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Stadtman Investigator

Ariel Levine, M.D., Ph.D.

Spinal Circuits and Plasticity Unit

Spinal Circuits and Plasticity Unit (SCPU)
Building 35 Room 2B-1002
35 Convent Drive MSC3702
Bethesda MD 20892
Office: 301-402-6935
Lab: 301-402-6935
Fax: 301-496-4276

Dr. Levine received an undergraduate degree in biology from Brandeis University in 2000, a Ph.D. from The Rockefeller University in 2008, and an M.D. from Cornell University in 2009. During her graduate research with Dr. Ali Brivanlou, she studied the role of TGF-β signaling during embryonic development. Dr. Levine did postdoctoral research with Dr. Samuel Pfaff at The Salk Institute, where she identified a novel population of spinal neurons that encode “motor synergies” – modular neural programs for simple movements that are thought to underlie a wide variety of common behaviors. She was an Associate Member of the Reeve Foundation Consortium and a Fellow of the George Hewitt Foundation. She joined NINDS in 2015 where her lab studies how the molecules, neurons, and circuits of the spinal cord mediate normal behavior and learn.

We seek to understand how the molecules, cells, and circuits of the spinal cord mediate normal behavior, and how they change and adapt to allow learning. Far from being a passive relay between the brain and body, the spinal cord constantly integrates cues from the cortex, the brainstem, and sensory neurons, as well as other sources, and it ultimately transforms these cues into behavior. Further, the circuits of the spinal cord are dynamic. They learn in response to changes in incoming information. This happens during development, maturation, and in the adult animal.

We recently discovered a population of spinal neurons that directly receive cortical and sensory inputs and in turn, directly target the spinal motorneurons. Stimulating small clusters of neurons within this molecularly-defined population is sufficient to drive coordinated activation of multiple motor groups. This simple response may represent a “motor synergy” – modular motor programs that are hypothesized to be the core building blocks of our most common movements.

Now, we want to know: How are simple motor programs encoded? How are new motor programs or sensory responses learned by the spinal cord? And in the long term, can we use this knowledge to improve recovery for patients with stroke and spinal cord injury? With the mouse as our model system, we are using novel genetic tools, cutting-edge molecular analysis, and sophisticated behavioral analysis to explore the mechanisms of mammalian spinal cord function and plasticity.

Spinal neurons in the pre-motor network controlling the gastrocnemius (calf) muscle, color-coded by depth from the dorsal surface.

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  • Courtney Dobrott
    Post baccalaureate IRTA Fellow

  • Li Li, M.S.
    Animal Biologist

  • Kaya Matson
    Graduate Student
    NIH-Johns Hopkins University Graduate Partnership

  • Anupama Sathyamurthy, Ph.D.
    Postdoctoral Fellow

  • 1) Courtney IDobrottAnupamaSathyamurthyAriel JLevine (2019)
  • Decoding cell type diversity within the spinal cord
  • Current Opinion in Physiology, 8, 1-6
  • 2) Matson KJE, Sathyamurthy A, Johnson KR, Kelly MC, Kelley MW, Levine AJ (2018)
  • Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing.
  • Journal of Visualized Experiments
  • 3) Hayashi, M; Hinckley, CA; Driscoll, SP; Moore, NJ; Levine, AJ; Hilde, KL; Sharma, K; Pfaff, SL (2018)
  • Graded arrays of spinal and supraspinal V2a interneuron subtypes underlie forelimb and hindlimb motor control
  • Neuron, 97, 869-884
  • 4) Sathyamurthy, A*; Johnson, KR*; Matson, KEJ; Li, Li; Ryba, AR; Bergman, TB; Dobrott, CI; Kelly, MC; Kelley, MW; Levine, AJ (2018)
  • Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity During Behavior
  • Cell Reports, 22, 2216-2225
  • 5) Hilde, KL; Levine, AJ; Hinckley, CA; Hayashi, M; Montgomery, JM; Gullo, M; Driscoll, SP; Grosschedl, R; Kohwi, Y; Kohwi-Shigematsu, T; Pfaff, SL. (2016)
  • Satb2 is required for the development of a spinal exteroceptive microcircuit that modulates limb position.
  • Neuron, 91, 763-776
  • 6) Pawar, K; Cummings, B; Thomas, A; Shea, L; Levine, A; Pfaff, S; Anderson, A (2015)
  • Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: association with recovery of forelimb function
  • Biomaterials, 65, 1-12
  • 7) Levine, AJ*, Hinckley, CA*, Hilde, KL, Driscoll, SP, Poon, TH, Montgomery, JM, Pfaff, SL (2014)
  • Identification of a cellular node for motor control pathways
  • Nature Neuroscience, 17, 586:593. *equal contribution
  • 8) Levine, AJ; Lewallen KA; Pfaff SL (2012)
  • Spatial organization of cortical and spinal neurons controlling motor behavior
  • Current Opinions in Neurobiology, 22, 812-21
  • 9) Levine, AJ; Levine, ZJ; Brivanlou, AH (2009)
  • GDF-3 is a BMP inhibitor that can activate Nodal signaling only at very high doses
  • Developmental Biology , 325, 43-8
  • 10) Levine, AJ and Brivanlou, AH. (2008)
  • Molecular Basis of Pluripotency.
  • chapter in “Principles of Regenerative Medicine.” Ed Atala, A; Lanza, R. Academic Press, pp 118-127. ISBN 978-0-12-369410-2.
  • 11) Levine, AJ and Brivanlou, AH (2007)
  • Proposal of a Model of Mammalian Neural Induction
  • Developmental Biology, 308, 247-256
  • 12) Levine, AJ and Brivanlou, AH (2006)
  • GDF-3, a BMP inhibitor, regulates cell fate in stem cells and early embryos
  • Development, 133, 209-216
  • 13) Levine, AJ and Brivanlou, AH (2006)
  • GDF3 at the Crossroads of TGF-B Signaling
  • Cell Cycle , 5, 1069-1073
  • 14) James, D; Levine, AJ; Besser, D; Hemmati-Brivanlou, A (2005)
  • TGF-ß/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells
  • Development , 132, 1273-1282
  • 15) Levine, AJ; Munoz-Sanjuan, I; Bell, E; North, AJ; Brivanlou, AH (2003)
  • ) Fluorescent labeling of endothelial cells allows in vivo, continuous characterization of the vascular development of Xenopus laevis
  • Developmental Biology , 254, 50-67
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