Plasticity of sensorimotor behaviour

我研究项目的长期目标是了解脊椎动物行为可塑性的神经学基础。我的研究计划的短期目标是确定对脊髓的感觉和棘上输入的操纵如何改变大鼠运动肢体功能和完整脊髓通路的强度。脊柱可塑性，以脑干-脊柱连接加强的形式，是单侧脊柱横断（半切）后颈部（颈椎）区域呼吸运动恢复的基础。这种强化通过去除脊髓的感觉输入（脊髓感觉去神经支配，SSD）而增强。SSD对呼吸以外行为的影响尚未被量化，尽管这将为了解脊髓回路的可塑性能力提供有价值的见解。我的实验室非常适合解决这个问题，因为我们可以定量地评估老鼠的感觉运动能力，包括运动能力。特别是，我们测量了地面反作用力（GRF），这是一种评估大鼠地上运动的新颖而敏感的方法。我们建议研究半切后SSD是否会改变运动肢体功能，以及这是否伴随着运动脑干-脊髓连接强度的改变。具体来说，AIM 1验证了SSD改善颈椎半切术后前肢运动功能的假设。我们将使用GRF和运动学分析来测量两组半切大鼠在两种不同运动任务中的前肢功能。AIM 2通过将上述方法应用于胸脊髓并测量后肢功能，验证了SSD的影响可推广到脊髓其他区域的假设。最后，AIM 3验证了脊髓半切后，SSD增加脑干与肢体运动神经元连接强度的假设。这将通过记录有和没有SSD的半切大鼠脑干通路刺激引起的前肢和后肢运动神经的电信号振幅来完成。这些实验将为整个脊髓的神经回路的潜力提供重要信息，以促进运动行为的改变。

The long term objective of my research program is to understand the neurological basis for behavioural plasticity in vertebrates. The short term objective of my research program is to determine how manipulation of sensory and supraspinal inputs to the spinal cord alter locomotor limb function and the strength of intact spinal pathways in rats. Spinal plasticity, in the form of strengthening of brainstem-spinal connections, underlies the recovery of breathing movements after unilateral spinal transection (hemisection) in the neck (cervical) region. This strengthening is enhanced by removal of sensory input to the spinal cord (spinal sensory denervation, SSD). The effects of SSD on behaviour other than breathing have not been quantified, although this would provide valuable insight into the plastic capabilities of spinal circuitry. My laboratory is well suited to address this problem because we can quantitatively assess sensorimotor, including locomotor, abilities in rats. In particular, we measure ground reaction forces (GRF), a novel and sensitive method for assessing overground locomotion in rats. We propose to investigate whether SSD alters locomotor limb function after hemisection and whether this is accompanied by altered strength in locomotor brainstem-spinal connections. Specifically, AIM 1 tests the hypothesis that SSD improves forelimb locomotor function after cervical hemisection. We will measure forelimb function using GRF and kinematic analysis during 2 different locomotor tasks in groups of hemisected rats with and without SSD. AIM 2 tests the hypothesis that the effect of SSD is generalizable to other regions of the spinal cord, by applying the above approach to the thoracic spinal cord and measuring hindlimb function. Finally, AIM 3 tests the hypothesis that SSD increases the strength of brainstem connections to limb motoneurons after spinal hemisection. This will be accomplished by recording the amplitude of electrical signals in fore- and hindlimb motor nerves evoked by stimulation of brainstem pathways in hemisected rats with and without SSD. These experiments will provide important information regarding the potential of neural circuitry throughout the spinal cord to facilitate changes in motor behaviour.