This project by Dr. Walters will compare cellular mechanisms within the same neurons contributing to 3 classes of long-lasting alteration. These alterations, which have generally been considered separately in different biological preparations by different laboratories are: 1) adaptive responses following injury of a neuron's axon, 2) hyperexcitability of nociceptive neurons (functionally equivalent to neurons in mammalian pain pathways) during persistent nociceptive sensitization ("hyperalgesia"), and 3) aversive learning and memory. Dr. Walters will be using electrophysiological, pharmacological, and morphological methods, to characterize functionally identified neurons in an invertebrate preparation to address the following questions: First, does axonal injury induce long-term changes in excitability, synaptic transmission, and morphology in functionally diverse neurons? Second, how do alterations induced by axonal injury compare to activity-dependent alterations that have previously been linked to learning and memory. In addition, how do injury-related and learning-related effects interact? Third, is long-term plasticity induced by axonal injury initially triggered by the interruption of retrograde axonal transport of trophic factors, or do the axonal triggers involve elevation within the axon of known signals for neuronal plasticity such as the second messengers calcium and cAMP? Fourth, do cAMP and calcium in or near the cell body of the neuron contribute to the triggering of long-term plasticity during both learning and cellular reactions to axonal injury? These investigations may reveal basic mechanisms of plasticity that appeared early in evolution and which may be involved in memory, regeneration, and chronic pain-like states.***//
