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@ARTICLE{Groden:268513,
author = {Groden, Moritz and Moessinger, Hannah M and Schaffran,
Barbara and DeFelipe, Javier and Benavides-Piccione, Ruth
and Cuntz, Hermann and Jedlicka, Peter},
title = {{A} biologically inspired repair mechanism for neuronal
reconstructions with a focus on human dendrites.},
journal = {PLoS Computational Biology},
volume = {20},
number = {2},
issn = {1553-734X},
address = {San Francisco, Calif.},
publisher = {Public Library of Science},
reportid = {DZNE-2024-00259},
pages = {e1011267},
year = {2024},
abstract = {Investigating and modelling the functionality of human
neurons remains challenging due to the technical
limitations, resulting in scarce and incomplete 3D
anatomical reconstructions. Here we used a morphological
modelling approach based on optimal wiring to repair the
parts of a dendritic morphology that were lost due to
incomplete tissue samples. In Drosophila, where dendritic
regrowth has been studied experimentally using laser
ablation, we found that modelling the regrowth reproduced a
bimodal distribution between regeneration of cut branches
and invasion by neighbouring branches. Interestingly, our
repair model followed growth rules similar to those for the
generation of a new dendritic tree. To generalise the repair
algorithm from Drosophila to mammalian neurons, we
artificially sectioned reconstructed dendrites from mouse
and human hippocampal pyramidal cell morphologies, and
showed that the regrown dendrites were morphologically
similar to the original ones. Furthermore, we were able to
restore their electrophysiological functionality, as
evidenced by the recovery of their firing behaviour.
Importantly, we show that such repairs also apply to other
neuron types including hippocampal granule cells and
cerebellar Purkinje cells. We then extrapolated the repair
to incomplete human CA1 pyramidal neurons, where the
anatomical boundaries of the particular brain areas
innervated by the neurons in question were known.
Interestingly, the repair of incomplete human dendrites
helped to simulate the recently observed increased synaptic
thresholds for dendritic NMDA spikes in human versus mouse
dendrites. To make the repair tool available to the
neuroscience community, we have developed an intuitive and
simple graphical user interface (GUI), which is available in
the TREES toolbox (www.treestoolbox.org).},
keywords = {Humans / Mice / Animals / Dendrites: physiology / Neurons:
physiology / Pyramidal Cells: physiology / Hippocampus:
physiology / Drosophila / Mammals},
cin = {AG Bradke},
ddc = {610},
cid = {I:(DE-2719)1013002},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10917450},
pubmed = {pmid:38394339},
doi = {10.1371/journal.pcbi.1011267},
url = {https://pub.dzne.de/record/268513},
}