How to switch on a complex brain: single-cell technologies to connect emergent nervous system activity with neural cell specification.

The functional complexity of the brain is established early in development as a result of feedback between cellular patterning events, establishment of gene regulatory networks and emergence of electrical connectivity. A key question is whether specific patterns of connectivity are required for higher-order cellular organization and function. It is not clear whether the establishment of neural connectivity follows a genetically and intrinsically determined path (nature), or whether the early (prenatal) network activity also functions as a feedback mechanism to fine tune higher-order brain organization and cell differentiation (nurture). It is also unknown whether there is an evolutionary 'universal logic' to the appearance and patterns of early brain activity and their link to cell specification.To tackle these fundamental questions, we need a multidisciplinary approach. Our consortium will for the first time be able to measure when, how and what type of early brain activity arises during development of human and Octopus vulgaris brain models and link this information to neural differentiation at the single-cell level. Our methods will deliver an unprecedented multidimensional platform to investigate (1) the mechanism behind many neurodevelopmental and psychiatric disorders, as well as (2) neuroregeneration processes in a highly innovative manner.

Keywords:single-cell genomics, organoids, multi-electrode arrays, human neurodevelopment, Octopus vulgaris, neural network activity

Disciplines:Single-cell data analysis, Transcriptomics, Semiconductor devices, nanoelectronics and technology, Organ engineering, Developmental neuroscience