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.

该奖项是根据2021年《美国救援计划法》（公法117-2）全部或部分资助的。大脑是一种器官，可存储，比较和解释有关身体状况的信息以及生物如何与环境相互作用。有大量有关生物体可用的物体，时间，空间和事件的信息。但是，大脑的存储能力以及可以一次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，并选择给定时间点最适用的优先级。控制它的大脑大脑区域之间的这种机制和连接仍然很少理解。这项研究将研究与新颖性检测有关的两个关键大脑区域如何共同进行连续分类并确定要存储在不断变化的环境中的信息。这项研究将通过提高我们对正常国家认知的知识和理解来对社会产生广泛的影响。这项研究将通过阐明特定细胞类型在学习中的作用以及其失调如何导致神经系统疾病的作用，从而进一步产生更广泛的影响。最后，这项研究旨在通过支持学生对尖端技术的培训来增加参与STEM的参与，这些技术可以广泛应用于生物医学科学研究和行业。VTA和Hippocampus（CA1）之间的Reciprocal联系形成了一个循环，该环路控制了新颖的检测。虽然VTA含有多巴胺，谷氨酸和GABA神经元，但环路的功能主要归因于VTA多巴胺投影。这项研究的目的是剖析VTA谷氨酸预测对海马的功能意义，及其在新颖性学习和背景区分中的作用。为了实现这一目标，中性记录将与自由行为的小鼠CA1中VTA终端的光遗传学调制结合使用。此方法将创建前提来解决两个主要目标。 （1）确定VTA-CA1道在工作内存和上下文的CA1集成中的功能。 （2）确定VTA突触前输入在CA1锥体细胞互助同步中的作用。这项研究将填补对主管新颖学习和背景歧视行为的神经回路的知识和理解的空白。在行为任务期间，将部署尖端的遗传和电子工具以靶向和调节小鼠CA1中的VTA终端。执行这些实验将显着增加对VTA-Hampocampus环内细胞特异性投影的理解。它还将阐明传统对VTA多巴胺投影的关注所忽略的细胞特异性中性电路的功能。该奖项反映了NSF的法定任务，并通过基金会的智力优点和更广泛的影响标准通过评估来诚实地支持支持。