Seeing the Forest and the Trees: Single Nucleus Sequencing in the Spinal Cord

To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. We sought to leverage the recent revolution in single cell transcriptional profiling to reveal the cell types of the adult mouse spinal cord and their activity. First, we adapted a robust strategy for massively parallel single nucleus RNA sequencing that can be used for complex central nervous system tissue without driving experimental changes in gene expression. Next, we created a molecular and cellular atlas of the adult mouse spinal cord. We identified and characterized forty-three neuronal populations that encompass dorsal, ventral, excitatory, and inhibitory cell types and include both previously known and novel populations. Finally, we used the dynamic transcriptional signature of neuronal activity to “map” activated neurons associated with a sensory response and a motor behavior. This approach can now be used to link single cell resolution to system wide changes and reveal gene the dynamic biological responses to behavior, injury, and disease.

Bio
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 postdoctoral research with Dr. Samuel Pfaff at The Salk Institute, 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 joined the National Institutes of Health in 2015 where her lab studies how the molecules, neurons, and circuits of the spinal cord mediate normal behavior and learn.