A multilayer network model of neuron-astrocyte populations in vitro reveals mGluR5 inhibition is protective following traumatic injury

Abstract

Astrocytes communicate bidirectionally with neurons, enhancing synaptic plasticity and promoting the synchronization of neuronal microcircuits. Despite recent advances in understanding neuron-astrocyte signaling, little is known about astrocytic modulation of neuronal activity at the population level, particularly in disease or following injury. We used high-speed calcium imaging of mixed cortical cultures in vitro to determine how population activity changes after disruption of glutamatergic signaling and mechanical injury. We constructed a multilayer network model of neuron-astrocyte connectivity, which captured distinct topology and response behavior from single cell type networks. mGluR5 inhibition decreased neuronal, but did not on its own disrupt functional connectivity or network topology. In contrast, injury increased the strength, clustering, and efficiency of neuronal but not astrocytic networks, an effect that was not observed in networks pre-treated with mGluR5 inhibition. Comparison of spatial and functional community structure revealed that functional connectivity is largely independent of spatial proximity at the microscale, but mechanical injury increased the spatial-functional correlation. Finally, we found that astrocyte segments of the same cell often belong to separate functional communities based on neuronal connectivity, suggesting that astrocyte segments function as independent entities. Our findings demonstrate the utility of multilayer network models for characterizing the multiscale connectivity of two distinct but functionally dependent cell populations.

A Review of Research on the Association between Neuron–Astrocyte Signaling Processes and Depressive Symptoms

“…In addition, on the one hand, astrocytes are stimulated to create glutamate as a result of the release of endocannabinoids from neurons, which allows them to communicate with neurons located further away [ 103 ]. On the other hand, ATP produced by astrocytes not only works as a bridge for communication between astrocytes and neurons, it also acts as a bridge for neurons to transmit information extrasynaptically [ 104 ] ( Figure 3 ). This implies that information may also be transmitted to far-off synapses through interactions between astrocytes and neurons.…”