Paviovian Conditioning of Injured Spinal Cord Systems

描述（由申请人提供）：孤立的脊髓天生具有学习巴甫洛夫关系和工具关系的能力。然而，人们对这两种学习方式的相互作用知之甚少。目前的研究旨在进一步了解脊髓学习，并将我们对脊髓学习的经验认识提升到临床水平。先前的研究表明，不可控的电刺激会破坏脊髓的可塑性，造成长达48小时的器质性学习障碍。不可控的刺激也会破坏脊髓挫伤后的功能恢复。本提案的目的是检查脊髓机制，使和保护脊髓内的可塑性。初步结果表明，“可预测性”可以保护孤立脊髓的可塑性。用可预测（巴甫洛夫）电击治疗的大鼠随后能够学习工具关系，而不可预测的电击导致学习缺陷。我们提出的实验进一步研究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。在对胫骨前肌（US）施加更强的电击之前，对尾巴（CS）施加弱电击，将建立巴甫洛夫关系。大鼠将在不可控电击之前或之后接受巴甫洛夫条件反射治疗，并使用工具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。初步研究表明，CS可以产生？-阿片类药物介导的抗感觉，和？激动剂能够破坏由不可控电击引起的工具性学习缺陷的诱导。拟议的研究将检查CS对可塑性的保护作用是否也取决于作用于？受体。一个吗?拮抗剂（不是BNI）将与CS同时施用，以确定这是否会破坏保护作用。最后，使用各种运动和感觉测试，我们将检查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，以及它是如何被恢复的，对于发展促进脊髓损伤后恢复的新手术是至关重要的。

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.