[en] The mouse cortex is a canonical model for studying how functional neural networks emerge, yet it remains unclear which topological features arise from intrinsic cellular organization versus sensory input. Mouse forebrain organoids provide a powerful system to investigate these intrinsic mechanisms. We generated dorsal (DF) and ventral (VF) forebrain organoids from mouse pluripotent stem cells and tracked their development using longitudinal electrophysiology. DF organoids showed progressively stronger network-wide correlations, while VF organoids developed more refined activity patterns with enhanced small-world topology and increased modular organization. Both organoid types form small-world networks, but their topological organization differs. These differences emerge without extrinsic inputs and correlate with Pvalb+ interneuron enrichment in VF organoids. Our findings demonstrate how cellular composition influences neural circuit self-organization, establishing mouse forebrain organoids as a tractable platform to study cortical network architecture.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Hernandez, Sebastian; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Electrical and Computer Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Schweiger, Hunter E; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Cline, Isabel; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Kaurala, Gregory A; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Robbins, Ash; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Electrical and Computer Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Solis, Daniel; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Vera-Choqqueccota, Samira; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Geng, Jinghui; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Electrical and Computer Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
van der Molen, Tjitse; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA
Reyes, Francisco; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Biotechnology Program, Berkeley City College, Berkeley, CA 94704, USA
Asogwa, Chinweike Norman; Department of Molecular, Cellular and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Voitiuk, Kateryna; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Electrical and Computer Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Chini, Mattia ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Rolandi, Marco; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Electrical and Computer Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Salama, Sofie R; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Colquitt, Bradley M; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Sharf, Tal; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Haussler, David; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Teodorescu, Mircea; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Electrical and Computer Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address: mteodore@ucsc.edu
Mostajo-Radji, Mohammed A; Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address: mmostajo@ucsc.edu
NINDS - National Institute of Neurological Disorders and Stroke NHGRI - National Human Genome Research Institute Brain and Behavior Research Foundation NIMH - National Institute of Mental Health UCLA - University of California, Los Angeles NSF - National Science Foundation
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