The raphe - hippocampus glutamatergic pathway: role in hippocampal rhythms and function

中缝-海马谷氨酸通路：在海马节律和功能中的作用

• 批准号: RGPIN-2018-06765
• 负责人: Amilhon, Bénédicte
• 金额: $ 2.77万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761459
• 关键词: raphe; hippocampus; glutamatergic; pathway; role

Memories shape behavior; they are the building blocks that constitute our record of life experience and modulate our response to specific situations. Memory formation can be influenced in many ways, one of the strongest being emotional state. Indeed, memories formed in heavy emotional contexts leave a strong imprint in our minds. The neurobiological basis underlying this link between memory and emotion remains unclear. Two brain regions are likely to be involved: on one hand, the hippocampus (HP) is known to be essential for memory formation and is also involved in emotional behavior, notably anxiety; on the other hand, the raphe is well known for processing of emotion-related information. Raphe neurons that use the neurotransmitter glutamate and contact the HP have recently been identified. Very little is known about these glutamatergic neurons and their role in influencing memory formation or other types of HP-related behavior. The goal of this project is to provide the very first in-depth characterization of this novel brain pathway and unravel its role in memory formation and emotion. The first aim of this research project is to identify the specific localization of glutamatergic neurons projecting to the HP within the raphe, which will provide information about their expected functions. The second aim is to record the activity of HP-projecting glutamatergic neurons in freely behaving mice to unravel the behavioral periods during which they are active. Considering that the role of the HP has been demonstrated in both spatial memory and anxiety, both types of behaviors will be studied. Activity patterns will be recorded using a technique called calcium imaging, which allows to visualize neuronal activity through changes in fluorescence in a great number of neurons simultaneously. This second part of our proposal will reveal when these neurons are active in relation to specific behavioral contexts. The final aim of this research project is to manipulate the activity of this glutamatergic pathway to establish a causal relationship between glutamatergic neuron activity and behavior. This will be achieved using a technique called optogenetics, which allows to either activate neurons or silence them using light. The results generated will allow to understand if glutamatergic raphe neurons projecting to the HP are responsible for memory formation or anxiety. Understanding how neurons from different brain regions communicate together to generate behavior is currently the main challenge of neuroscience research. This project addresses this challenge using a combination of cutting-edge techniques to reveal how the raphe communicates with the HP to modulate memory formation via emotional state. Understanding this brain mechanism is therefore a crucial first step to reveal how our brain “codes for what matters”.

记忆形状的行为；它们是构成我们生活经验记录并调节我们对特定情况的回应的基础。记忆形成可以在许多方面影响，这是强大的情绪状态之一。确实，在剧烈的情感环境中形成的记忆在我们的脑海中留下了深刻的烙印。记忆与情绪之间这种联系的神经生物学基础尚不清楚。可能涉及两个大脑区域：一方面，海马（HP）对于记忆形成至关重要，也参与情感行为，尤其是焦虑。另一方面，Raphe以处理与情绪相关的信息而闻名。使用神经递质谷氨酸并接触HP的Raphe神经元已被鉴定出来。对于这些谷氨酸能神经元及其在影响记忆形成或其他类型的HP相关行为中的作用知之甚少。该项目的目的是提供这种新颖的大脑通道的第一个深入特征，并揭示其在记忆形成和情感中的作用。该研究项目的第一个目的是确定谷氨酸能神经元在Raphe内投射到HP的特定定位，该谷物剂将提供有关其预期功能的信息。第二个目的是记录自由行为小鼠中HP预测的谷氨酸能神经元的活性，以揭示其活跃的行为时期。考虑到HP的作用已在空间记忆和焦虑中都得到了证明，将研究两种行为。将使用称为钙成像的技术记录活动模式，该技术可以简单地通过大量神经元中的荧光变化来可视化神经元活动。我们的建议的第二部分将揭示这些神经元与特定行为环境有关的活动。该研究项目的最终目的是操纵这种谷氨酸能途径的活性，以在谷氨酸能神经元活性和行为之间建立催化关系。这将使用一种称为光遗传学的技术来实现，该技术允许激活神经元或使用光线沉默。生成的结果将允许了解投射到HP的谷氨酸能Raphe神经元是否负责记忆形成或动画。当前，了解来自不同大脑区域的神经元如何共同交流以产生行为是神经科学研究的主要挑战。该项目通过尖端技术的结合来应对这一挑战，以揭示Raphe如何与HP通信以通过情绪状态调节记忆形成。因此，了解这种大脑机制是揭示我们的大脑如何“为重要的内容编码”的关键第一步。