CRCNS US-German Research Proposal: Computational and experimental investigation of neural state changes in the olfactory system

所有动物之间的社会互动是哺乳动物大脑的一项非常重要的功能。有限或功能不良的社交互动会对动物或人的生活质量、寿命和繁殖成功产生很大影响--例如自闭症、人格障碍、威廉姆斯综合症、产前酒精综合症等。在社会互动中，特定的神经激素改变了我们大脑中的感觉感知和认知过程，以适应和优化这些特定的任务。研究人员建议使用一种结合了最先进的实验和计算方法的跨学科方法，在小鼠身上详细研究催产素对社会识别和记忆的影响。研究人员研究了催产素在多大程度上改变了社交互动过程中大脑的计算，以及催产素导致这些变化的神经机制。例如，缺乏催产素会限制动物的社会识别能力和记忆，并干扰个人和群体的社会结构。了解在社会互动和认知中发挥作用的系统，对理解和治疗社会互动障碍具有潜在的高度影响。该项目还为本科生和博士后水平的受训者提供跨学科(计算和神经生物学)和国际(美国和德国)的研究机会。行为背景和需求可以通过神经调节剂和激素的流入来调节大脑状态和神经计算。这项建议利用一个成熟的模型系统来研究大脑状态、神经计算和可塑性之间的关系。神经激素催产素在特定的行为情况下被触发，并在这些情况下支持神经可塑性和学习。其他神经调节剂，如乙酰胆碱、去甲肾上腺素和5-羟色胺，在注意力、压力或饥饿等行为背景下释放，改变大脑网络的计算方式，以最好地对这些行为情景做出反应。尽管对这些物质的细胞和网络影响有广泛的了解，但关于这些物质释放的背景知识仍然含糊不清，而且很难将神经调节剂的影响与特定的行为情况联系起来。催产素对嗅觉系统的调节提供了一个独特的机会，直接询问神经处理是如何调制的以实现更稳定的记忆，神经表征对稳定的记忆是如何重要的，以及在这些记忆的形成和表达过程中感觉、调制和皮质区域之间的反馈相互作用是如何相互作用的。本项目专门研究催产素如何以及通过哪些(A)网络和(B)细胞和突触机制改变嗅球气味表征的信噪比。该项目还研究了嗅球和皮质之间的反馈回路如何增强稳定的气味轨迹。为了实现这些目标，研究人员应用了一种跨学科的方法，使用最先进的实验和计算技术。德国联邦教育和研究部(BMBF)正在资助一个配套项目。

Social interactions between all animals are a highly important function of mammalian brains. Limited or mal-functioning social interactions can have a high impact on an animal or person's life quality, life span, and reproductive success - examples include Autism, Personality disorders, Williams syndrome, Prenatal alcohol syndrome and others. During social interactions, specific neuro-hormones change sensory perception and cognitive processes in our brains to be adaptive and optimized to these specific tasks. The investigators propose a detailed investigation of the effects of one such substance, oxytocin, on social recognition and memory using an interdisciplinary approach in mice that combines state of the art experimental and computational approaches. The investigators study to what extend oxytocin changes computations in the brain during social interactions, the neural mechanisms through which oxytocin causes these changes. For example, a lack of oxytocin can limit an animal's social recognition capacity and memory and interfere with social structures in individuals and groups. Understanding systems that play a role in social interactions and recognition has a potential high impact on understanding and treating disorders of social interactions. The project also offers interdisciplinary (computational and neuro-biology) and international (USA and Germany) research opportunities for trainees at the undergraduate and postdoctoral level.Behavioral context and demands can modulate brain state and neural computations via influx of neuromodulators and -hormones. This proposal studies the relationships between brain state, neural computation, and plasticity by taking advantage of a well-established model system. The neurohormone oxytocin is triggered during specific behavioral situations and supports neural plasticity and learning in those situations. Other neuromodulators, such as acetylcholine, noradrenaline, and serotonin released in response to behavioral contexts such as attention, stress, or hunger change how brain networks compute to best respond to these behavioral situations. Although there is extensive knowledge of cellular and network effects of these substances, knowledge about contexts in which these are released remains vague, and correlating the effects of neuromodulators with specific behavioral situations is difficult. Olfactory system modulation by oxytocin provides with a unique opportunity to directly ask how neural processing is modulated to enable more stable memories, what about neural representations is important for stable memories, and how feedback interactions between sensory, modulatory, and cortical areas interact during the formation and expression of these memories. This project specifically addresses how and through which (a) network and (b) cellular and synaptic mechanisms oxytocin changes the signal-to-noise ratio of odor representations in the olfactory bulb. The project also examines how the feedback loop between olfactory bulb and cortex enhances stable odor trajectories. To achieve these objectives, the investigators apply an interdisciplinary approach using state of the art experimental and computational techniques. A companion project is being funded by the Federal Ministry of Education and Research, Germany (BMBF).