The spinal cord is the major link between the brain and the body. It receives cues from the cortex, the brainstem, and other sources, and transforms these diverse inputs into behavior. In addition, it is the primary relay point for sensory pathways from the body and constantly integrates multiple streams of information about body position, touch, and pain. We seek to understand how the diverse cell types of the spinal cord function together to mediate normal behavior. Ultimately, we hope to use this knowledge to improve recovery for patients with stroke and spinal cord injury. We are guided by three key questions:
What are the cell types of the mammalian spinal cord?
Using massively parallel single nucleus RNA sequencing, we established the first molecular and cellular atlas of the adult spinal cord. This work identified different organization of the dorsal and ventral regions of the spinal cord, revealed novel populations, and serves as an important reference to our field. In ongoing work, we use similar techniques to probe cell-type specific changes in different behaviors and in response to injury and disease. We also develop new computational approaches to analyze single cell spinal cord data.
How do specific spinal cord cell types contribute to behavior?
We use mouse genetics, cell type specific manipulations, and behavioral analysis to reveal how specific neuronal populations contribute to movement and to motor learning. In addition, we are interested in the molecular basis of neuronal diversity - how the unique molecular repertoire of each neuronal population serves its cellular and circuit functions.
How are spinal cord cells incorporated into central nervous system-wide circuits for motor control?
We study how descending pathways from different areas of the brain target specific spinal cord populations to help mediate coordinated movements. We recently defined the anatomy, function, and spinal targets of the cerebellospinal tract.
Spinal neurons in the pre-motor network controlling the gastrocnemius (calf) muscle, color-coded by depth from the dorsal surface.
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.
- Russ DE, Cross RBP, Li L, Koch SC, Matson KJE, Yadav A, Alkaslasi MR, Lee DI, Le Pichon CE, Menon V, Levine AJ. A harmonized atlas of mouse spinal cord cell types and their spatial organization. Nat Commun. 2021;12(1):5722.
- Sathyamurthy A, Barik A, Dobrott CI, Matson KJE, Stoica S, Pursley R, Chesler AT, Levine AJ. Cerebellospinal Neurons Regulate Motor Performance and Motor Learning. Cell Rep. 2020;31(6):107595.
- Skinnider MA, Squair JW, Kathe C, Anderson MA, Gautier M, Matson KJE, Milano M, Hutson TH, Barraud Q, Phillips AA, Foster LJ, La Manno G, Levine AJ, Courtine G. Cell type prioritization in single-cell data. Nat Biotechnol. 2021;39(1):30-34.
- Matson KJE, Sathyamurthy A, Johnson KR, Kelly MC, Kelley MW, Levine AJ. Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing. J Vis Exp. 2018;(140).
- Sathyamurthy A, Johnson KR, Matson KJE, Dobrott CI, Li L, Ryba AR, Bergman TB, Kelly MC, Kelley MW, Levine AJ. Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior. Cell Rep. 2018;22(8):2216-2225.
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This page was last updated on Wednesday, August 10, 2022