Genetics of social space in Drosophila melanogaster

社会互动对个体的正常发展和健康至关重要，但社会行为的遗传和神经基础仍然知之甚少。***我感兴趣的是确定动物对另一个相似个体的存在做出反应的机制，从感知到整合和决策：动物如何决定如何处理附近另一个个体的信息？社会互动的潜在机制是什么？***我用果蝇对这个问题做出了重大贡献。我开发了强大的行为分析——社会空间和对压力个体的回避——允许对社会互动进行强大的量化，并确定潜在的神经回路。此外，通过操纵水疱单胺转运体，我以前的工作表明多巴胺在调节各种行为（包括个体间隔）中的作用。***在接下来的五年里，我建议把重点放在多巴胺在社会行为中的作用上。我们将在黑腹果蝇中使用遗传和生化工具，以回答以下问题：多巴胺的水平是否与个体距离直接相关？哪些多巴胺受体影响社会行为？哪些神经元亚群表达多巴胺和多巴胺受体参与社会行为？它们调节的下游神经通路是什么？在研究生和本科生的帮助下，我们将使用基因突变和药理学方法来解决这些问题；我们将识别负责个体空间决定的神经元回路，通过屏幕阻断和增强突触传递，使用特定的驱动器。***这项工作将开始绘制对附近另一只苍蝇的基本（非性和非攻击性）反应的中枢脑神经基质。这项工作不仅与果蝇行为的研究有关，而且与其他生物社会行为的遗传学有关。事实上，对于最初在果蝇身上解剖的其他行为——学习和记忆、昼夜节律——社会行为的细胞和分子基础可能会通过进化而被保存下来，以分子“工具箱”的形式从前社会物种进化到后社会物种。由于我开发的分析方法很容易掌握，从事这个新研究项目的学生将迅速成为生物化学、神经学和遗传技能方面的专家，这些技能在学术界、政府和工业研究中都是非常可取的。学生将能够以有意义的方式为科学知识做出贡献，并将有一个平台来发展他们在研究或其他技术领域的职业兴趣。我计划培养大约5名硕士，2名博士和15名本科生。*********

Social interactions are crucial to the proper development and health of individuals, but the genetic and neural bases of social behavior are still poorly understood.***I am interested in determining the mechanisms by which animals respond to the presence of another similar individual, from perception to integration and decision making: how does an animal decide what to do with the information that an other individual is nearby? What are the mechanisms underlying social interactions?***I have made significant contributions to this question, using Drosophila melanogaster. I developed powerful behavioural assays - social space and avoidance of stressed individuals - allowing for powerful quantification of social interactions, and determination of the underlying neural circuits. In addition, through the manipulation of the vesicular monoamine transporter, my previous work suggests a role for dopamine in the modulation of various behaviours, including individual spacing.***Over the next five years, I propose to focus on the involvement of dopamine in social behaviour. We will use genetic and biochemical tools in Drosophila melanogaster, in order to answer the following questions: Does the level of dopamine directly correlate with individual distance? Which dopamine receptors are influencing social behaviour? Which subpopulation of neurons expressing dopamine and dopamine receptors are involved in social behaviour and what are the downstream neural pathways that they modulate? With the help of graduate and undergraduate students, we will address these questions using both genetic mutants and pharmacological approaches; and we will identify the neuronal circuitry responsible for individual space determination, through a screen blocking and enhancing synaptic transmission, using specific drivers.***This work will initiate the mapping of the central brain neural substrate underlying basic (non-sexual and non-aggressive) response to another nearby fly. This work will be relevant not only to studies of Drosophila behaviour, but also to genetics of social behaviour in other organisms. Indeed, as for other behaviours initially dissected in Drosophila - learning and memory, circadian rhythm - the cellular and molecular basis of social behaviour might be conserved through evolution, through pre-social to eu-social species in the form of a molecular "tool kit".***As the assays that I developed are easy to master, the students working on this new research program will become experts rapidly in biochemical, neurological, and genetic skills that are highly desirable in academia, government and industry research. The students will be able to contribute in a meaningful way to scientific knowledge, and will have a platform to develop their interests in pursuing a career in research or other technical fields. I plan on training approximately five MSc, two PhD and fifteen undergraduate students.*********