Activity-dependent switches between dynamic regimes of extracellular matrix expression

Autoři: Ivan Lazarevich aff001;  Sergey Stasenko aff001;  Maiya Rozhnova aff001;  Evgeniya Pankratova aff001;  Alexander Dityatev aff003;  Victor Kazantsev aff001
Působiště autorů: Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russia aff001;  École Normale Supérieure, Paris Sciences et Lettres University, Laboratoire de Neurosciences Cognitives, Group for Neural Theory, Paris, France aff002;  Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases, Magdeburg, Germany aff003;  Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany aff004;  Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227917


Experimental studies highlight the important role of the extracellular matrix (ECM) in the regulation of neuronal excitability and synaptic connectivity in the nervous system. In its turn, the neural ECM is formed in an activity-dependent manner. Its maturation closes the so-called critical period of neural development, stabilizing the efficient configurations of neural networks in the brain. ECM is locally remodeled by proteases secreted and activated in an activity-dependent manner into the extracellular space and this process is important for physiological synaptic plasticity. We ask if ECM remodeling may be exaggerated under pathological conditions and enable activity-dependent switches between different regimes of ECM expression. We consider an analytical model based on known mechanisms of interaction between neuronal activity and expression of ECM, ECM receptors and ECM degrading proteases. We demonstrate that either inhibitory or excitatory influence of ECM on neuronal activity may lead to the bistability of ECM expression, so two stable stationary states are observed. Noteworthy, only in the case when ECM has predominant inhibitory influence on neurons, the bistability is dependent on the activity of proteases. Excitatory ECM-neuron feedback influences may also result in spontaneous oscillations of ECM expression, which may coexist with a stable stationary state. Thus, ECM-neuronal interactions support switches between distinct dynamic regimes of ECM expression, possibly representing transitions into disease states associated with remodeling of brain ECM.

Klíčová slova:

Action potentials – Extracellular matrix – Neural networks – Neuronal plasticity – Neurons – Proteases – System stability – Neural homeostasis


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2020 Číslo 1