Temporal dynamics of neocortical development in organotypic mouse brain cultures: a comprehensive analysis

Bak, Aniella, Schmied, Katharina, Jakob, Morten L., Bedogni, Francesco, Squire, Olivia A., Gittel, Birgit, Jesinghausen, Maik, Schünemann, Kerstin D., Weber, Yvonne, Kampa, Björn, van Loo, Karen M. J. and Koch, Henner 2024. Temporal dynamics of neocortical development in organotypic mouse brain cultures: a comprehensive analysis. Journal of Neurophysiology 132 (3) , pp. 1038-1055. 10.1152/jn.00178.2024

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Abstract

Murine organotypic brain slice cultures have been widely used in neuroscientific research and are offering the opportunity to study neuronal function under normal and disease conditions. Despite the broad application, the mechanisms governing the maturation of immature cortical circuits in vitro are not well understood. In this study, we present a detailed investigation into the development of the neocortex in vitro. Using a holistic approach, we studied organotypic whole hemisphere brain slice cultures from postnatal mice and tracked the development of the somatosensory area over a 5-wk period. Our analysis revealed the maturation of passive and active intrinsic properties of pyramidal cells together with their morphology, closely resembling in vivo development. Detailed multielectrode array (MEA) electrophysiological assessments and RNA expression profiling demonstrated stable network properties by 2 wk in culture, followed by the transition of spontaneous activity toward more complex patterns including high-frequency oscillations. However, culturing weeks 4 and 5 exhibited increased variability and initial signs of neuronal loss, highlighting the importance of considering developmental stages in experimental design. This comprehensive characterization is vital for understanding the temporal dynamics of the neocortical development in vitro, with implications for neuroscientific research methodologies, particularly in the investigation of diseases such as epilepsy and other neurodevelopmental disorders.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Physiological Society
ISSN:	0022-3077
Date of First Compliant Deposit:	17 October 2024
Last Modified:	17 Oct 2024 10:45
URI:	https://orca.cardiff.ac.uk/id/eprint/172968

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