Functional strengthening through synaptic scaling upon connectivity disruption in neuronal cultures

Identificador:  imarina:9381083

Handle: https://hdl.handle.net/20.500.11797/imarina9381083

Autors:  Estevez-Priego, Estefania; Teller, Sara; Granell, Clara; Arenas, Alex; Soriano, Jordi

Resum:
Author Summary Neuronal circuits exhibit homeostatic plasticity mechanisms to cope with perturbations or damage. A central mechanism is 'synaptic scaling,' a self-organized response in which the strength of neurons' excitatory synapses is adjusted to compensate for activity variations. Here we present experiments in which the excitatory connectivity of in vitro cortical networks is progressively weakened through chemical action. The spontaneous activity and effective connectivity of the whole network is monitored as degradation progresses, and the capacity of the network for broad information communication is quantified through the global efficiency. We observed that the network responded to the perturbation by strengthening the effective connectivity, reaching a hyperefficient state for moderate perturbations. The study proves the importance of 'synaptic scaling' as a driver for functional reorganization and network-wide resilience. An elusive phenomenon in network neuroscience is the extent of neuronal activity remodeling upon damage. Here, we investigate the action of gradual synaptic blockade on the effective connectivity in cortical networks in vitro. We use two neuronal cultures configurations-one formed by about 130 neuronal aggregates and another one formed by about 600 individual neurons-and monitor their spontaneous activity upon progressive weakening of excitatory connectivity. We report that the effective connectivity in all cultures exhibits a first phase of transient strengthening followed by a second phase of steady deterioration. We quantify these phases by measuring G(EFF), the global efficiency in processing network information. We term hyperefficiency the sudden strengthening of G(EFF) upon network deterioration, which increases by 20-50% depending on culture type. Relying on numerical simulations we reveal the role of synaptic scaling, an activity-dependent mechanism for synaptic plasticity, in counteracting the perturbative action, neatly reproducing the observed hyperefficiency. Our results demonstrate the importance of synaptic scaling as resilience mechanism.