NCS-FO: Investigation of cortical-hippocampal interaction during memory formation using multimodal recordings

学习和记忆是人类行为的核心认知功能。人们普遍假设，大脑的多个区域与皮质下结构海马体协调，形成学习和长期记忆的基础。了解学习过程中不同大脑区域是如何相互作用的，可以更好地理解大脑中的长期记忆存储。这个高风险、高回报的项目将通过多模式成像和记录实验，研究大脑皮质和海马体在学习和记忆巩固过程中如何沟通和协调信息传输。然而，由于技术限制，这样的实验目前并不可行。这一建议遵循了一种研究学习和记忆过程中海马-皮质协调的变革性方法，方法是结合(I)开发新型可植入探针的技术突破，(Ii)精心设计的多模式传感实验，以及(Iii)先进的数据分析技术。这种能力可能会导致在大脑中进行信息处理的发现，并可以帮助更好地了解电路功能障碍，这些功能会导致影响全球大量人口的各种神经疾病的记忆障碍。这项研究的发现有助于弥合人工智能驱动的学习模型和大脑中真正的生物学习之间的关键差距。对后者的理解有可能重塑当前机器学习的实践。该项目还将为学生提供从事微细加工、神经科学和数据分析方面的前沿多学科研究的机会。该项目还将为工程学中代表性较低的少数族裔提供研究实习机会和指导倡议。该项目的目标是通过多模式成像和记录实验，研究大脑皮质和海马体在学习和记忆巩固过程中如何沟通和协调信息传输。广域钙成像将用于监测清醒小鼠大范围皮质神经的激活。来自海马体的同步电生理记录将检测到高频振荡，如来自单个神经元的尖锐波纹和尖峰。多种成像和记录方式的集成需要开发新的植入式探头技术，使其能够在成像过程中从海马区进行记录，并需要先进的数据分析技术。将利用研究人员的互补专业知识进行以下工作：任务1：开发与光学成像兼容的新型灵活穿透微探针；任务2：在清醒的小鼠中进行多模式、多尺度实验，以协同结合来自钙荧光、局部场电位、单个单位和行为的信息，以及任务3：开发一种新颖的数据驱动的任务感知算法，以使用来自皮质的多模式钙成像和来自海马区的电生理记录执行单事件分析。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Learning and memory are cognitive functions that are central to human behavior. It has been widely hypothesized that multiple brain regions are coordinated with hippocampus, a subcortical structure, to form the basis for learning and long-term memory. Understanding how different brain regions interact during learning can lead to better understanding of long-term memory storage in the brain. This high-risk, high-payoff project will investigate how cortex and hippocampus communicate and coordinate information transfer during learning and memory consolidation by multimodal imaging and recording experiments. However, such experiments are not currently feasible due to technical limitations. This proposal follows a transformative approach to investigate hippocampus-cortex coordination during learning and memory by combining (i) technological breakthroughs in development of novel implantable probes, (ii) carefully designed multi-modal sensing experiments, and (iii) advanced data analysis techniques. Such a capability could lead to discoveries on information processing in the brain and can help to better understand circuit dysfunctions causing memory impairment for various neurological disorders affecting a large population worldwide. Findings from this research can help with bridging critical gaps between artificial intelligence-driven models for learning and real biological learning in brain. Understanding the latter has the potential to reshape current practices in machine learning. This project will also provide opportunities for students to become engaged in cutting-edge multidisciplinary research in microfabrication, neuroscience and data analysis. The project will also provide research internship opportunities and mentoring initiatives for underrepresented minorities in engineering.The objective of this project is to investigate how cortex and hippocampus communicate and coordinate information transfer during learning and memory consolidation by multimodal imaging and recording experiments. Wide-field calcium imaging will be used to monitor cortex-wide neural activation across large areas in awake mice. Simultaneous electrophysiological recordings from hippocampus will detect high frequency oscillations such as sharp-wave ripples and spikes from single neurons. Integration of multiple imaging and recording modalities requires development of new implantable probe technologies enabling recording from hippocampus during imaging and advanced data analysis techniques. Complementary expertise of the investigators will be leveraged to pursue; Task 1: Development of new flexible penetrating microprobes compatible with optical imaging, Task 2: Multi-modal, multi-scale experiments in awake mice generating brand new data sets synergistically combining information from calcium fluorescence, local field potentials, single units and behavior, and Task 3: Development of a novel data-driven task-aware algorithm to perform single-event analyses with multimodal calcium imaging from cortex and electrophysiological recordings from hippocampus.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.