Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells

Flexible neural networks, such as the interconnected spinal neurons that control distinct motor actions, can switch their activity to produce different behaviors. Both excitatory (E) and inhibitory (I) spinal neurons are necessary for motor behavior, but the influence of recruiting different ratios...

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Main Authors: Matthew J Sternfeld, Christopher A Hinckley, Niall J Moore, Matthew T Pankratz, Kathryn L Hilde, Shawn P Driscoll, Marito Hayashi, Neal D Amin, Dario Bonanomi, Wesley D Gifford, Kamal Sharma, Martyn Goulding, Samuel L Pfaff
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-02-01
Series:eLife
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Online Access:https://elifesciences.org/articles/21540
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author Matthew J Sternfeld
Christopher A Hinckley
Niall J Moore
Matthew T Pankratz
Kathryn L Hilde
Shawn P Driscoll
Marito Hayashi
Neal D Amin
Dario Bonanomi
Wesley D Gifford
Kamal Sharma
Martyn Goulding
Samuel L Pfaff
author_facet Matthew J Sternfeld
Christopher A Hinckley
Niall J Moore
Matthew T Pankratz
Kathryn L Hilde
Shawn P Driscoll
Marito Hayashi
Neal D Amin
Dario Bonanomi
Wesley D Gifford
Kamal Sharma
Martyn Goulding
Samuel L Pfaff
author_sort Matthew J Sternfeld
collection DOAJ
description Flexible neural networks, such as the interconnected spinal neurons that control distinct motor actions, can switch their activity to produce different behaviors. Both excitatory (E) and inhibitory (I) spinal neurons are necessary for motor behavior, but the influence of recruiting different ratios of E-to-I cells remains unclear. We constructed synthetic microphysical neural networks, called circuitoids, using precise combinations of spinal neuron subtypes derived from mouse stem cells. Circuitoids of purified excitatory interneurons were sufficient to generate oscillatory bursts with properties similar to in vivo central pattern generators. Inhibitory V1 neurons provided dual layers of regulation within excitatory rhythmogenic networks - they increased the rhythmic burst frequency of excitatory V3 neurons, and segmented excitatory motor neuron activity into sub-networks. Accordingly, the speed and pattern of spinal circuits that underlie complex motor behaviors may be regulated by quantitatively gating the intra-network cellular activity ratio of E-to-I neurons.
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spelling doaj.art-10ac875644e74cddb906b2d1a978f50c2022-12-22T02:05:29ZengeLife Sciences Publications LtdeLife2050-084X2017-02-01610.7554/eLife.21540Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cellsMatthew J Sternfeld0Christopher A Hinckley1Niall J Moore2Matthew T Pankratz3Kathryn L Hilde4Shawn P Driscoll5Marito Hayashi6Neal D Amin7Dario Bonanomi8Wesley D Gifford9Kamal Sharma10Martyn Goulding11Samuel L Pfaff12https://orcid.org/0000-0002-2142-166XGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States; Biological Sciences Graduate Program, University of California, San Diego, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States; Biological Sciences Graduate Program, University of California, San Diego, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, United States; Medical Scientist Training Program, University of California, San Diego, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States; Medical Scientist Training Program, University of California, San Diego, La Jolla, United States; Neurosciences Graduate Program, University of California, San Diego, La Jolla, United StatesDepartment of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, United StatesMolecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United StatesGene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesFlexible neural networks, such as the interconnected spinal neurons that control distinct motor actions, can switch their activity to produce different behaviors. Both excitatory (E) and inhibitory (I) spinal neurons are necessary for motor behavior, but the influence of recruiting different ratios of E-to-I cells remains unclear. We constructed synthetic microphysical neural networks, called circuitoids, using precise combinations of spinal neuron subtypes derived from mouse stem cells. Circuitoids of purified excitatory interneurons were sufficient to generate oscillatory bursts with properties similar to in vivo central pattern generators. Inhibitory V1 neurons provided dual layers of regulation within excitatory rhythmogenic networks - they increased the rhythmic burst frequency of excitatory V3 neurons, and segmented excitatory motor neuron activity into sub-networks. Accordingly, the speed and pattern of spinal circuits that underlie complex motor behaviors may be regulated by quantitatively gating the intra-network cellular activity ratio of E-to-I neurons.https://elifesciences.org/articles/21540circuitoidsynthetic networkexcitatory-inhibitory balanceembryonic stem cellsrhythmicity
spellingShingle Matthew J Sternfeld
Christopher A Hinckley
Niall J Moore
Matthew T Pankratz
Kathryn L Hilde
Shawn P Driscoll
Marito Hayashi
Neal D Amin
Dario Bonanomi
Wesley D Gifford
Kamal Sharma
Martyn Goulding
Samuel L Pfaff
Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells
eLife
circuitoid
synthetic network
excitatory-inhibitory balance
embryonic stem cells
rhythmicity
title Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells
title_full Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells
title_fullStr Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells
title_full_unstemmed Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells
title_short Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells
title_sort speed and segmentation control mechanisms characterized in rhythmically active circuits created from spinal neurons produced from genetically tagged embryonic stem cells
topic circuitoid
synthetic network
excitatory-inhibitory balance
embryonic stem cells
rhythmicity
url https://elifesciences.org/articles/21540
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