Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells
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
Affiliations
Matthew J Sternfeld
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
Christopher A Hinckley
Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
Niall J Moore
Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
Matthew T Pankratz
Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
Kathryn L Hilde
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
Shawn P Driscoll
Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
Marito Hayashi
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
Neal D Amin
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
Dario Bonanomi
Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
Wesley D Gifford
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
Kamal Sharma
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, United States
Martyn Goulding
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States
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.
