A universal and 3D-printed rat calvarium replacement system to enable for pan-cortical and sub-cortical recordings and optogenetics

通用 3D 打印大鼠颅骨替换系统，可实现全皮层和皮层下记录和光遗传学

• 批准号: 10054940
• 负责人: Brendon O Watson
• 金额: $ 42.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054940
• 关键词: 3-Dimensional; 3D Print; Address; Anatomy; Animals; Behavior; Biology; Brain; Brain Diseases; Brain region; Calcium; Cell Nucleus; Cells; Chronic stress; Communities; Complex; Complication; Coupled; Custom; Data; Devices; Disease; Distant; Dorsal; Electrodes; Electrophysiology (science); Elements; Engineering; Event; Fiber Optics; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Health; Hippocampus (Brain); Human; Image; Implant; Implanted Electrodes; Lead; Major Depressive Disorder; Measures; Mechanics; Medial Dorsal Nucleus; Methods; Modeling; Nature; Neocortex; Neurobiology; Neurons; Neurophysiology - biologic function; Neurosciences; Operative Surgical Procedures; Output; Patients; Play; Positioning Attribute; Rattus; Records Controls; Research; Resolution; Rodent; Rodent Model; Role; Sampling; Secure; Silicon; Site; Sleep; Stress; Structure; Surface; Synapses; Synaptic Transmission; System; Techniques; Technology; Testing; Thalamic structure; Vision; Work; base; biological adaptation to stress; cranium; design; experimental study; flexibility; implantation; innovation; insight; millisecond; neocortical; neuroregulation; new technology; new therapeutic target; novel; novel strategies; optogenetics; relating to nervous system; response; temporal measurement; tool; 3-Dimensional; 3D Print; Address; Anatomy; Animals; Behavior; Biology; Brain; Brain Diseases; Brain region; Calcium; Cell Nucleus; Cells; Chronic stress; Communities; Complex; Complication; Coupled; Custom; Data; Devices; Disease; Distant; Dorsal; Electrodes; Electrophysiology (science); Elements; Engineering; Event; Fiber Optics; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Health; Hippocampus (Brain); Human; Image; Implant; Implanted Electrodes; Lead; Major Depressive Disorder; Measures; Mechanics; Medial Dorsal Nucleus; Methods; Modeling; Nature; Neocortex; Neurobiology; Neurons; Neurophysiology - biologic function; Neurosciences; Operative Surgical Procedures; Output; Patients; Play; Positioning Attribute; Rattus; Records Controls; Research; Resolution; Rodent; Rodent Model; Role; Sampling; Secure; Silicon; Site; Sleep; Stress; Structure; Surface; Synapses; Synaptic Transmission; System; Techniques; Technology; Testing; Thalamic structure; Vision; Work; base; biological adaptation to stress; cranium; design; experimental study; flexibility; implantation; innovation; insight; millisecond; neocortical; neuroregulation; new technology; new therapeutic target; novel; novel strategies; optogenetics; relating to nervous system; response; temporal measurement; tool

