Goal: 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. Ultimately, we hope to leverage novel findings in basic science to improve recovery for patients with stroke and spinal cord injury.
Background: The mammalian spinal cord is a remarkable system. It receives cues from the cortex, the brainstem, and other sources, and transforms these diverse inputs into behavior. 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. It is dynamic. Surprisingly, the circuits of the spinal cord learn in response to changes in incoming information. This happens during development, maturation, and in the adult animal.
We want to know: How are behaviors and new memories encoded within the mammalian spinal cord? What are the mechanisms of neural plasticity - from the control of gene expression to the re-wiring of circuits? And in the long term, can we use this knowledge to improve recovery for patients with stroke and spinal cord injury?
Spinal Cord Atlas and Activity Mapping: To provide a foundation for this work, we established a molecular and cellular atlas of the adult mouse spinal cord. We adapted a method for massively parallel single nucleus sequencing and characterized forty-nine cell types - oligodendrocytes and their precursors, astrocytes, microglia, vascular cells, meningeal cells, and forty-three diverse populations of neurons. Using nuclei instead of cells prevents experimental activation of cell stress pathways that turn on immediate early genes (IEGs), so our method yields a very low baseline level of IEGs. That allows us to probe the endogenous activity-induced gene expression signatures that follow neuronal activity and use sequencing to identify activated populations. Accordingly, we can overlay the activated neurons onto the single nucleus atlas and create an unbiased "map" of the cell-types associated with a defined behavior.