Retrosplenial Circuits Underlying Landmark Stability

压后回路是地标稳定性的基础

• 批准号: 10362569
• 负责人: Dhruba Banerjee
• 金额: $ 5.18万
• 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/10362569
• 关键词: Anatomy; Animals; Area; Behavior assessment; Behavioral; Brain; Brain region; Calcium; Cells; Communities; Data; Disease; Disinhibition; Environment; Functional Imaging; Functional disorder; Head; Health; Hippocampal Formation; Hippocampus (Brain); Human; Human body; Image; Immersion; 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; virtual reality environment; virtual reality system; 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.

项目总结 视觉是空间导航的关键，因为视觉地标引导着我们的日常生活。 然而，一些地标变得不可靠，因为它们会随着时间的推移而改变位置。最新研究 提示大脑中一个称为脾后皮质的区域处理标志物并评估它们的 稳定性1.脾后皮质位于海马体结构之间的连接处，海马体结构是 导航、学习和记忆--还有视觉皮质。解剖和功能上的联系有 提示脾后皮质在一段时间内是视觉空间加工的部位2。事实上，患有这种疾病的患者 对RSC的损害很难利用地标在熟悉的环境中导航，学习新的 路线，以及执行视觉记忆任务3。但直到最近才在小鼠体内发现了“位置”细胞 脾后皮质，它编码了动物在世界上的位置。我们的初步数据显示，将细胞 当一只动物在视觉、虚拟现实的赛道上奔跑时，可以看到。我们假设这些地方 制图表达可能会受到局部地标移动的强烈影响，从而对这两个空间进行编码 和里程碑式的稳定性。这项提议提出了一种使用体内双光子来检验这一假说的策略 钙成像和身临其境的虚拟现实环境。首先，该提案旨在充分说明 脾后“部位”细胞的视觉特性。其次，该提案旨在测试高海拔地区是否存在 标志性不稳定性由较少的位置字段编码。最后，该提案关注的是具有里程碑意义的时刻 开始移动，看看神经回路是否显示出变得可塑性的迹象。科学家们长期以来一直对此感兴趣 大脑是如何实现空间导航的。空间导航不仅是日常生活所必需的，神经也是如此 所涉及的电路与处理学习和记忆的大脑区域显著重叠。如果成功，这将是 研究将深入了解导航的神经回路和视觉地标的基本贡献 正在处理。这些结果将为这些电路如何在健康状态下工作以及它们为什么会正常工作增加基本知识 容易受到神经变性和中风等疾病的影响。该项目还将向科学和 医学界对用于行为评估的沉浸式感觉界面的正确设计 动物和潜在的人类康复疗法。