title: Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells.
abstract: 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.
authors.affiliation: Gene 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 States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sternfeld
authors.affiliation: Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hinckley
authors.affiliation: Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Niall J
authors.initials: NJ
authors.lastname: Moore
authors.affiliation: Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Pankratz
authors.affiliation: Gene 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.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Hilde
authors.affiliation: Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Driscoll
authors.affiliation: Gene 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 States.
authors.forename: Marito
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Gene 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 States.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Amin
authors.affiliation: Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Dario
authors.initials: D
authors.lastname: Bonanomi
authors.affiliation: Gene 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 States.
authors.forename: Wesley D
authors.initials: WD
authors.lastname: Gifford
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, United States.
authors.forename: Kamal
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Martyn
authors.initials: M
authors.lastname: Goulding
authors.affiliation: Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Samuel L
authors.identifier: 0000-0002-2142-166X
authors.initials: SL
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
keywords: cell biology; circuitoid; embryonic stem cells; excitatory-inhibitory balance; mouse; neuroscience; rhythmicity; synthetic network