Functional strengthening through synaptic scaling upon connectivity disruption in neuronal cultures

Netw Neurosci. 2020 Dec 1;4(4):1160-1180. doi: 10.1162/netn_a_00156. eCollection 2020.

Abstract

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 GEFF, the global efficiency in processing network information. We term hyperefficiency the sudden strengthening of GEFF 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.

Keywords: CNQX; Calcium imaging; Effective connectivity; Functional organization; Global efficiency; Neuronal cultures; Synaptic scaling.