Experience-dependent regulation of dendrite morphogenesis and plasticity

National Institute Of Neurological Disorders And Stroke

Investigators

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Abstract

During the past few years, our group has employed the Drosophila model to investigate structural homeostatic plasticity during dendrite development. Extensive genetic and imaging studies help us uncovered specific molecular pathways serving critical functions in this process. Importantly, our findings demonstrate that fundamental principles guiding dendrite plasticity are shared across species, and the mechanisms controlling synapse formation and maturation appear to be their core elements. In 2021, we published two studies illustrating two key molecular pathways involved in organizing and supporting cholinergic synapse formation and maturation. Specifically, neuronal lipid transport, supported by neuronal LpR receptors and glia-derived apolipoproteins, as well as the postsynaptic cholinergic signaling, mediated by Drosophila nicotinic acetylcholine receptors (nAchR), are both targeted by activity-dependent transcriptional regulations, and critical for dendrite development and synaptic functions. To expand upon these findings, we are exploring new techniques, including lipidomics and metalolomics to analyze changes in lipid profiles associated with genetic deficits, and proximity labeling to identify molecular compositions of the protein complex organized around the nAchR subunits. These newly established experimental paradigms lead us to the discovery of a previously uncharacterized class of glia-derived lipid binding proteins, as well as the establishment of preliminary maps of the postsynaptic density of central cholinergic synapses at two developmental stages. These exciting new findings will be validated and characterized by extensive genetic and imaging studies in the coming year.