Role of glial cells in synapse removal during circuit rewiring
Funded in: 2021, 2022, 2023
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Problem: Adult spinal cord has the capacity to partially repair itself
Target: Control by immune and glial cells during the remodeling
Goal: Shed light on the mechanisms at play during the control of axonal remodeling by glial cells
Following experimental incomplete SCI, the adult spinal cord has the capacity to partially repair itself and some level of spontaneous functional recovery can take place. Among others, this improvement is due to the rearrangement of axons connecting the brain to the spinal cord and the formation of new spinal relay circuits that bypass the lesion.
Specifically, the researchers could show such examples of those repair processes in which the corticospinal tract, one of the important descending motor tract in the spinal cord, sprouts short distance collaterals that form connections with interneurons in the spinal cord. To trigger spontaneous functional recovery, this remodeling needs to be tightly regulated at the spinal level by mechanisms that are still unknown. How are these new connections maintained and refined in the spinal cord following injury to form functional circuits is what the scientists want to uncover in this proposal. They will focus here on immune and glial cells such as microglia and astrocytes, as those cells have recently been identified as essential allies in the maintenance and refinement of neural networks during development and in adulthood. Thus, the aim of this research proposal is to determine if and how these immune and glial cells control the remodeling of the injured adult spinal cord. To this purpose, the neuroscientists will characterize the glial response in the injured spinal cord. They will then determine how those cells are controlling the maintenance and refinement of post-injury relay circuits and use a combination of RNA sequencing experiments and mouse genetic to tease out the mechanisms by which those cells can control the shaping of circuits post-injury. They will also determine how those glial cells influence sensorimotor recovery following spinal cord injury.
The researchers hope to shed light on the mechanisms at play during the control of axonal remodeling by glial cells following spinal cord injury. This might then be a basis for therapeutic strategies to shape remodeled circuits following spinal cord injury and enhance functional recovery.