PT  - JOURNAL ARTICLE
AU  - S. Grade
AU  - J. Thomas
AU  - Y. Zarb
AU  - M. Thorwirth
AU  - Karl-Klaus Conzelmann
AU  - Stefanie M. Hauck
AU  - Magdalena Götz
TI  - Brain injury environment critically influences the connectivity of transplanted neurons
AID  - 10.1101/2021.12.13.472270
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.13.472270
4099  - http://biorxiv.org/content/early/2021/12/14/2021.12.13.472270.short
4100  - http://biorxiv.org/content/early/2021/12/14/2021.12.13.472270.full
AB  - Cell transplantation is a promising approach for the reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration and scar formation, as in traumatic brain injury (TBI). To elucidate this, we transplanted cells from the embryonic mouse cerebral cortex into TBI-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative connectomics unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact and inflamed brain, versus exuberant after trauma. In the latter, excessive synapse pruning follows the initial overshoot of connectivity resulting in only a few connections left. Proteomic profiling identifies candidate molecules involved in the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits.Teaser Neuronal grafts in a brain area affected by trauma receive excessive yet mostly vulnerable inputs from host circuits.Competing Interest StatementThe authors have declared no competing interest.