Unraveling VTA modulation of hippocampal encoding

解开海马编码的 VTA 调节

• 批准号: 2137023
• 负责人: Olalekan Ogundele
• 金额: $ 54.84万
• 依托单位: Louisiana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2137023&HistoricalAwards=false
• 关键词: Unraveling; VTA; modulation; hippocampal; encoding

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).The brain is an organ that stores, compares, and interprets information about the state of the body, and how organisms interact with their environment. There is a wealth of information about objects, time, space, and events available to the organism. However, the storage capacity of the brain, and the volume of information that can be processed – at once – is limited. For this reason, there is a need for the brain to assign priority levels to environmental stimuli and select what is most applicable at a given time point. This mechanism and connections between the brain regions of the brain that controls it are still poorly understood. This research will investigate how two key brain regions concerned with novelty detection work together to continuously classify and prioritize the information to be stored in a continuously changing environment. This research will have a broad impact on society by increasing our knowledge and understanding of cognition in normal states. This research will further have broader impacts by elucidating the role of specific cell types in learning, and how their dysregulation can lead to neurological disorders. Lastly, this research is designed to increase participation in STEM by facilitating the training of students in cutting-edge techniques that can be applied broadly in biomedical science research and industries.Reciprocal connection between the VTA and hippocampus (CA1) forms a loop that governs novelty detection. While the VTA contains dopamine, glutamate, and GABA neurons, the function of the loop has been primarily attributed to the VTA dopamine projections. The goal of this research is to dissect the functional significance of VTA glutamate projections to the hippocampus, and their role in novelty learning and context discrimination. To achieve this goal, neural recording will be combined with optogenetic modulation of VTA terminals in the CA1 of freely behaving mice. This method will create the premise to address two main objectives; (1) Determine the function of the VTA-CA1 tract in CA1 integration of working memory and context. (2) Ascertain the role of VTA presynaptic inputs in CA1 pyramidal cell-interneuron synchrony. This research will fill gaps in the knowledge and understanding of neural circuits that govern novelty learning and context discrimination behavior. Cutting-edge genetic and electronic tools will be deployed to target and modulate VTA terminals in the CA1 of mice during behavioral tasks. Performing these experiments will significantly increase the understanding of cell-specific projections within the VTA-hippocampus loop. It will also elucidate the function of cell-specific neural circuits that have been overlooked by a traditional focus on VTA dopamine projections.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项全部或部分由2021年美国救援计划法案（公法117-2）资助。大脑是一个器官，储存，比较和解释有关身体状态的信息，以及生物体如何与环境相互作用。生物体可以获得大量关于物体、时间、空间和事件的信息。然而，大脑的存储容量以及可以立即处理的信息量是有限的。因此，大脑需要为环境刺激分配优先级，并选择在给定时间点最适用的刺激。这种机制和控制它的大脑区域之间的连接仍然知之甚少。这项研究将研究与新奇检测有关的两个关键大脑区域如何共同工作，以不断分类和优先考虑在不断变化的环境中存储的信息。这项研究将通过增加我们对正常状态下认知的知识和理解对社会产生广泛的影响。这项研究将进一步阐明特定细胞类型在学习中的作用，以及它们的失调如何导致神经系统疾病，从而产生更广泛的影响。最后，本研究的目的是通过培养能够广泛应用于生物医学科学研究和产业的尖端技术，提高学生对STEM的参与度。腹侧被盖区和海马体（CA 1）之间的相互连接形成了一个控制新奇检测的回路。虽然腹侧被盖区含有多巴胺、谷氨酸和GABA神经元，但环的功能主要归因于腹侧被盖区的多巴胺投射。本研究的目的是剖析腹侧被盖区谷氨酸投射到海马的功能意义，以及它们在新奇学习和上下文辨别中的作用。为了实现这一目标，神经记录将与自由行为小鼠的CA 1中VTA末端的光遗传学调节相结合。该方法为解决以下两个主要问题创造了前提：（1）确定VTA-CA 1束在工作记忆和上下文的CA 1整合中的功能。(2)明确腹侧被盖区突触前传入在海马CA 1区锥体细胞-中间神经元同步性中的作用。这项研究将填补知识和理解的空白，控制新奇学习和上下文歧视行为的神经回路。尖端的遗传和电子工具将被部署到目标和调节VTA终端在CA 1小鼠在行为任务。进行这些实验将显着增加了解腹侧被盖区-海马环内的细胞特异性投射。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。