Neuronal plasticity accompanying development and experience-dependent processes facilitates the establishment and refinement of the nervous system, while presenting significant challenges to the functional stability of the neural networks. The nervous system uses a variety of compensatory mechanisms to cope with perturbations. Recent studies suggested that structural plasticity serves as a major component for neuronal homeostasis. Our previous studies have demonstrated experience-dependent plasticity in the developing Drosophila larval visual circuit, in which ventral lateral neurons (LNvs), the postsynaptic targets of larval photoreceptors, exhibit robust structural plasticity of their dendritic arbors when animals are subjected to different visual experience. These observations also established a genetically tractable model system for mechanistic studies on the activity-dependent regulation of developmental plasticity. To investigate the contribution of genetic factors in the activity-dependent regulation of dendrite morphology, we performed forward genetic screens and cell type specific manipulations. A number of candidate genes, including cell adhesion molecules, cytoskeleton associated proteins and other critical components for synaptic organization were identified using these approaches. In addition, using two-photon time-lapse live imaging of LNvs in the developing larval brain, we established temporal profiles for dendrite morphogenesis, synapse formation and fast dendrite dynamics, and observed the strong influence on these processes imposed by visual experience. Our experiments showed that experience-dependent homeostatic mechanisms primarily target dynamic dendritic filopodia in tuning the maturity of dendritic arbors, which defines the capability for synaptogenesis and subsequent growth. These findings provided novel insights into the cellular and molecular mechanisms underlying homeostatic structural plasticity in the developing neural circuit.
