Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits

Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In Drosophila, in contrast, sister neurons with different levels of Notch expression (NotchON/NotchOFF) develop distinct identities and diverge...

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Main Authors: Saul Bello-Rojas, Martha W Bagnall
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-12-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/83680
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author Saul Bello-Rojas
Martha W Bagnall
author_facet Saul Bello-Rojas
Martha W Bagnall
author_sort Saul Bello-Rojas
collection DOAJ
description Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In Drosophila, in contrast, sister neurons with different levels of Notch expression (NotchON/NotchOFF) develop distinct identities and diverge into separate circuits. Notch-differentiated sister neurons have been observed in vertebrate spinal cord and cerebellum, but whether they integrate into shared or distinct circuits remains unknown. Here, we evaluate how sister V2a (NotchOFF)/V2b (NotchON) neurons in the zebrafish integrate into spinal circuits. Using an in vivo labeling approach, we identified pairs of sister V2a/b neurons born from individual Vsx1+ progenitors and observed that they have somata in close proximity to each other and similar axonal trajectories. However, paired whole-cell electrophysiology and optogenetics revealed that sister V2a/b neurons receive input from distinct presynaptic sources, do not communicate with each other, and connect to largely distinct targets. These results resemble the divergent connectivity in Drosophila and represent the first evidence of Notch-differentiated circuit integration in a vertebrate system.
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spelling doaj.art-9ad31aeba4f749269dbbd3de0a68c8982022-12-29T15:14:21ZengeLife Sciences Publications LtdeLife2050-084X2022-12-011110.7554/eLife.83680Clonally related, Notch-differentiated spinal neurons integrate into distinct circuitsSaul Bello-Rojas0https://orcid.org/0000-0002-8090-9577Martha W Bagnall1https://orcid.org/0000-0003-2102-6165Department of Neuroscience, Washington University in St. Louis, St. Louis, United StatesDepartment of Neuroscience, Washington University in St. Louis, St. Louis, United StatesShared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In Drosophila, in contrast, sister neurons with different levels of Notch expression (NotchON/NotchOFF) develop distinct identities and diverge into separate circuits. Notch-differentiated sister neurons have been observed in vertebrate spinal cord and cerebellum, but whether they integrate into shared or distinct circuits remains unknown. Here, we evaluate how sister V2a (NotchOFF)/V2b (NotchON) neurons in the zebrafish integrate into spinal circuits. Using an in vivo labeling approach, we identified pairs of sister V2a/b neurons born from individual Vsx1+ progenitors and observed that they have somata in close proximity to each other and similar axonal trajectories. However, paired whole-cell electrophysiology and optogenetics revealed that sister V2a/b neurons receive input from distinct presynaptic sources, do not communicate with each other, and connect to largely distinct targets. These results resemble the divergent connectivity in Drosophila and represent the first evidence of Notch-differentiated circuit integration in a vertebrate system.https://elifesciences.org/articles/83680spinal cordclonal relationshipsNotchmotor circuit
spellingShingle Saul Bello-Rojas
Martha W Bagnall
Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits
eLife
spinal cord
clonal relationships
Notch
motor circuit
title Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits
title_full Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits
title_fullStr Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits
title_full_unstemmed Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits
title_short Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits
title_sort clonally related notch differentiated spinal neurons integrate into distinct circuits
topic spinal cord
clonal relationships
Notch
motor circuit
url https://elifesciences.org/articles/83680
work_keys_str_mv AT saulbellorojas clonallyrelatednotchdifferentiatedspinalneuronsintegrateintodistinctcircuits
AT marthawbagnall clonallyrelatednotchdifferentiatedspinalneuronsintegrateintodistinctcircuits