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Abstract

Neural plasticity allows us to form new memories and learn new behaviours. After neurotrauma, it allows adaptation to and, to a limited extent, recovery of lost function. Even following severe injuries such as spinal cord injury (SCI), most of which spare some ascending and descending circuitry, there is a degree of functional restoration that reflects reorganization of remaining neural pathways. Understanding and exploiting mechanisms of spontaneous plasticity is an avenue to generating new approaches to a cure for SCI. To date, most of the experimental work on functional recovery following SCI has focused on descending projections that subserve voluntary movement and locomotion; however, these are initiated and informed by (and are thus dependent upon) sensory input from the body to the brain via “spinofugal” projections. Here I have exploited the developmental expression of Hoxb8, which is restricted to the spinal cord, to genetically label ascending projections to the cerebellum. A detailed anatomical analysis of four reporter lines identified many unexpected Hoxb8-lineage neuronal and non-neuronal cell types in targeted and untargeted transgenic strains, but because of the near-exclusive restriction of reporter expression to spinofugal projections, Hoxb8FlpOᵀᵈᵀ mice were selected as the best model for assessing the distribution of spinocerebellar projections and their possible structural plasticity. I used a cervical (C3) lateral hemisection model to document the natural history of sensorimotor performance over the first month following injury, employing established and novel behavioural measures. These revealed that many behavioural parameters changed spontaneously with time during the post-injury period, while several did not (i.e. were stable deficits), or did not change with injury at all. Since some of the behaviours which recovered (e.g. those which depend on grasp) normally require cerebellar function, I asked whether plasticity of spinocerebellar projections might have contributed. I found that at one month after hemisection, remaining spinocerebellar projections had increased in density (i.e. had sprouted), size, and content of presynaptic machinery, implicating these as possible substrates of functional recovery. I also identified transcriptomic changes in the partially-deafferented cerebellum expected as a consequence of axonal degeneration, and others which suggest how these might lead to spontaneous compensatory plasticity.