Abstract While altered broad-scale brain dynamics are a key brain signature of major depressive disorder (MDD) and despite the plethora of powerful neuroscientific tools available in rodents, we actually do not currently have the capacity to assess these broad-scale neocortical dynamics in rodents with synaptic-timescale temporal and single neuron resolution. This is a key gap in the capacity of neuroscientists to study MDD-related biology via rodent models including the sustained threat model. Electrophysiologic and optogenetic approaches would be ideal to study how neocortical dynamics are orchestrated at baseline and are perturbed in disease, since many mechanisms may be synaptic in nature and both methods can operate at synaptic-timescales. We are a team of neuroscientists and mechanical engineers and we aim to develop a system to allow implantation of previously- impractical complex combinations of electrodes and optic fibers to record and manipulate the rat brain. The basis of our approach is a 3-dimensionally printed (3D printed) replacement for the dorsal rat skull – an “Interface Plate” - which we have already successfully attached to two rats with good survival. Unlike a natural skull the Interface Plate is custom designed and fabricated and so can be adapted to guide and secure many devices to the animal using a novel surgical approach including pre-surgical assembly. We aim to optimize our design for the Interface Plate to enable two experiments that will be novel and crucial to studies of sustained threat-related disturbances in neocortical dynamics. The first aim will use our 3D printed positioning and guide system to place 128 electrodes broadly across the entire dorsal neocortex. This will enable the first ever mapping of electrical activity at sub-millisecond resolution across the entire dorsal neocortex enabling us to capture events ranging from synaptic transmission to oscillations to neuromodulation, behavior and brain state transitions. We will additionally place electrodes at both superficial and deep layers to gather data about relative roles of these evolutionarily-conserved anatomical layers. In a second aim we will adapt our Interface Plate to enable recording in neocortex while simultaneously recording and optogenetically stimulating regions that play key roles in coordinating neocortex including the dorsal hippocampus, the medial dorsal nucleus of the thalamus (MDN) and the thalamic reticular nucleus (TRN). In this aim, 8 (and later 32) electrodes will be implanted in cortex for recording while into dorsal hippocampal CA1, MDN and TRN we will implant silicon probes with 64 recording channels and a coupled optic fiber. This will facilitate experiments examining and testing the roles of non- neocortical structures in coordinating the cortex both in and out of sustained threat conditions. The experiments enabled here will provide fundamental new data regarding the neocortex in health and disease. This work will also lead to the creation of a customizable and flexible new tool which we will make openly available to enable complex experiments in freely behaving animals for anyone in the neuroscience community.

抽象的 虽然大规模脑动力学改变是重度抑郁症（MDD）的关键大脑签名，并且 尽管啮齿动物中有大量强大的神经科学工具，但实际上我们目前没有 评估合成时间临时性和 单神经元分辨率。这是神经科学家通过通过 啮齿动物模型，包括持续威胁模型。电生理和光遗传学方法将是 非常适合研究新皮质动力学如何在基线上精心策划并在疾病中受到干扰，因为许多 机制本质上可以是突触的，两种方法都可以在突触时刻度运行。我们是一个团队 神经科学家和机械工程师的旨在开发一个系统以允许植入以前的 电极和光纤的不切实际复杂组合记录和操纵大鼠脑。这 我们方法的基础是背鼠头骨的3维打印（3D打印）替代品 - 一个“接口 板” - 我们已经成功地依附于两只老鼠，生存良好。与自然头骨不同 界面板是定制和制造的，因此可以适应并将许多设备固定到 动物使用一种新型的手术方法，包括外科组装。我们旨在优化我们的设计 界面板使两个实验对持续威胁相关的研究至关重要，这些实验将是新颖的 新皮质动力学的干扰。第一个目标将使用我们的3D打印定位和指南系统来放置 在整个背侧新皮层中广泛的128个电子。这将启用有史以来的第一个电气映射 在整个背侧新皮层的亚毫秒分辨率下的活动，使我们能够捕获范围的事件 从突触传播到振荡到神经调节，行为和大脑状态转变。我们将 此外，将电极放在浅层和深层，以收集有关这些相对作用的数据 进化保存的解剖层。在第二个目标中，我们将调整接口板以启用录音 在新皮层中，同时记录和光遗传学刺激区域，在 在包括背侧海马，丘脑内侧核（MDN）和 丘脑网状核（TRN）。在此目的中，8（后来的32）电子将植入皮质中 记录到背部海马CA1，MDN和TRN时，我们将使用64个记录植入硅问题 通道和耦合光纤。这将促进研究和测试非 - 的作用的实验 在协调中的新皮层结构内外持续的威胁条件下的皮质。实验 在此处启用将提供有关健康和疾病新皮层的基本新数据。这项工作将 也导致创建可自定义且灵活的新工具，我们将公开使用该工具以启用 为神经科学社区中的任何人，在自由表现动物中进行复杂的实验。