Effects Of Chronic Stress On The Neuronal Activity Of Learning And Memory Related Neural Circuits In Drosophila

All organisms live in a dynamic environment,and stress response is crucial for survival.In order to cope with changes in the internal and external environment,animals will develop a series of adaptive behaviors.The neuromolecular mechanism behind these behaviors have always been the focus of scientists.Using chronic stress as a stressor to study the molecular mechanisms behind mood disorders has been greatly developed.In this paper,we use Drosophila as a model animal to study the effects of chronic stress on the activity of olfactory memory-related neurons at the cellular level and then to analyze the relevant neural circuits.In our previous work,we have established a model of chronic stress(repeated mechanical shock)and found that Drosophila will enter a state of depression-like behavior after chronic stress treatment,showing behavior despair,impaired learning ability,anhedonia,decreased sexual desire and other depression-like behaviors.This paper mainly studies the impairment of cognitive function in Drosophila.In order to understand the process and mechanism of complex neural networks to control animal behavior,it is necessary to detect and record neural activities at the cellular level,so as to analyze the neural circuits regulated.The research work in this paper includes the following two aspects:1.Chronic stress affects the activity of dopamine downstream neuronsIn this paper,two activity detection tools(ANF-GFP and CaLexA)were used to find that chronic stress did not significantly affect the activity of dopaminergic neurons in drosophila,but had a greater effect on the activity of mushroom body KCs and mushroom body output neurons.Chronic stress causes MBON-γ1pedc>α/β to be activated,while MBON-γ1pedc>α/β is required for the acquisition and extraction of aversive olfactory memory.In KCs neurons,after the chronic stress treatment of Drosophila,α′/β′ neuronal activity was inhibited and γ neurons were activated.The α’/β’ neurons are essential for the solidification of olfactory learning and memory,while γ are necessary for the maintenance of short-term memory.2.Synaptic connection analysis between NPF neurons and dopamine neuronsThe results suggest that chronic stress may lead to decreased NPF promoter activity in P2 cells of NPF neurons,thereby reducing NPF expression level.However,there was no detectable change in NPF neuron activity.I also used trans-Tango,GRASP,and a series of synaptic labeling experiments to find potential upstream neurons that directly regulate dopamine neurons.My analysi s failed to find evidence that NPF and DA neurons formed synapses.The results of syb-GRASP analysis suggest that 5-ht neurons may play a role upstream of DA neurons.