Neurogenetic basis of social space determination

社会互动对个体的正常发展和健康至关重要，但人们对社会行为的遗传和神经基础仍知之甚少。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神经遗传学机制，从感知到整合和决策：社会互动背后的基本机制是什么？我对这个问题做出了重大贡献，在醋蝇身上，通过研究发生在任何其他更复杂的社会互动之前的一种行为：到最近邻居的距离，或社会间隔。我最近的研究表明，中枢神经系统是如何决定间隔的。一种性别特有的神经回路正在成为社交间隔的调节器。它涉及到多巴胺能信号和蘑菇体。在突触水平上，我的团队将与人类神经发育障碍相关的基因(如Neurobeachin，一种锚定蛋白，一种神经连接蛋白，一种细胞黏附蛋白和一种高度保守的转录因子)牵涉到果蝇的社会间隔决定中。在接下来的五年里，我们将使用社交间隔分析结合神经操作来研究已识别的大脑结构以及新的大脑结构在社交间隔中的作用。我们将回答以下问题：蘑菇体的哪些神经元输入和输出对社会间隔是重要的？还有哪些大脑结构是重要的？除了多巴胺，还有哪些神经递质在影响社会行为？它们调节的下游神经通路是什么？是什么决定了我们观察到的性影响？在研究生和本科生的帮助下，我们将绘制出对附近另一只苍蝇做出基本(非性和非攻击性)反应的中枢神经底物图。这项工作不仅将与果蝇行为的研究相关，还将与其他生物的社会行为遗传学相关。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，通过前社会性物种和欧洲社会性物种的分子“工具包”的形式得到保守。由于我开发的分析方法很容易掌握，参与这个新研究项目的学生将很快成为生化、神经学和遗传技能方面的专家，这些技能在学术界、政府和行业研究中都是非常受欢迎的。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追求职业生涯的兴趣。我计划培养大约4名硕士、5名博士和20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 neurogenetic mechanisms by which animals respond to the presence of another similar individual, from perception to integration and decision making: What are the fundamental mechanisms underlying social interactions? I have made significant contributions to this question, in the vinegar fly Drosophila melanogaster, through the study of a behaviour that occurs prior to any other more complex social interactions: the distance to the closest neighbour, or social spacing. My recent work suggests a neural pathway for how the central nervous system is underlying the decision process of spacing. A sex specific neural circuit is emerging as a modulator of social spacing. It involves dopaminergic signalling and the mushroom bodies. At the synaptic level, my team implicated genes associated with human neurodevelopmental disorders (such as Neurobeachin, an anchor protein, Neuroligin, a cell adhesion protein and FoxP, a highly conserved transcription factor) in the social spacing decision of the flies. Over the next five years, we will use social spacing assays in combination with neural manipulations to investigate the role of identified, as well as new brain structures, in social spacing. We will answer the following questions: Which neuronal input and output to the mushroom body are important for social spacing? Which other brain structures are important? Which neurotransmitters beyond dopamine are influencing social behaviour? What are the downstream neural pathways that they modulate? What determines the sex-effect we observed? With the help of graduate and undergraduate students, we will map 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 4 MSc, 5 PhD and twenty undergraduate students.