The development and plasticity of the neuromuscular junction in Drosophila will be studied using mutations that disrupt several aspects of neuronal function. The proposed research will test the hypothesis that neural activity, presumably by alterations in the level of second messengers, is a major factor involved in regulating synaptogenesis. Activity levels will be modified to different extents by mutations affecting ion channels and neurotransmitter release, whereas CAMP levels will be altered by using mutations that affect CAMP metabolic enzymes. We will use immunocytochemical staining of motor axon terminals to determine if changes in the levels of activity of motorneurons or changes in CAMP levels during development generate morphological changes. Ultrastructural reconstructions and macropatch recordings of single synaptic boutons will allow us to assess the structural and functional nature of these changes. We will also determine the sequence of events during larval development that lead to the final pattern of axon terminals, and if there are critical stages of development during which this morphology is amenable to change. We have already found that hyperactivity throughout development leads to morphological and physiological abnormalities at the Drosophila larval neuromuscular junction. The combination of conventional electrophysiological and anatomical techniques, and the powerful genetic and molecular tools developed in Drosophila, should allow us to gain much insight into the mechanisms underlying synaptic plasticity. Furthermore, this study may be valuable for the understanding of neuropathologies that result from abnormal states of neuronal activity.
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