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Activity-dependent Remodeling of Drosophila Olfactory Sensory Neurons During an Early-life Critical Period

dc.contributor.advisorMiller, David
dc.contributor.advisorBroadie, Kendal
dc.creatorGolovin, Randall Michael 2021
dc.description.abstractCritical periods are developmental windows during which neural circuits restructure to the new sensory environment. The Drosophila antennal lobe (AL) provides a genetically-tractable model system to study the cellular and molecular underpinnings of critical periods in a well-defined neural circuit. The first few days of life mark a critical period for the development of the AL. Exposing Drosophila to an ethyl butyrate (EB) odorant during this time remodels the olfactory sensory neurons (OSNs) by altering the axonal innervation pattern to their target glomerulus. Or42a-expressing OSNs show a profound loss of innervation when exposed to EB during the critical period. This remodeling results in the loss of presynaptic active zones and depends on the odorant-driven activation of Or42a OSNs. Unlike other OSNs, Or42a neuron remodeling is specific to the presynaptic axons and does not require synaptic output. Likewise, the molecular mechanisms are different as well with Or42a OSN class-specific Fragile X Mental Retardation Protein (FMRP) RNAi impairs innervation remodeling within AL synaptic glomeruli, whereas global Drosophila fragile x mental retardation 1 (dfmr1) null mutants display relatively normal odorant-driven refinement. This unique role for FMRP depends on the input of local interneurons (LNs) downstream of widespread OSN activation. Optogenetic activation of Or42a OSNs bypasses the other OSN channels and renders remodeling impervious to Or42a-targeted FMRP knockdown. The control of OSN synaptic remodeling by FMRP, with neuron-specific circuit functions, indicates how neural circuitry can compensate for global FMRP loss to reinstate normal critical period brain circuit remodeling.
dc.subjectCritical periods
dc.subjectFragile X Mental Retardation Protein
dc.titleActivity-dependent Remodeling of Drosophila Olfactory Sensory Neurons During an Early-life Critical Period
dc.type.materialtext University Graduate School

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