Protosequences in human cortical organoids model intrinsic states in the developing cortex

Tjitse van der Molen, T.; Spaeth, A.; Chini, M.; Bartram, J.; Dendukuri, A.; Zhang, Z.; Bhaskaran-Nair, K.; Blauvelt, L. J.; Petzold, L. R.; Hansma, P. K.; Teodorescu, M.; Hierlemann, A.; Hengen, K. B.; Hanganu-Opatz, I. L.; Kosik, K. S.; Sharf, T.

doi:10.1101/2023.12.29.573646

bioRxiv · 10.1101/2023.12.29.573646

Protosequences in human cortical organoids model intrinsic states in the developing cortex

Tjitse van der Molen, T.·Spaeth, A.·Chini, M.·Bartram, J.·Dendukuri, A.·Zhang, Z.·Bhaskaran-Nair, K.·Blauvelt, L. J.·Petzold, L. R.·Hansma, P. K.·Teodorescu, M.·Hierlemann, A.·Hengen, K. B.·Hanganu-Opatz, I. L.·Kosik, K. S.·Sharf, T.

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Abstract

Neuronal firing sequences are thought to be the basic building blocks of neural coding and information broadcasting within the brain. However, when sequences emerge during neurodevelopment remains unknown. We demonstrate that structured firing sequences are present in spontaneous activity of human and murine brain organoids and ex vivo neonatal brain slices from the murine somatosensory cortex. We observed a balance between temporally rigid and flexible firing patterns that are emergent phenomena in human and murine brain organoids and early postnatal murine somatosensory cortex, but not in primary dissociated cortical cultures. Our findings suggest that temporal sequences do not arise in an experience-dependent manner, but are rather constrained by an innate preconfigured architecture established during neurogenesis. These findings highlight the potential for brain organoids to further explore how exogenous inputs can be used to refine neuronal circuits and enable new studies into the genetic mechanisms that govern assembly of functional circuitry during early human brain development.

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Tjitse van der Molen, T., Spaeth, A., Chini, M., Bartram, J., Dendukuri, A., Zhang, Z., Bhaskaran-Nair, K., Blauvelt, L. J., Petzold, L. R., Hansma, P. K., Teodorescu, M., Hierlemann, A., Hengen, K. B., Hanganu-Opatz, I. L., Kosik, K. S., Sharf, T.. 2023-12-30. Protosequences in human cortical organoids model intrinsic states in the developing cortex. https://doi.org/10.1101/2023.12.29.573646

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