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Network and micro-circuitry development in human brain organoids

  • Francesca Puppo
    Affiliations
    Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, CA 92037, USA
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  • Alysson Renato Muotri
    Correspondence
    Correspondence to Dr. Alysson R. Muotri, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037,
    Affiliations
    Departments of Pediatrics and Cellular & Molecular Medicine, University of California San Diego, School of Medicine, Center for Academic Research and Training in Anthropogeny (CARTA), Kavli Institute for Brain and Mind, Archealization Center (ArchC), La Jolla, CA 92037, USA
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      One of the critical challenges of human neuron cultures is to keep them alive and healthy for as long as they need to transition from neural progenitor cells to mature neurons and neural networks. In brain organoids, human neurons grow isotropically in three directions, creating a more natural and supporting environment for development, which is reflected by the extended survival rate, the higher degree of structural complexity, the improved cellular, and molecular composition, and the maturing electrophysiological complexity. Several studies have shown that brain organoids can recapitulate critical aspects of the developing brain [
      • Trujillo C.A.
      • Muotri A.R.
      Brain Organoids and the Study of Neurodevelopment.
      ]. Taking advantage of recent advances in genetic technologies and transcriptomics, previous works provided a detailed characterization of cell types and developmental states within organoids. As the field has started witnessing exponential growth, functional analysis by means of electrophysiology studies has also become more frequently employed to identify the biophysical phenotype of the cell population [
      • Fair S.R.
      • Julian D.
      • Hartlaub A.M.
      • Pusuluri S.T.
      • Malik G.
      • Summerfied T.L.
      • Zhao G.
      • Hester A.B.
      • Ackerman W.E.
      • Hollingsworth E.W.
      • Ali M.
      • McElroy C.A.
      • Buhimschi I.A.
      Electrophysiological Maturation of Cerebral Organoids Correlates with Dynamic Morphological and Cellular Development.
      ]. However, the functional characterization of 3D in vitro cultures remains exceptionally challenging.
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