Functional strengthening through synaptic scaling upon connectivity disruption in neuronal cultures.

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.

Spontaneous Functional Recovery after Focal Damage in Neuronal Cultures.

Damage in biological neuronal networks triggers a complex functional reorganization whose mechanisms are still poorly understood. To delineate this reorganization process, here we investigate the functional alterations of in vitro rat cortical circuits following localized laser ablation. The analysis of the functional network configuration before and after ablation allowed us to quantify the extent of functional alterations and the characteristic spatial and temporal scales along recovery. We observed that damage precipitated a fast rerouting of information flow that restored network's communicability in about 15 min. Functional restoration was led by the immediate neighbors around trauma but was orchestrated by the entire network. Our in vitro setup exposes the ability of neuronal circuits to articulate fast responses to acute damage, and may serve as a proxy to devise recovery strategies in actual brain circuits. Moreover, this biological setup can become a benchmark to empirically test network theories about the spontaneous recovery in dynamical networks.

Impact of modular organization on dynamical richness in cortical networks.

As in many naturally formed networks, the brain exhibits an inherent modular architecture that is the basis of its rich operability, robustness, and integration-segregation capacity. However, the mechanisms that allow spatially segregated neuronal assemblies to swiftly change from localized to global activity remain unclear. Here, we integrate microfabrication technology with in vitro cortical networks to investigate the dynamical repertoire and functional traits of four interconnected neuronal modules. We show that the coupling among modules is central. The highest dynamical richness of the network emerges at a critical connectivity at the verge of physical disconnection. Stronger coupling leads to a persistently coherent activity among the modules, while weaker coupling precipitates the activity to be localized solely within the modules. An in silico modeling of the experiments reveals that the advent of coherence is mediated by a trade-off between connectivity and subquorum firing, a mechanism flexible enough to allow for the coexistence of both segregated and integrated activities. Our results unveil a new functional advantage of modular organization in complex networks of nonlinear units.

Magnetite-Amyloid-ß deteriorates activity and functional organization in an in vitro model for Alzheimer's disease.

The understanding of the key mechanisms behind human brain deterioration in Alzheimer' disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-ß peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role. To shed light on the action of magnetite and amyloid-ß in the deterioration of neuronal circuits, we investigated their capacity to alter spontaneous activity patterns in cultured neuronal networks. Using a versatile experimental platform that allows the parallel monitoring of several cultures, the activity in controls was compared with the one in cultures dosed with magnetite, amyloid-ß and magnetite-amyloid-ß complex. A prominent degradation in spontaneous activity was observed solely when amyloid-ß and magnetite acted together. Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-ß complex. Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

Emergence of assortative mixing between clusters of cultured neurons.

The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons (clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, as well as a rich-club core, which shapes a 'connectivity backbone' in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture.