Collaborative Research: Genetic Architecture of Exploration in Drosophila

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。嗜新症是对新刺激的吸引，它在物种内和物种之间差异很大。更高水平的嗜新症被认为会导致更大的行为灵活性，影响动物适应环境变化和成功入侵新生态系统的能力。这项拟议的工作将侧重于识别导致新嗜血症的基因和神经元。这项工作将使用新的竞技场探索分析与各种和集成的遗传方法。在黑腹果蝇中，突变和转基因品系将被用来确定大脑中启动嗜新性探索所需的多巴胺信号。一个由果蝇姐妹物种产生的新的遗传图谱群体也将被用来定位这两个密切相关物种之间发现的探索行为差异所涉及的遗传变异。这两种方法将有助于解释为什么在嗜新性探索中发现昆虫物种之间存在巨大差异。这一认识可能会超越昆虫，并为其他物种的嗜新症提供线索。这项工作将进一步产生几个持久的社会效益，包括产生一个新的图谱群体，可以用来识别控制许多复杂生理和行为反应的重要遗传变异。这些血统将广泛分布给调查人员。拟议中的实验对本科生研究人员来说非常方便，将用于培训密西西比大学和休斯顿市中心大学的学生，他们中的许多人来自服务不足的群体，他们的科学探究以及神经科学和行为的遗传学方法。了解嗜新症的分子和神经基础是解释这一行为特征的广泛的种间和种内差异所必需的。这项提议的目标是了解果蝇神经系统中的嗜新症是如何编码的，包括识别负责识别新刺激并在动物中诱导唤醒的分子和神经回路。我们的中心假设是，在果蝇物种食物专门化的进化过程中，选择了减少新嗜性的遗传变异，导致失去了特定的探索；多巴胺信号也可能参与其中。对果蝇物种的新的野外探索将结合不同的遗传方法来识别导致新奇行为差异的遗传变异。长期以来，新的露天场地一直被用来测量各种实验室物种在探索中的特征和状态依赖的变化。有趣的是，生态多面手模拟果蝇积极探索新的领域，而它的姊妹物种和生态专家果蝇则不是这样。从这些果蝇姐妹物种产生的重组近亲交配谱系群体将被用来识别导致这些物种之间发现的新嗜性进化差异的数量性状基因座。此外，将使用反向遗传/转基因方法来剖析特定的多巴胺能回路在利用黑腹果蝇进行新奇唤醒过程中的作用。在这种方法中，将识别启动探索所需的多巴胺神经回路和参与受体的功能。这些方法将提供有关新嗜血症者神经生物学的前所未有的细节。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).Neophilia is the attraction to novel stimuli, and it varies strongly within and between species. Higher levels of neophilia are believed to lead to greater behavioral flexibility, effecting an animal’s ability to adapt to changes in their environments and to invade new ecosystems successfully. The proposed work will focus on identifying genes and neurons responsible for neophilia. This work will use novel arena exploration assays with varied and integrated genetic approaches. In Drosophila melanogaster, mutant and transgenic lines will be used to determine the requirements of dopamine signaling within the brain to initiate neophilic exploration. A new genetic mapping population generated from the sister species of Drosophila will also be used to map genetic variants involved in the differences in exploratory behaviors found between these two closely related species. These two approaches will help explain why enormous differences in neophilic exploration are found in insect species. This understanding will likely transcend insects and shed light on neophilia in other species. The work will further generate several lasting societal benefits, including the generation of a novel mapping population that can be used to identify important genetic variants controlling many complex physiology and behavior responses. These lineages will be broadly distributed to investigators. The proposed experiments are highly accessible to undergraduate researchers and will be used to train students at both the University of Mississippi and the University of Houston Downtown, many from underserved groups, in scientific inquiry and in the genetic approaches to neuroscience and behavior. Understanding the molecular and neural basis for neophilia is required to explain the broad inter- and intraspecific variation in this behavioral trait. The goal of this proposal is to understand how neophilia is encoded in the Drosophila nervous system, including an identification of the molecules and neural circuits responsible for recognizing novel stimuli and inducing arousal in the animal. Our central hypothesis is that during the evolution of food specialization in Drosophila species, genetic variants that reduced neophilia were selected for, resulting in a loss of specific exploration; dopamine signaling is also likely involved. Novel open field exploration of Drosophila species combined with varied genetic approaches will be used to identify the genetic variants responsible for differences in novelty-seeking behavior. Novel open field arenas have long been used to measure trait and state-dependent changes in exploration in various laboratory species. Interestingly, Drosophila simulans, an ecological generalist, actively explores novel arenas, while its sister species and ecological specialist, Drosophila sechellia, does not. A population of recombinant inbred lineages generated from these Drosophila sister species will be used to identify the quantitative trait loci responsible for the evolved differences in neophilia found between these species. Moreover, a reverse genetic/transgenic approach will be used to dissect the role of specific dopaminergic circuits in novelty arousal using Drosophila melanogaster. In this approach, the function of dopamine neural circuits and participating receptors required for the initiation of exploration will be identified. These approaches will provide unprecedented detail on the neurobiology of neophilia.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.