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000268513 1001_ $$00000-0002-6851-2868$$aGroden, Moritz$$b0
000268513 245__ $$aA biologically inspired repair mechanism for neuronal reconstructions with a focus on human dendrites.
000268513 260__ $$aSan Francisco, Calif.$$bPublic Library of Science$$c2024
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000268513 520__ $$aInvestigating 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).
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000268513 650_2 $$2MeSH$$aHumans
000268513 650_2 $$2MeSH$$aMice
000268513 650_2 $$2MeSH$$aAnimals
000268513 650_2 $$2MeSH$$aDendrites: physiology
000268513 650_2 $$2MeSH$$aNeurons: physiology
000268513 650_2 $$2MeSH$$aPyramidal Cells: physiology
000268513 650_2 $$2MeSH$$aHippocampus: physiology
000268513 650_2 $$2MeSH$$aDrosophila
000268513 650_2 $$2MeSH$$aMammals
000268513 7001_ $$00000-0002-3012-0017$$aMoessinger, Hannah M$$b1
000268513 7001_ $$0P:(DE-2719)2811123$$aSchaffran, Barbara$$b2$$udzne
000268513 7001_ $$aDeFelipe, Javier$$b3
000268513 7001_ $$aBenavides-Piccione, Ruth$$b4
000268513 7001_ $$00000-0001-5445-0507$$aCuntz, Hermann$$b5
000268513 7001_ $$aJedlicka, Peter$$b6
000268513 773__ $$0PERI:(DE-600)2193340-6$$a10.1371/journal.pcbi.1011267$$gVol. 20, no. 2, p. e1011267 -$$n2$$pe1011267$$tPLoS Computational Biology$$v20$$x1553-734X$$y2024
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