Retrosplenial Circuits Underlying Landmark Stability

压后回路是地标稳定性的基础

• 批准号: 9761231
• 负责人: Dhruba Banerjee
• 金额: $ 3.99万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9761231
• 关键词: Anatomy; Animals; Area; Behavior assessment; Behavioral; Brain; Brain region; Calcium; Cells; Communities; Data; Disease; Disinhibition; Environment; Functional Imaging; Functional disorder; Gap Junctions; Head; Health; Hippocampal Formation; Hippocampus (Brain); Human; Human body; Image; Immersion Investigative Technique; Knowledge; Lead; Learning; Life; Location; Medical; Medicine; Memory; Monitor; Movement; Mus; Nerve Degeneration; Neurologic; Neurosciences; Patients; Population; Positioning Attribute; Process; Property; Rehabilitation therapy; Research; Role; Rotation; Route; Running; Scientist; Sensory; Site; Stroke; Structure; Synapsins; System; Tablets; Tactile; Testing; Time; Training; Translating; Traumatic Brain Injury; Trees; Vision; Visual; Visual Cortex; Visual impairment; Visuospatial; adeno-associated viral vector; base; cell cortex; cellular imaging; density; design; excitatory neuron; experience; experimental study; imaging study; in vivo calcium imaging; inhibitory neuron; insight; interest; mouse model; neural circuit; place fields; promoter; relating to nervous system; temporal measurement; tool; two-photon; virtual; virtual reality; visual memory; way finding

PROJECT SUMMARY Vision is key to spatial navigation, because visual landmarks guide us through our everyday lives. However, some landmarks become unreliable because they shift their location over time. Recent research suggests an area of the brain known as the retrosplenial cortex processes landmarks and evaluates their stability1. The retrosplenial cortex lies at a nexus between the hippocampal formation—a structure critical for navigation, learning, and memory—and the visual cortex. The anatomical and functional connections have suggested retrosplenial cortex is a site of visuospatial processing for some time2. And in fact, patients with damage to RSC have difficulty utilizing landmarks to navigate through familiar environments, learning new routes, and performing visual memory tasks3. But only recently have “place” cells been discovered in mouse retrosplenial cortex, which encode the animal’s position in the world4. Our preliminary data suggest place cells can be seen while an animal runs through a visual, virtual-reality track. We hypothesized that these place representations may be strongly influenced by the movement of local landmarks, thus encoding both space and landmark stability. This proposal lays out a strategy for testing this hypothesis using in vivo two-photon calcium imaging and immersive virtual reality environments. First the proposal aims to fully characterize the visual properties of retrosplenial “place” cells. Second, the proposal aims to test whether areas of high landmark instability are encoded by fewer place fields. Finally, the proposal focuses on the moment a landmark begins moving to see if the neural circuits show signs of becoming plastic. Scientists have long been interested in how the brain enables spatial navigation. Not only is spatial navigation essential to daily life, but the neural circuits involved overlap significantly with brain regions that process learning and memory. If successful, this study will generate insight into the neural circuits of navigation and the essential contribution of visual landmark processing. These results will add basic knowledge into how these circuits function in health and why they are vulnerable to diseases such as neurodegeneration and stroke. The project will also inform the scientific and medical communities on the proper design of immersive sensory interfaces for behavioral assessment in animals and potentially rehabilitative therapies in humans.

项目摘要 视觉是空间导航的关键，因为视觉地标在我们的日常生活中引导我们。 然而，一些地标变得不可靠，因为它们随着时间的推移而改变位置。最近的研究 表明大脑中一个被称为压后皮质的区域处理标志物，并评估它们的 稳定性1.压后皮质位于海马结构之间的连接处，海马结构是一个关键的结构， 导航、学习和记忆以及视觉皮层。解剖和功能上的联系 提示压后皮质是一段时间内的视觉空间处理部位2。事实上， RSC的损伤很难利用地标在熟悉的环境中导航，学习新的 路线，并执行视觉记忆任务3.但直到最近才在老鼠身上发现了“位置”细胞 压后皮质，编码动物在世界上的位置4。我们的初步数据显示定位细胞 当动物跑过一个视觉的虚拟现实的轨道时，我们假设这些地方 表示可能会受到局部地标的移动的强烈影响，因此对空间 和地标稳定性。该提案提出了一种使用体内双光子技术来检验这一假设的策略。 钙成像和沉浸式虚拟现实环境。首先，该提案旨在充分描述 压后“位置”细胞的视觉特性。其次，该提案旨在测试高风险地区是否 界标不稳定性由较少的位置字段编码。最后，该建议侧重于一个里程碑时刻 开始移动，看看神经回路是否有变得可塑的迹象。科学家们一直对 大脑是如何进行空间导航的。空间导航不仅对日常生活至关重要， 所涉及的回路与处理学习和记忆的大脑区域明显重叠。如果成功，这 这项研究将深入了解导航的神经回路和视觉地标的重要作用 处理.这些结果将为这些回路在健康中如何发挥作用以及为什么它们会这样做增加基础知识。 易患神经退化和中风等疾病。该项目还将向科学和 医学界对行为评估的沉浸式感觉界面的适当设计， 动物和潜在的人类康复疗法。