Paviovian Conditioning of Injured Spinal Cord Systems

描述(申请人提供)：分离的脊髓具有学习巴甫洛夫关系和器质性关系的能力。然而，人们对这两种学习方式的相互作用知之甚少。目前的研究旨在加深对脊髓学习的了解，并将我们对脊髓学习的经验理解提升到临床水平。先前的研究表明，不可控的电刺激会破坏脊髓的可塑性，导致长达48小时的工具性学习缺陷。无法控制的刺激也会破坏脊柱挫伤后功能的恢复。这项建议的目的是检查脊髓机制，使脊髓内的可塑性，并保护。初步结果表明，“可预见性”可以保护分离的脐带的可塑性。接受可预测(巴甫洛夫)休克治疗的大鼠随后能够学习一种工具性关系，而不可预测的休克会导致学习缺陷。我们提出的实验进一步检验了可预测性和可塑性之间的相互作用。首先，我们将研究在脊髓神经元中建立巴甫洛夫关系是否可以免疫或逆转不可控电刺激的有害影响。巴甫洛夫关系将通过在对胫骨前肌(US)施加更强的电击之前立即对尾部(CS)施加弱电击来建立。在无法控制的休克之前或之后，大鼠将接受巴甫洛夫条件反射治疗，并将使用工具性任务评估它们的学习能力。然后，我们将研究调节可塑性的神经生物学级联反应。初步研究表明，CS可产生？-阿片介导的抗伤害性感觉。激动剂能够破坏由于无法控制的休克而产生的工具性学习缺陷的诱导。拟议的研究将检验CS对可塑性的保护作用是否也依赖于作用于？受体。A？拮抗剂(Nor BNI，I.T.)将与CS同时给药，以确定这是否会破坏保护作用。最后，使用各种运动和感觉分析，我们将检验巴甫洛夫条件反射对挫伤后功能恢复的影响。了解脊髓的可塑性，它是如何被破坏的，以及如何恢复它，对于开发促进脊髓损伤后恢复的新程序是至关重要的。

DESCRIPTION (provided by applicant): The isolated spinal cord is inherently capable of learning about Pavlovian and instrumental relationships. Little is known, however, about the ways in which these two forms of learning may interact. The current studies aim to further knowledge of spinal learning, and also to take our empirical understanding of learning n the cord to a clinical level. Previous studies have shown that uncontrollable electrical stimulation undermines the plasticity of the cord producing an instrumental learning deficit that lasts for up to 48 hrs. Uncontrollable stimulation also undermines the recovery of function after a spinal contusion injury. The aim of this proposal is to examine spinal cord mechanisms that enable, and protect plasticity within the spinal cord. Preliminary results suggest that 'predictability' can protect plasticity in the isolated cord. Rats treated with predictable (Pavlovian) shock are subsequently able to learn an instrumental relationship, whereas unpredictable shock results in the learning deficit. The experiments we propose further examine the interactions between predictability and plasticity. First, we will examine whether establishing a Pavlovian relationship in spinal neurons can immunize or reverse the detrimental effects of uncontrollable electrical stimulation. A Pavlovian relationship will be established by applying a weak shock to the tail (CS) immediately before a stronger shock to the tibialis anterior muscle (US). Rats will be treated with Pavlovian conditioning before or after uncontrollable shock and their capacity to learn will be assessed using an instrumental task. We will then examine neurobiological cascades that modulate plasticity. Preliminary studies suggest that a CS can produce a ?-opioid mediated antinociception, and ? agonists are able to undermine the induction of the instrumental learning deficit produced with uncontrollable shock. The proposed studies will examine whether the protective effects of the CS on plasticity also depend on a ligand that acts on the ? receptor. A ? antagonist (nor BNI, i.t.) will be administered concurrently with the CS to determine whether this undermines the protective effects. Finally, using a variety of motor and sensory assays, we will examine the implications of Pavlovian conditioning for the recovery of function after a contusion injury. An understanding of spinal cord plasticity, how it is disrupted, and how it can be restored, is essential to the development of new procedures that promote recovery after a spinal injury.