The study of memory in higher vertebrates is one of the major problems of neurobiology. A simple and technically accessible experimental model is needed. Studies from this laboratory have demonstrated operant conditioning of the simplest stimulus-response pathway in the primate CNS, the wholly spinal two-neuron arc of the H-reflex. The H-reflex is the electrical analog of the spinal stretch reflex. Conditioned H-reflex change remains even after all supraspinal input is removed. Thus, H-reflex conditioning produces memory traces in the spinal cord, and is a powerful model for studying neuronal and synaptic substrates of primate memory. It may also furnish a new therapeutic approach to spasticity and other manifestations of abnormal reflex function. The goal of this project is to determine where in the spinal cord operantly conditioned changes occur and to define these changes physiologically and anatomically. The central hypothesis is that change occurs in the Ia afferent synapse on the alpha motoneuron and/or in the motoneuron itself. First, the triceps surae H-reflex in one leg is increased or decreased by chronic operant conditioning. Then, the animal is deeply anesthetized and acute physiologic and anatomic studies compare the conditioned and control sides of the spinal cord. Intracellular recordings from triceps surae motoneurons define their intrinsic properties and their responses to stimulation of homonymous and heteronymous Ia afferents. Horseradish peroxidase labelling of motoneurons and Ia afferents defines neuronal and synaptic morphology. Comparison of data from conditioned and control sides of the spinal cord reveals conditioning-induced changes in the motoneurons and/or in the Ia afferent connections to them. Study of non-triceps surae motoneurons delineates the distribution and specificity of these modifications. Subsequent stages of the work will focus on further physiologic and anatomic analysis of motoneurons and their Ia afferent synapses, on evaluation of changes in other spinal elements, and on exploration of the supraspinal structures and descending pathways responsible for altering the spinal cord. The project, through its current emphasis on the Ia synapse and alpha motoneuron, and its later attention to wider issues, should lead to important new understanding of memory in higher vertebrates.
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