CAREER:Coordination of neural activity during memory formation in humans

职业：人类记忆形成过程中神经活动的协调

• 批准号: 1554105
• 负责人: Ueli Rutishauser
• 金额: $ 62.3万
• 依托单位: Cedars-Sinai Medical Center
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1554105&HistoricalAwards=false
• 关键词: CAREER; Coordination; neural; activity; during

Memory disorders affect millions of Americans today. Despite decades of work, we have little ability to prevent, improve or treat such memory disorders. With the support of the National Science Foundation, Dr. Ueli Rutishauser and colleagues are investigating how humans form, store, and retrieve memories. The research supported by this CAREER award is to observe the electrical activity of brain cells in the hippocampus, an area essential for the formation of new memories. This research is performed with human patients who are undergoing surgery to treat epilepsy. To localize seizures, these patients are implanted with small wires in different parts of their brain, which allows researchers to investigate the human nervous system at the cellular level. Using this technique, we will investigate how human brain cells change when new memories are formed. Specifically, we will test whether the formation of new memories is dependent on a brain rhythm called the "theta oscillation", and if disruptions of this rhythm lead to poor memory. Critically, theta oscillations can be changed by electrical stimulation, which offers a potential technique to improve memory. Through education, teaching, and mentoring, this CAREER award will enable new researchers and organizations to take advantage of the extremely valuable opportunities for basic research on the human nervous system presented by intracranial electrophysiology. The research objective of this CAREER award is to investigate the neural mechanisms of human declarative memory at the level of individual neurons and circuits. We work with patients implanted with micro-wire electrodes who volunteer to participate in this research. The objective is to understand how the activity of networks of neurons is coordinated such that their collective action results in plasticity and long-term memories. We test the hypothesis that hippocampal theta oscillations mediate this process by combining human single-neuron recordings, behavioral testing, electrical stimulation, and computational modelling. This approach will allow us to assess the role and necessity of oscillations for the formation of human memories and thereby demonstrate the role of a specific oscillation in human cognition. We study i) how the activity of two distinct functional types of hippocampal neurons that we identified (visual and memory selective) are modulated by the theta rhythm; ii) how modulation of theta oscillations by shifts in spatial attention impacts individual neurons; and iii) whether there is a causal link between theta oscillations and memory strength. This study could provide, for the first time, a link between the cellular mechanisms of plasticity, oscillations, and human memory. The educational objective is to closely involve students in all aspects of the research, and to incorporate research results into classes, workshops and a K-12 outreach program. The resulting methods, tools, and datasets will be publicly released.

记忆障碍影响着今天数以百万计的美国人。尽管经过几十年的研究，我们几乎没有能力预防、改善或治疗这种记忆障碍。在国家科学基金会的支持下，Ueli Rutishauser博士和他的同事们正在研究人类如何形成、存储和检索记忆。这项职业奖支持的研究是观察海马区脑细胞的电活动，海马区是形成新记忆的关键区域。这项研究是在正在接受手术治疗癫痫的人类患者身上进行的。为了定位癫痫发作，这些患者在大脑的不同部分植入了细小的电线，这使得研究人员能够在细胞水平上研究人类神经系统。利用这项技术，我们将研究人类脑细胞在形成新记忆时的变化。具体地说，我们将测试新记忆的形成是否依赖于一种名为“theta振荡”的大脑节奏，以及这种节奏的中断是否会导致记忆力下降。关键的是，电刺激可以改变theta振荡，这为改善记忆提供了一种潜在的技术。通过教育、教学和指导，这一职业奖项将使新的研究人员和组织能够利用颅内电生理学为人类神经系统基础研究带来的极其宝贵的机会。这一职业奖的研究目标是在单个神经元和电路水平上研究人类陈述性记忆的神经机制。我们与植入微丝电极的患者合作，他们自愿参与这项研究。其目的是了解神经元网络的活动是如何协调的，从而使它们的集体行动产生可塑性和长期记忆。我们通过结合人类单神经元记录、行为测试、电刺激和计算模型来检验海马theta振荡介导这一过程的假设。这一方法将使我们能够评估振荡在人类记忆形成中的作用和必要性，从而展示特定振荡在人类认知中的作用。我们研究了i)我们识别的两种不同功能类型的海马神经元(视觉和记忆选择性)的活动如何受到theta节奏的调制；ii)空间注意力转移对theta振荡的调制如何影响单个神经元；iii)theta振荡和记忆强度之间是否存在因果联系。这项研究可能首次提供可塑性、振荡和人类记忆的细胞机制之间的联系。教育目标是让学生密切参与研究的各个方面，并将研究成果纳入课堂、研讨会和K-12推广计划。由此产生的方法、工具和数据集将公开发布。