A Drosophila Melanogaster Model For The Interruptive Effect Of Pain And The Underlying Neural Circuit Mechanisms

Animals need to adjust their behavior in a timely manner in the changing environment to seek advantage and avoid harm.Correspondingly,the brain treats a variety of complex environmental stimuli differently,and signals related to survival and reproduction are often prioritized.Pain is a subjective perception of nociceptive sensations,meaning that substantial or potential physical impairment has occurred,so pain-related signals are generally prioritized.In terms of behavioral performance,when an animal is subjected to a nociceptive stimulus,it is often aborted from the task it is currently engaged in in order to better cope with the nociceptive stimulus and alleviate pain.This phenomenon is known as the interrupting effect of pain.Clinically,the pain disruption effect can well explain the interference effect of various kinds of pain,especially chronic pain,on the patient’s normal work and life.Understanding the neurobiological mechanisms of the disruption effect of pain is of great significance for both pain coping strategies and the development of analgesic drugs.It is generally believed that the interruption effect reflects the strong attraction effect of pain on attention,that is,attention bias is the underlying mechanism of the pain interruption effect.However,to date,neurobiological studies related to the disruption effect are still lacking,and specific neural and molecular mechanisms have not been elucidated.In this paper,we observe the effect of nociception on the odor behavior of fruit flies by electric shock and heat shock,and prove that the interruption effect of pain is conserved in Drosophila melanogaster,an invertebrate genetic model animal;The mechanism of its neural circuits is further explored.The work of this thesis mainly includes the following aspects:1.Established a behavioral paradigm that can be used to study the interrupting effects of Drosophila pain: blocking odor response by electric shock(BOBE).Using this paradigm,this paper shows that nociceptive electrical stimulation has a significant inhibitory effect on odor response,and its inhibition effect is positively correlated with voltage intensity.This inhibitory effect is odor-specific,and electric shocks exhibit similar inhibitory effects on disgusting odors and reward odors.In addition,whether it is a congenital avoidance behavior of disgusting odors or an acquired odor avoidance response,electric shocks show a similar degree of inhibition.The results of these behavioral analyses suggest that nociceptive electric shocks affect the significance of odor rather than potency.In addition to electrical stimulation,this study also found that nociceptive heat stimulation is also able to block odor response by heat(BOBH),and more importantly,this blocking effect requires a gene that feels heat pain,painless.In conclusion,the above experimental evidence proves that in invertebrate Drosophila melanogaster,nociceptive stimuli can also interrupt the animal’s normal behavioral response to odors,suggesting that the interrupting effect of pain has some evolutionary conservatism.It can be seen that studying the neural mechanisms of BOBE is expected to deepen our understanding of the interrupting effect of pain.2.It was found that the interrupting effect of nociceptive electrical stimulation can be regulated by the higher nerve centers of the Drosophila brain,further demonstrating the evolutionary conservatism of the pain disruption effect.The mushroom body is one of the most studied higher nerve centers in the adult fly brain,and its function is closely related to cognitive abilities such as learning memory and attention.This paper found that neurotransmitter release from mushroom body neurons is necessary for BOBE.Interestingly,in the three major classes of Kenyon cells that make up neurons in mushrooms,α/β and γ neurons are necessary for BOBE,while α′/β′ neurons are not important for BOBE.Since the function of α′/β′ neurons is necessary for both olfactory memory acquisition and curing,this shows that BOBE is very different from the underlying neural mechanism of olfactory memory,suggesting that there are specific neural circuits in the mushroom neural network that regulate BOBE.3.Fine analysis of the microcircuit of the BOBE mushroom body nerve.In addition to Kenyon cells,dopamine neurons(DAN)and mushroom body output neurons(MBON)are also projected onto the mushroom body lobes.Its projection areas overlap each other,forming 15 compartments on the leaflets of the mushroom body.These chambers are considered functional units of the mushroom body.This paper found that synaptic release from PPL1-α3,PPL1-γ1pedc and MBON-γ1pedc>α/β mushroom output neurons are necessary for BOBE by screening the highly specific mushroom body Split-Gal4 strains.This suggests that there are two local microcircuits that regulate BOBE in the mushroom neural network:PPL1-γ1pedc and MBON-γ1pedc>α/β projected to the γ1pedc chamber,and PPL1-α3projected to the α3 chamber.How these two neural pathways coordinate to regulate BOBE needs to be further studied.