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

CRCNS 美德研究提案：嗅觉系统神经状态变化的计算和实验研究

• 批准号: 1724221
• 负责人: Christiane Linster
• 金额: $ 50万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1724221&HistoricalAwards=false
• 关键词: CRCNS; US; German; Research; Proposal

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).

所有动物之间的社会互动是哺乳动物大脑的一个非常重要的功能。有限或功能失调的社会互动可能对动物或人的生活质量，寿命和生殖成功产生很大影响-例如自闭症，人格障碍，威廉姆斯综合征，产前酒精综合征等。在社会交往中，特定的神经激素改变我们大脑中的感官知觉和认知过程，以适应和优化这些特定的任务。研究人员提出了一个这样的物质，催产素，对社会识别和记忆的影响，在小鼠中使用跨学科的方法，结合了最先进的实验和计算方法的详细调查。研究人员研究了催产素在社会交往中改变大脑计算的程度，以及催产素引起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，并干扰个体和群体的社会结构。理解在社会互动和识别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，为学员在本科和博士后水平。行为背景和需求可以调节大脑状态和神经计算通过涌入神经调节剂和激素。该方案利用已建立的模型系统研究大脑状态、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、去甲肾上腺素和血清素，在注意力、压力或饥饿等行为环境下释放，改变大脑网络的计算方式，以最好地应对这些行为情况。虽然有广泛的知识，这些物质的细胞和网络的影响，知识的背景下，这些释放仍然是模糊的，和相关的影响，神经调质与特定的行为情况是困难的。催产素对嗅觉系统的调节提供了一个独特的机会，可以直接询问神经处理如何被调节以实现更稳定的记忆，神经表征对稳定记忆的重要性，以及在这些记忆的形成和表达过程中感觉，调节和皮层区域之间的反馈相互作用如何相互作用。这个项目具体解决了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中气味表征的信噪比。 该项目还研究了嗅球和皮层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，研究人员采用了跨学科的方法，使用最先进的实验和计算技术。德国联邦教育和研究部正在资助一个配套项目。

项目成果

Experience enhances certainty about olfactory stimuli under bulbar cholinergic control

• DOI: 10.1101/lm.051854.120
• 发表时间: 2020-10-01
• 期刊: LEARNING & MEMORY
• 影响因子: 2
• 作者: Cho, Christina;Linster, Christiane
• 通讯作者: Linster, Christiane

Olfactory recognition memory in mice depends on task parameters.

小鼠的嗅觉识别记忆取决于任务参数。

• DOI: 10.1037/bne0000421
• 发表时间: 2020
• 期刊: Behavioral Neuroscience
• 影响因子: 1.9
• 作者: Buseck, Alison;McPherson, Katherine;Linster, Christiane
• 通讯作者: Linster, Christiane

Context-dependent odor learning requires the anterior olfactory nucleus.

• DOI: 10.1037/bne0000371
• 发表时间: 2020-08
• 期刊: Behavioral neuroscience
• 影响因子: 1.9
• 作者: Levinson M;Kolenda JP;Alexandrou GJ;Escanilla O;Cleland TA;Smith DM;Linster C
• 通讯作者: Linster C

A computational model of oxytocin modulation of olfactory recognition memory

• DOI: 10.1523/eneuro.0201-19.2019
• 发表时间: 2019-07-01
• 期刊: ENEURO
• 影响因子: 3.4
• 作者: Linster, Christiane;Kelsch, Wolfgang
• 通讯作者: Kelsch, Wolfgang

Phasic dopamine reinforces distinct striatal stimulus encoding in the olfactory tubercle driving dopaminergic reward prediction

• DOI: 10.1038/s41467-020-17257-7
• 发表时间: 2020-07
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Lars-Lennart Oettl;M. Scheller;Carla Filosa;Sebastian Wieland;Franziska Haag;Cathrin Loeb;D. Durstewitz-D.