Integration of olfactory and visual stimuli for navigation in Drosophila

项目摘要/摘要 动物对外部环境的变化做出反应，并促进支持生存的行为输出。班次在 动物的内部状态，或通过神经调节调节的神经元处理转变，驱动这些适应性 行为反应，影响感觉和记忆处理。依赖于状态的调制可能是有害的 当它与滥用药物，特别是酒精有关时。这个项目的目的是了解这些机制和 调节酒精记忆电路的状态依赖调制的电路基元。了解这些电路 机制将强调由压力、情绪和生理状态带来的内部状态如何影响 药物滥用障碍、渴求和复发。简而言之，果蝇黑腹果蝇被限制在一个间隔- 训练范式将气味线索与醉人剂量的酒精联系起来，并对偏好进行测试 第二天。八胺能神经元，无脊椎动物的相当于去甲肾上腺素的神经元，被发现调制 果蝇获得和提取酒精记忆所必需的嗅觉奖赏记忆回路。 对章鱼胺能神经元的生热抑制表明，只有当苍蝇处于 缺乏食物的状态，这种神经调节对于酒精的获取和恢复是必要的 记忆。体内钙成像将用于评估章鱼胺神经元亚群的活性 调节这种状态依赖的调制(饱足状态与食物匮乏状态)及其下游后- 突触伙伴。将评估已识别的状态依赖的八胺能回路的神经元活动 在醉酒期间，天真的气味暴露，气味-酒精配对，以及配对或不配对的气味重新提示。这些 实验将强调记忆处理的状态依赖机制，通过这种机制，内部状态会发生变化 会影响与滥用药物有关的记忆的获得和提取。申请者将接受培训 在钙成像和复杂的数据分析方法中跟进这些实验， 持续的职业发展培训，帮助申请者为下一阶段的职业生涯发展提供帮助 博士后研究员。申请者将继续追求依赖国家的调制机制和 这将如何影响多感官整合，从而驱动行为选择。在博士后阶段，申请者 将精通钙成像技术、计算技能和分析方面的持续培训 方法对大规模的钙离子成像数据集进行检验。此外，申请者将继续他们的 专业发展，并成长为一家学术机构的独立研究员。

PROJECT SUMMARY/ABSTRACT Animals respond to changes in their external environment and promote pro-survival behavioral output. Shifts in an animal’s internal state, or a shift neuronal processing mediated through neuromodulation, drive these adaptive behavioral responses, affecting sensory and memory processing. State-dependent modulation can be harmful when it is related to drugs of abuse, particularly alcohol. This project aims to understand the mechanisms and circuit motifs that mediate state-dependent modulation of alcohol memory circuits. Understanding these circuit mechanisms will highlight how internal state, brought about by stress, mood, and physiological state, can affect drug abuse disorders, cravings, and relapse. Briefly, Drosophila melanogaster were conditioned with a spaced- training paradigm to associate an odor cue with an intoxicating dose of alcohol, and preference was tested the following day. Octopaminergic neurons, the invertebrate equivalent norepinephrine, were found to modulate olfactory reward memory circuits necessary for alcohol memory acquisition and retrieval in fruit flies. Thermogenetic inhibition of octopaminergic neurons showed that modulation occurred only when flies were in a food-deprived state, and this neuromodulation was necessary for the acquisition and retrieval of the alcohol memory. In-vivo calcium imaging will be used to assess the activity of the subset of octopamine neurons mediating this state-dependent modulation (satiated versus food-deprived states) and their downstream post- synaptic partners. Neuronal activity of the identified state-dependent octopaminergic circuit will be assessed during intoxication, naïve odor exposure, odor-alcohol pairings, and paired- or unpaired-odor re-cue. These experiments will highlight state-dependent mechanisms for memory processing, by which shifts in internal state can affect the acquisition and retrieval of memories related to drugs of abuse. The applicant will acquire training in calcium imaging and sophisticated data-analysis methods to follow-through on these experiments, with ongoing professional development training to help develop the applicant for the next stage of their career as a postdoctoral researcher. The applicant will continue to pursue mechanisms of state-dependent modulation and how that affects multi-sensory integration, to drive behavioral choices. In the postdoctoral phase, the applicant will gain proficiency in calcium imaging techniques, computational skills, and continued training in analytical methods to examine large-scale calcium imaging data sets. Additionally, the applicant will further their professional development and grow towards becoming an independent researcher at an academic institution.