Functional Connectivity in Human-Derived Neurospheroids

Brain functions are performed through the joint actions of neurons, which interact through their afferent and efferent connections in an orchestrated manner. Investigating the connectivity processes arising in brain networks can provide important advances in basic as well as applied neuroscience. In this study, we present a brain-on-a-chip model based on two important features of the living brain: three-dimensionality and heterogeneity. We used neuronal networks derived from human-induced pluripotent stem cells (hiPSCs) and computed the functional connectivity properties of homogeneous (composed of excitatory neurons only) as well as heterogeneous (composed of both excitatory and inhibitory neurons) human-derived neurospheroids. We found that inhibition affected the topology of the neuronal cultures by increasing the number of connections, while both models exhibited small-world properties. This work has laid the foundation for future studies aimed at exploring connectivity-related impairments.