Neuronal Activity-Dependent Development of the Nociceptive Circuit in Drosophila

[摘要] How nature and nurture interact to sculpt the nervous system, which underlies animal behaviors, has fascinated both scientists and the general public for generations.At the level of neural circuit assembly, the answer lies in the interplay between genetic programs and neural activity; the development of a functional nervous system is not just hard-wired by the genome, but depends on sensory experiences and neuronal activities.However, the mechanisms underlying the ;;activity-dependent development” of the nervous system are poorly understood, mostly due to the lack of a model system that is amenable to efficient gene manipulations and circuit analyses.My dissertation research aims to develop a Drosophila system that is suitable for identifying the mechanisms behind activity-dependent development of neural circuits from the molecular to the circuit and behavioral levels.I have largely achieved this through two projects.First, I discovered that the functional development of Drosophila somatosensory circuits depends on the sensory inputs during animal development.Our behavior analysis demonstrated that larval escaping behavior in response to noxious stimulation is suppressed if a larva experiences enhanced levels of noxious stimulation during development, demonstrating sensory input-induced plasticity.Using imaging-based physiological analyses(calcium and cAMP imaging techniques and optogenetic stimulation of neurons), we found that enhanced noxious stimulation during development reduces the synaptic transmission from nociceptors (i.e., sensory neurons detecting noxious stimuli) to the second-order neurons (SONs) in the pathway.Our study further revealed that this physiological change accounts for the suppressed behavioral outputs.Importantly, we showed that the enhanced noxious experience has no effect on other sensory modalities such as the mechanosensory pathway and elucidated the mechanism that underlies this sensory-pathway-specificity.Second, my work facilitated the discovery that the activity levels of nociceptors regulate their axonal projections in the central nervous system (CNS).Through advanced techniques that combine single-cell labeling and computational analysis, we found that the spatial arrangement of nociceptor axon terminals in the CNS reflects the locations of territories occupied by nociceptor dendrites on the body wall, forming a topographic map.The formation of this map depends on the levels of their activities, and manipulation of neuronal activity at single-cell level disrupts the map formation.This activity-dependent topography in Drosophila is likely established through the interactions of nociceptor presynaptic terminals with their postsynaptic SONs, similar to topography in vertebrates.This work is the first report of an activity-dependent topographic map in Drosophila, and has allowed for mechanistic analyses of the role of neuronal activity in neural circuit wiring.My dissertation research contributes to our understanding of how neural activity interacts with genetic programs to shape the nervous system.

[发布机构] University of Michigan

[效力级别] nociceptive system in Drosophila

[关键词] neuronal activity-dependent development;nociceptive system in Drosophila;neuronal activity-dependent topographic map;sensory-input-induced plasticity;Molecular;Cellular and Developmental Biology;Neurosciences;Science (General);Health Sciences;Science;Cell and Developmental Biology