Neurogenetic studies in Drosophila have contributed much to our understanding of the various forms of behavioral plasticity and the underlying molecular mechanisms. This project is a continuation of our long-term efforts to bridge the gap between these two levels of approach by elucidating the associated modification in neuronal function and structure and in neural circuit performance. Developmental and functional plasticity of neurons and neural circuits will be analyzed using a combination of genetic, molecular, morphological and physiological techniques on a collection of mutants with identified molecular defects. Genetic alterations of cAMP levels (dnc and rut) and PKA kinase activity (DC0, PKARI) cause learning disabilities, while naturally occurring variants in PKG activity (for) correlate with patterns of foraging behavior. We demonstrated in these second messenger pathway mutants altered neuronal firing pattern and synaptic plasticity, as well as abnormal processes underlying habituation behavior. K channels control neuronal firing properties and affect synaptic transmission. Interestingly, we found that mutations of different K channel subunits, Sh, slo, Hk and eag, affect synaptic plasticity and alter the habituation process often as extremely as dnc, rut, and for, suggesting that K channels are potential mediators of second messenger modulation underlying neuronal plasticity. Synaptic modification underlying learning relies on precise temporal correlations of the pre- and post-synaptic activities between neurons. Different terminal branches within a neuronal arbor can be separately modified depending on local synaptic activities for information processing. Using mutants defective in second messenger cascades and K channel subunits, we will dissect the mechanisms controlling terminal branch excitability and synaptic output level and timing in the larval neuromuscular junction. We will further develop behavioral and physiological paradigms to study these two categories of mutations in the adult escape reflex circuit to reveal molecular distinctions among the non-associative conditioning processes, habituation, dishabituation, and sensitization, which have not been well established. Such studies can extend our knowledge of the developmental and cellular processes underlying the precision and amplitude of neurotransmission and different forms of behavioral plasticity, and may suggest new therapeutical approaches to dysfunction in learning/memory processes.
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