Neural plasticity has many forms, which are expressed at distinct levels and serving specific functions. Recent studies have indicated that, beside the classic hebbian form plasticity, neurons also utilize homeostatic mechanisms to respond to changes in neuronal activity, generated during development or through experience, for the purpose of maintaining the normal functionality. As an essential adaptive mechanism for nervous system, homeostatic plasticity is conserved through evolution, being demonstrated in both vertebrates and invertebrates. However, its underlying molecular mechanism is virtually unknown. Drosophila as a model system has made valuable contributions to our general understanding of neural development and synaptic plasticity. The bi-directional homeostatic structural plasticity we discovered in fly larval visual system also provides us opportunities to perform large-scale genetic studies and to gain a comprehensive understanding on how dendrite morphology is regulated by genetic programing and neuronal activity. To this end, we have carried out genome-wide RNAi and loss-of-function mutant screens and identified a number of interesting candidates, including novel cell adhesion molecules, revealing a critical role for cellular communications in the structural plasticity. In addition, to determine the developmental and environmental cues that provide regulatory mechanisms for the wiring plasticity in fly visual circuit, we are characterizing the function of local inhibitory inputs in regulating the experience-dependent plasticity. New genetic screens in combination of calcium imaging and high resolution cell biological studies will continue to provide mechanistic insights into the homeostatic control of structural and functional synaptic plasticity. During the fiscal year, we also spent a large amount of effort to set up the equipment and protocols for our proposed research programs, including dissection scopes and stations for fly pushing, incubators for fly culture, general molecular biology reagents and tools, as well as three sets of microscopes to serve the needs of different types of imaging experiments. Our lab now routinely maintains around 800 lines of transgenic or mutant Drosophila lines, and is well equipped to carry out the advanced morphological and functional studies in fly nervous systems. These efforts will help us establish a productive research group and provide training opportunities for young scientists.

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Sheng, Chengyu; Javed, Uzma; Gibbs, Mary et al. (2018) Experience-dependent structural plasticity targets dynamic filopodia in regulating dendrite maturation and synaptogenesis. Nat Commun 9:3362
Yin, Jun; Gibbs, Mary; Long, Caixia et al. (2018) Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity. Cell Rep 25:1181-1192.e4
Yin, Jun; Yuan, Quan (2014) Structural homeostasis in the nervous system: a balancing act for wiring plasticity and stability. Front Cell Neurosci 8:439
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Klassen, Matthew P; Yuan, Quan (2013) Dendrite plasticity: branching out for greener pastures. Curr Biol 23:R687-8