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
基本信息
- 批准号:10054940
- 负责人:
- 金额:$ 42.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:3-Dimensional3D PrintAddressAnatomyAnimalsBehaviorBiologyBrainBrain DiseasesBrain regionCalciumCell NucleusCellsChronic stressCommunitiesComplexComplicationCoupledCustomDataDevicesDiseaseDistantDorsalElectrodesElectrophysiology (science)ElementsEngineeringEventFiber OpticsFoundationsFunctional Magnetic Resonance ImagingFutureGoalsHealthHippocampus (Brain)HumanImageImplantImplanted ElectrodesLeadMajor Depressive DisorderMeasuresMechanicsMedial Dorsal NucleusMethodsModelingNatureNeocortexNeurobiologyNeuronsNeurophysiology - biologic functionNeurosciencesOperative Surgical ProceduresOutputPatientsPlayPositioning AttributeRattusRecords ControlsResearchResolutionRodentRodent ModelRoleSamplingSecureSiliconSiteSleepStressStructureSurfaceSynapsesSynaptic TransmissionSystemTechniquesTechnologyTestingThalamic structureVisionWorkbasebiological adaptation to stresscraniumdesignexperimental studyflexibilityimplantationinnovationinsightmillisecondneocorticalneuroregulationnew technologynew therapeutic targetnovelnovel strategiesoptogeneticsrelating to nervous systemresponsetemporal measurementtool
项目摘要
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
虽然广泛的大脑动力学改变是重度抑郁症(MDD)和
尽管啮齿类动物有大量强大的神经科学工具,但我们目前实际上还没有
通过突触时间尺度时间和时间来评估啮齿类动物的这些大范围的新皮质动态的能力
单神经元分辨率。这是神经科学家通过以下方式研究 MDD 相关生物学能力的一个关键差距:
啮齿动物模型,包括持续威胁模型。电生理学和光遗传学方法将是
非常适合研究新皮质动力学在基线时如何协调以及在疾病中如何受到干扰,因为许多
机制本质上可能是突触的,并且两种方法都可以在突触时间尺度上操作。我们是一个团队
由神经科学家和机械工程师组成,我们的目标是开发一种系统,允许植入先前的-
电极和光纤的复杂组合来记录和操纵大鼠大脑是不切实际的。这
我们方法的基础是用 3D 打印(3D 打印)替代大鼠背侧头骨——一个“界面”
“板”——我们已经成功地将其附着在两只存活良好的老鼠身上。与天然头骨不同的是,
接口板是定制设计和制造的,因此可用于引导和固定许多设备
该动物使用一种新颖的手术方法,包括手术前组装。我们的目标是优化我们的设计
接口板可实现两项实验,这对于持续威胁相关的研究来说是新颖且至关重要的
新皮质动力学紊乱。第一个目标将使用我们的 3D 打印定位和引导系统来放置
128 个电极广泛分布于整个背侧新皮质。这将实现有史以来第一次电力测绘
整个背侧新皮质以亚毫秒分辨率的活动使我们能够捕捉范围广泛的事件
从突触传递到振荡,再到神经调节、行为和大脑状态转换。我们将
另外,在表层和深层放置电极,以收集有关这些电极相对作用的数据
进化上保守的解剖层。第二个目标是我们将调整接口板以实现记录
在新皮质中,同时记录和光遗传学刺激区域,这些区域在
协调新皮质,包括背侧海马、丘脑背内侧核(MDN)和
丘脑网状核(TRN)。为了实现这一目标,将在皮质中植入 8 个(后来是 32 个)电极
在背侧海马 CA1、MDN 和 TRN 中进行记录,我们将植入具有 64 个记录的硅探针
通道和耦合光纤。这将有助于实验检查和测试非
新皮质结构在持续威胁条件下协调皮质。实验
此处启用将提供有关健康和疾病中新皮质的基本新数据。这项工作将
还导致创建一个可定制且灵活的新工具,我们将公开提供该工具以实现
为神经科学界的任何人进行自由行为动物的复杂实验。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Manufacturing Processes of Implantable Microelectrode Array for In Vivo Neural Electrophysiological Recordings and Stimulation: A State-Of-the-Art Review.
用于体内神经电生理记录和刺激的植入式微电极阵列的制造工艺:最先进的综述。
- DOI:10.1115/1.4063179
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Yi,Dongyang;Yao,Yao;Wang,Yi;Chen,Lei
- 通讯作者:Chen,Lei
3D Printed Skull Cap and Benchtop Fabricated Microwire-Based Microelectrode Array for Custom Rat Brain Recordings.
- DOI:10.3390/bioengineering9100550
- 发表时间:2022-10-14
- 期刊:
- 影响因子:4.6
- 作者:Yi, Dongyang;Hartner, Jeremiah P.;Ung, Brian S.;Zhu, Harrison L.;Watson, Brendon O.;Chen, Lei
- 通讯作者:Chen, Lei
Flexible High-Resolution Force and Dimpling Measurement System for Pia and Dura Penetration During In Vivo Microelectrode Insertion Into Rat Brain.
- DOI:10.1109/tbme.2021.3070781
- 发表时间:2021-08
- 期刊:
- 影响因子:0
- 作者:Chen L;Hartner J;Dong T;Li A;Watson B;Shih A
- 通讯作者:Shih A
Repurposing Cholinesterase Inhibitors as Antidepressants? Dose and Stress-Sensitivity May Be Critical to Opening Possibilities.
- DOI:10.3389/fnbeh.2020.620119
- 发表时间:2020
- 期刊:
- 影响因子:3
- 作者:Fitzgerald PJ;Hale PJ;Ghimire A;Watson BO
- 通讯作者:Watson BO
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Brendon O Watson其他文献
Brendon O Watson的其他文献
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{{ truncateString('Brendon O Watson', 18)}}的其他基金
Electrophysiologic characterization of circadian rhythms of prefrontal cortical network states in a diurnal rodent
昼夜啮齿动物前额皮质网络状态昼夜节律的电生理学特征
- 批准号:
10556475 - 财政年份:2023
- 资助金额:
$ 42.9万 - 项目类别:
Digital behavioral phenotyping and multi-region electrophysiology to determine behavioral and neural network changes underlying the stress response in mice
数字行为表型和多区域电生理学,以确定小鼠应激反应背后的行为和神经网络变化
- 批准号:
10397657 - 财政年份:2021
- 资助金额:
$ 42.9万 - 项目类别:
Digital behavioral phenotyping and multi-region electrophysiology to determine behavioral and neural network changes underlying the stress response in mice
数字行为表型和多区域电生理学,以确定小鼠应激反应背后的行为和神经网络变化
- 批准号:
10199475 - 财政年份:2021
- 资助金额:
$ 42.9万 - 项目类别:
Digital behavioral phenotyping and multi-region electrophysiology to determine behavioral and neural network changes underlying the stress response in mice
数字行为表型和多区域电生理学,以确定小鼠应激反应背后的行为和神经网络变化
- 批准号:
10577805 - 财政年份:2021
- 资助金额:
$ 42.9万 - 项目类别:
Role of waking activity in determining sleep-based modification of cortical circuits
清醒活动在确定基于睡眠的皮质回路修改中的作用
- 批准号:
9473810 - 财政年份:2017
- 资助金额:
$ 42.9万 - 项目类别:
Role of waking activity in determining sleep-based modification of cortical circuits
清醒活动在确定基于睡眠的皮质回路修改中的作用
- 批准号:
8948537 - 财政年份:2015
- 资助金额:
$ 42.9万 - 项目类别:
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