Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease

Niklas Schwarz, Betül Uysal, Marc Welzer, Jacqueline C. Bahr, Nikolas Layer, Heidi Löffler, Kornelijus Stanaitis, Harshad Pa, Yvonne G. Weber, Ulrike Bs Hedrich, J. rgen B. Honegger, Angelos Skodras, Albert J. Becker, Thomas V. Wuttke, Henner Koch

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling 'high throughput' fluorescence-mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro. This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry.
Original languageEnglish
JournaleLife
Volume8
DOIs
Publication statusPublished - 1 Sep 2019
Externally publishedYes

Cite this

Schwarz, N., Uysal, B., Welzer, M., Bahr, J. C., Layer, N., Löffler, H., ... Koch, H. (2019). Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease. eLife, 8. https://doi.org/10.7554/eLife.48417