Paviovian Conditioning of Injured Spinal Cord Systems

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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.