To mate or to flee: neural mechanisms underlying action-selection

生活要求我们每天做出无数的决定。例如，我们经常面临冲突的情况，我们必须优先考虑一个目标。这些决定可以影响我们的日常生活，并共同影响我们的社会如何演变。此外，行为选择过程在神经系统疾病中受损，如成瘾、帕金森病和阿尔茨海默病。大脑如何评估可用的选项，并为每种情况选择最合适的行动？我们知道，从外部世界传递信息的线索必须不断评估，并与内部需求结合使用，以指导适当的行为选择。然而，导致这种内部评估的神经过程仍然未知，了解不同的神经元如何促进最佳行动选择将有助于我们进一步了解大脑如何工作，以及疾病中出现了什么问题。哺乳动物大脑的复杂性使得我们很难完全理解动作选择的神经回路。然而，我们可以利用大脑较小的生物体，它们每天也必须处理行为冲突。特别是果蝇Drosophila melanogaster为研究行为选择的神经机制提供了一个很好的机会。由于果蝇中可用的复杂工具，我们可以中断特定的基因，以及以高分辨率可视化和操纵单个神经元。有了这些工具，我们可以研究苍蝇的大脑在有冲突的选项时如何反应，以及它如何在其中做出选择。例如，一只果蝇如何在追求配偶或逃避捕食者之间做出选择？这些相互矛盾的信息在大脑中是在哪里以及如何被评估的，以驱动一个适当的行动？利用果蝇的一种新的行为分析，我们的目标是识别大脑中允许动物在求爱和逃避威胁之间选择的神经元，研究这些神经元如何相互连接，以及它们如何共同选择一个动作。通过研究大脑如何在细胞和神经回路水平上选择动作，在一个可访问的实验系统中，我们的目标是揭示潜在的行动选择，可能是共同的所有动物物种的基本机制。反过来，这些知识可以用来更好地了解我们大脑在健康和疾病中的复杂内部工作。

Life demands that we make innumerable decisions on a daily basis. For instance, we are often exposed to conflicting situations where we must prioritise one goal over another. Such decisions can affect our everyday life and, collectively, influence how our society evolves. Furthermore, action-selection processes are impaired in neurological disorders, such as addiction, Parkinson's disease, and Alzheimer's disease. How does the brain evaluate the available options and select the most appropriate action for each situation? We know that cues conveying information from the outside world must be constantly assessed and used in combination with internal needs to guide appropriate behavioural choices. However, the neural processes leading to this internal evaluation remain unknown.Understanding how different neurons contribute to optimal action-selection will help us advance our knowledge of how the brain works, and what goes wrong in disease. The complexity of the mammalian brain has made it difficult to fully understand the neural circuits of action-selection. However, we can take advantage of organisms with smaller brains that must also deal with behavioural conflicts on a daily basis. In particular, the fruit fly Drosophila melanogaster offers a great opportunity to investigate the neural mechanisms of action-selection. Thanks to sophisticated tools available in the fruit fly, we can interrupt specific genes, as well as visualise and manipulate individual neurons with great resolution. With these tools, we can study how the fly brain responds when there are conflicting options available, and how it chooses amongst them. For instance, how does a fruit fly choose between courting a mate or escaping a predator? Where and how is this conflicting information evaluated in the brain to drive an appropriate action?Using a novel behavioural assay in the fruit fly, we aim to identify neurons in the brain that allow the animal to choose between courting and escaping a threat, investigate how these neurons are connected with each other, and how they work together to select an action.By studying how the brain selects actions at a cellular and neural circuit level, in an accessible experimental system, we aim to reveal fundamental mechanisms underlying action-selection that might be common to all animal species. This knowledge, in turn, can be exploited to better understand the complex inner workings of our own brain in health and disease.