of hours and days. In the current study, we examined the possibility that the spontaneous microscopic dynamics exhibited by synaptic molecules can explain the macroscopic size fluctuations of individual synapses and the statistical properties of synaptic populations. We present a mesoscopic model, which ties the two levels. Its basic premise is that synaptic size fluctuations reflect cooperative assimilation and removal of molecules at a patch of postsynaptic membrane. The introduction of cooperativity to both assimilation and removal in a stochastic biophysical model of these processes, gives rise to features qualitatively similar to those measured experimentally: nanoclusters of synaptic scaffolds, fluctuations in synaptic sizes, skewed, stable size distributions and their scaling in response to perturbations. Our model thus points to the potentially fundamental role of cooperativity in dictating synaptic remodeling dynamics and offers a conceptual understanding of these dynamics in terms of central microscopic features and processes. Author summary Neurons communicate through specialized sites of cell–cell contact known as synapses. This vast set of connections is believed to be crucial for sensory processing, motor function, learning and memory. Experimental data from recent years suggest that synapses are not static structures, but rather dynamic assemblies of molecules that move in, out and between nearby synapses, with these dynamics driving changes in synaptic properties over time. Thus, in addition to changes directed by activity or other physiological signals, synapses also exhibit spontaneous changes that have particular dynamical and statistical signatures. Given the immense complexity of synapses at the molecular scale, how can one hope to understand the principles that govern these spontaneous changes and statistical signatures? Here we offer a mesoscopic modelling approach—situated between detailed microscopic and abstract macroscopic approaches—to advance this understanding. Our model, based on simplified biophysical assumptions, shows that spontaneous cooperative binding and unbinding of proteins at synaptic sites can give rise to dynamic and statistical signatures similar to those measured in experiments. Importantly, we find cooperativity to be indispensable in this regard. Our model thus offers a conceptual understanding of synaptic dynamics and statistical features in terms of a fundamental biological principle, namely cooperativity. |
| Databáze: | OpenAIRE |
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