Search

The properties of complex networked systems arise from the interplay between the dynamics of their elements and the underlying topology. Thus, to understand their behavior, it is crucial to convene as much information as possible about their topological organization. However, in large systems, such as neuronal networks, the reconstruction of such topology is usually carried out from the information encoded in the dynamics on the network, such as spike train time series, and by measuring the transfer entropy between system elements. The topological information recovered by these methods does not necessarily capture the connectivity layout, but rather the causal flow of information between elements. New theoretical frameworks, such as Integrated Information Decomposition (Φ-ID), allow one to explore the modes in which information can flow between parts of a system, opening a rich landscape of interactions between network topology, dynamics, and information. Here, we apply Φ-ID on in silico and in vitro data to decompose the usual transfer entropy measure into different modes of information transfer, namely, synergistic, redundant, or unique. We demonstrate that the unique information transfer is the most relevant measure to uncover structural topological details from network activity data, while redundant information only introduces residual information for this application. Although the retrieved network connectivity is still functional, it captures more details of the underlying structural topology by avoiding to take into account emergent high-order interactions and information redundancy between elements, which are important for the functional behavior, but mask the detection of direct simple interactions between elements constituted by the structural network topology., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

We study the structural and dynamical consequences of damage in spatial neuronal networks. Inspired by real in vitro networks, we construct directed networks embedded in a two-dimensional space and follow biological rules for designing the wiring of the system. As a result, synthetic cultures display strong metric correlations similar to those observed in real experiments. In its turn, neuronal dynamics is incorporated through the Izhikevich model adopting the parameters derived from observation in real cultures. We consider two scenarios for damage, targeted attacks on those neurons with the highest out-degree and random failures. By analyzing the evolution of both the giant connected component and the dynamical patterns of the neurons as nodes are removed, we observe that network activity halts for a removal of 50% of the nodes in targeted attacks, much lower than the 70% node removal required in the case of random failures. Notably, the decrease of neuronal activity is not gradual. Both damage scenarios portray "boosts" of activity just before full silencing that are not present in equivalent random (Erdös-Rényi) graphs. These boosts correspond to small, spatially compact subnetworks that are able to maintain high levels of activity. Since these subnetworks are absent in the equivalent random graphs, we hypothesize that metric correlations facilitate the existence of local circuits sufficiently integrated to maintain activity, shaping an intrinsic mechanism for resilience.

We introduce a novel random field Ising model, grounded on experimental observations, to assess the importance of metric correlations in cortical circuits in vitro. Metric correlations arise from both the finite axonal length and the heterogeneity in the spatial arrangement of neurons. The experiments consider the response of neuronal cultures to an external electric stimulation for a gradually weaker connectivity strength between neurons, and in cultures with different spatial configurations. The model can be analytically solved in the metric-free, mean-field scenario. The presence of metric correlations precipitates a strong deviation from the mean field. Null models of the same networks that preserve the distribution of connections recover the mean field. Our results show that metric-inherited correlations in spatial networks dominate the connectivity blueprint, mask the actual distribution of connections, and may emerge as the asset that shapes network dynamics.

Induced pluripotent stem cell (iPSC) technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks.

The neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been shown to promote excitatory and inhibitory synapse development. However, a quantitative analysis of their influence on connectivity has proven in general difficult to achieve. In this work we use a novel experimental approach based on percolation concepts that provides a quantification of the average number of connections per neuron. In combination with electrophysiological measurements, we characterize the changes in network connectivity induced by BDNF and NT-3 in rat hippocampal cultures. We show that, on the one hand, BDNF and NT-3 accelerate the maturation of connectivity in the network by about 17 h. On the other hand, BDNF and NT-3 increase the number of excitatory input connections by a factor of about two, but without modifying the number of inhibitory input connections. This scenario of a dominant effect on the excitation is supported by the analysis of spontaneous population bursts in cultures treated with either BDNF or NT-3, which show burst amplitudes that are insensitive to the blockade of inhibition. A leaky integrate-and-fire model reproduces the experimental results well.

We introduce an approach for the quantitative assessment of the connectivity in neuronal cultures, based on the statistical mechanics of percolation on a graph. This allows us to monitor the development of the culture and to see the emergence of connectivity in the network. The culture becomes fully connected at a time equivalent to the expected time of birth. The spontaneous bursting activity that characterizes cultures develops in parallel with the connectivity. The average number of inputs per neuron can be quantitatively determined in units of m(0), the number of activated inputs needed to excite the neuron. For m(0) approximately 15 we find that hippocampal neurons have on average approximately 60-120 inputs, whereas cortical neurons have approximately 75-150, depending on neuronal density. The ratio of excitatory to inhibitory neurons is determined by using the GABA(A) antagonist bicuculine. This ratio changes during development and reaches the final value at day 7-8, coinciding with the expected time of the GABA switch. For hippocampal cultures the inhibitory cells comprise approximately 30% of the neurons in the culture whereas for cortical cultures they are approximately 20%. Such detailed global information on the connectivity of networks in neuronal cultures is at present inaccessible by any electrophysiological or other technique.

We study living neural networks by measuring the neurons' response to a global electrical stimulation. Neural connectivity is lowered by reducing the synaptic strength, chemically blocking neurotransmitter receptors. We use a graph-theoretic approach to show that the connectivity undergoes a percolation transition. This occurs as the giant component disintegrates, characterized by a power law with an exponent beta approximately or = 0.65. Beta is independent of the balance between excitatory and inhibitory neurons and indicates that the degree distribution is Gaussian rather than scale free.