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

记忆塑造行为;它们是构成我们生活经历记录的基石，并调节我们对特定情况的反应。记忆的形成可以受到多种方式的影响，其中最强的一种是情绪状态。事实上，在沉重的情感背景下形成的记忆在我们的脑海中留下了强烈的印记。记忆和情绪之间联系的神经生物学基础仍然不清楚。两个大脑区域可能参与其中：一方面，海马体（HP）被认为是记忆形成的关键，也参与了情绪行为，特别是焦虑;另一方面，中缝是众所周知的处理情绪相关信息。最近已经鉴定出使用神经递质谷氨酸并接触HP的中缝神经元。关于这些海马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，我们知之甚少。该项目的目标是提供这种新的大脑通路的第一个深入表征，并揭示其在记忆形成和情感中的作用。* 本研究项目的第一个目的是确定投射到中缝内HP的多巴胺能神经元的特定定位，这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投射的神经元的活动，以解开它们活跃的行为期。考虑到HP在空间记忆和焦虑中的作用已被证明，这两种类型的行为将被研究。活动模式将使用称为钙成像的技术记录，该技术允许通过同时在大量神经元中的荧光变化来可视化神经元活动。我们建议的第二部分将揭示这些神经元何时与特定的行为环境相关。本研究项目的最终目的是操纵这条神经元通路的活动，以建立神经元活动和行为之间的因果关系。这将使用一种称为光遗传学的技术来实现，该技术允许使用光激活神经元或使其沉默。所产生的结果将允许理解投射到HP的突触能中缝神经元是否负责记忆形成或焦虑。了解来自不同大脑区域的神经元如何相互通信以产生行为是目前神经科学研究的主要挑战。这个项目使用尖端技术的组合来解决这一挑战，以揭示中缝如何与HP沟通，通过情绪状态调节记忆的形成。因此，了解这种大脑机制是揭示我们的大脑如何“编码重要事物”的关键第一步。

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”.