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，大脑的多个区域与海马体（一种皮层下结构）协调，形成了学习和长期记忆的基础。了解不同的大脑区域在学习过程中是如何相互作用的，可以更好地理解大脑中的长期记忆储存。这个高风险、高回报的项目将通过多模态成像和记录实验来研究大脑皮层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递。然而，由于技术限制，这种实验目前还不可行。本研究采用了一种变革性的方法，通过结合(i)新型植入式探针的技术突破，（ii）精心设计的多模态传感实验，以及（iii）先进的数据分析技术，来研究学习和记忆过程中海马体-皮层的协调。这种能力可能会导致大脑信息处理的发现，并有助于更好地理解导致记忆障碍的电路功能障碍，以及影响全球大量人口的各种神经系统疾病。这项研究的发现可以帮助弥合人工智能驱动的学习模型与真正的大脑生物学习之间的关键差距。理解后者有可能重塑当前机器学习的实践。该项目还将为学生提供参与微制造、神经科学和数据分析等前沿多学科研究的机会。该项目还将为工程领域未被充分代表的少数族裔提供研究实习机会和指导计划。本项目旨在通过多模态成像和记录实验研究学习记忆巩固过程中大脑皮层和海马间的信息交流和协调。宽视场钙成像将用于监测清醒小鼠大面积的全皮质神经激活。同时，海马体的电生理记录将检测到单个神经元的高频振荡，如尖波波纹和尖峰。多种成像和记录模式的集成需要开发新的植入式探针技术，以便在成像过程中从海马体记录和先进的数据分析技术。将利用调查人员的互补专业知识进行调查；任务1：开发与光学成像兼容的新型柔性渗透微探针；任务2：在清醒小鼠中进行多模态、多尺度实验，生成全新的数据集，协同结合钙荧光、局部场电位、单个单元和行为等信息；任务3：开发一种新的数据驱动的任务感知算法，利用来自皮质的多模态钙成像和来自海马体的电生理记录进行单事件分析。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.