Recovery after a spinal cord injury often requires that axons restore synaptic connectivity with denervated targets several centimeters from the site of injury. Here we report that systemic artemin (ARTN) treatment promotes the regeneration of sensory axons to the brainstem after brachial dorsal root crush in adult rats. ARTN not only stimulates robust regeneration of large, myelinated sensory axons to the brainstem, but also promotes functional reinnervation of the appropriate target region, the cuneate nucleus. ARTN signals primarily through the RET tyrosine kinase, an interaction that requires the nonsignaling coreceptor GDNF family receptor (GFRα3). Previous studies reported limited GFRα3 expression on large sensory neurons, but our findings demonstrate that ARTN promotes robust regeneration of large, myelinated sensory afferents. Using a cell sorting technique, we demonstrate that GFRα3 expression is similar in myelinated and unmyelinated adult sensory neurons, suggesting that ARTN likely induces long-distance regeneration by binding GFRα3 and RET. Although ARTN is delivered for just 2 wk, regeneration to the brainstem requires more than 3 mo, suggesting that brief trophic support may initiate intrinsic growth programs that remain active until targets are reached. Given its ability to promote targeted functional regeneration to the brainstem, ARTN may represent a promising therapy for restoring sensory function after spinal cord injury.artemin | GFRα3 | regeneration | dorsal root crush | cuneate nucleus S pinal cord (SC) injury results in permanent paresis and paralysis, owing in large part to the failure of axons to regenerate. In the adult SC, axons do not regenerate because of myelin-and injury-associated inhibitory barriers and a limited intrinsic regenerative ability (1). Although there has been some success in removing extrinsic barriers and providing neurotrophic factors to promote functional regeneration over short distances (2-4), meaningful functional recovery requires that damaged axons regenerate and reconnect with their original targets, often centimeters away from the lesion. Studies in which damaged sensory axons were induced to regenerate to the brainstem have failed to show reestablishment of synapses (5). These findings cast doubt on whether sensory axons can regenerate functionally to the brainstem. Dorsal root (DR) crush provides a useful model for studying long-distance axon regeneration without affecting the architecture of the SC. Fine touch and proprioceptive neurons with cell bodies in the DR ganglion (DRG) provide monosynaptic input to neurons in the dorsal column nuclei. These neurons can be traced using transganglionic labeling methods and are easily studied electrophysiologically, making this an ideal injury model for investigating functional regeneration from the brachial SC to the brainstem.Previous studies demonstrated that a 2-wk systemic treatment with the neurotrophic factor artemin (ARTN) promotes topographically specific regeneration of both myelinated and unmyelinated s...

Past studies have found poorer performance on vertical heading judgement accuracy compared to horizontal heading judgement accuracy. In everyday life, precise vertical heading judgements are used less often than horizontal heading judgements as we cannot usually control our vertical direction. However, pilots judging a landing approach need to consistently discriminate vertical heading angles to land safely. This study addresses the impact of training on participants' ability to judge their touchdown point relative to a target in a virtual environment with a clearly defined ground plane and horizon. Thirty-one participants completed a touchdown point estimation task twice, using three angles of descent (3°, 6° and 9°). In between the two testing tasks, half of the participants completed a flight simulator landing training task which provided feedback on their vertical heading performance; while, the other half completed a two-dimensional puzzle game as a control. Overall, participants were more precise in their responses in the second testing compared to the first (from a SD of ± 0.91° to ± 0.67°), but only the experimental group showed improvement in accuracy (from a mean error of − 2.1° to − 0.6°). Our results suggest that with training, vertical heading judgments can be as accurate as horizontal heading judgments. This study is the first to show the effectiveness of training in vertical heading judgement in naïve individuals. The results are applicable in the field of aviation, informing possible strategies for pilot training.

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