Principles of Decision-making Neurons Switching between Alternative Behaviours

我的研究项目的长期目标是了解果蝇（Drosophila melanogaster）大脑中的神经元群如何调节替代行为。理论计算表明，少量这样的“决策”神经元可以控制两种行为之间的二进制切换。为了识别决策神经元，我建立了雄性交配决策的两种行为范式。较长的交配持续时间（LMD）发生在雄性在持续接触竞争对手后延长交配时间，而较短的交配持续时间（SMD）发生在雄性性满足时。这种简单的行为度量是可重复的，可量化的，并且很容易适应基因操作，使其成为研究决策神经元的强大模型系统。虽然LMD和SMD都涉及独特的感觉模式，但它们对特定的中间神经元和记忆回路有共同的要求，这表明相同的决策神经元调节两种行为之间的相互作用。为了确定控制LMD或SMD决定的神经元，我们筛选了果蝇中已知的神经肽信号通路，并确定了四个表达SIFa神经肽的神经元，已知SIFa神经肽与这两种行为有关。我们未来5年的目标是确定并充分表征表达sifa的神经元调节LMD和SMD的整合电路。这些研究将揭示果蝇决策神经元的基本回路原理。这项工作不仅与苍蝇行为的研究有关，而且与其他生物决策行为的遗传学有关。事实上，就像最初在果蝇身上解剖的许多其他神经机制一样——例如学习和记忆——决策行为的细胞和分子基础很可能以分子“工具包”的形式在整个进化过程中被保存下来。这一特征将帮助我们开始理解具有更复杂神经系统的生物体在细胞和分子水平上的行为的神经基础。***独特的行为模式加上对已识别神经元的研究将为学员提供神经科学，遗传学和分子生物学方面无与伦比的专业知识-所有这些都是学术，政府和私营部门研究中非常需要的技能。学生将能够为科学知识做出贡献，并将有一个坚实的平台来发展他们在研究或其他相关领域的职业兴趣。

The long-term goal of my research program is to understand how groups of neurons in the brain of the fruit fly Drosophila melanogaster can regulate alternative behaviours. Theoretical calculations suggest that small numbers of such “decision-making” neurons can control a binary switch between two behaviours. To identify decision-making neurons, I established two alternative behavioural paradigms of male's mating decision. Longer-mating-duration (LMD) occurs when males prolong mating following persistent exposure to rivals, whereas shorter-mating-duration (SMD) occurs when males are sexually satiated. This simple behavioural metric is reproducible, quantifiable, and is easily amenable to genetic manipulation, making this a powerful model system for studying decision-making neurons. While LMD and SMD each involve unique sensory modalities, they have shared requirements for specific interneurons and memory circuits, suggesting the same decision-making neurons regulate the interplay between the two behaviours. To identify neurons that control the LMD or SMD decision, we screened known neuropeptide signaling pathways in Drosophila and identified four neurons that express the SIFa neuropeptide, which is known to be associated with both behaviours. Our goal for the next 5 years is to identify and fully characterize the integrative circuits of the SIFa-expressing neurons that regulate LMD and SMD. These studies will reveal fundamental circuit principles of decision-making neurons in Drosophila. The proposed work is not only relevant to studies of fly behaviour but also to the genetics of decision-making behaviour in other organisms. Indeed, like many other neural mechanisms initially dissected in Drosophila – e.g. learning and memory – the cellular and molecular basis of decision-making behaviour is likely to be conserved throughout evolution in the form of a molecular “toolkit”. This feature will help us begin to understand the neural basis of behaviour at the cellular and molecular level in organisms with more complex nervous systems.***The unique behavioural paradigm coupled with study of identified neurons will provide trainees with unparalleled expertise in neuroscience, genetics, and molecular biology – all highly desirable skills for academic, government and private sector research. The students will be able to contribute to scientific knowledge and will have a solid platform to develop their interests in pursuing a career in research or other related fields.