Structural and Functional Plasticity Surrounding Implanted Neuroprostheses
植入神经假体周围的结构和功能可塑性
基本信息
- 批准号:10548226
- 负责人:
- 金额:$ 34.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-01-15 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdultAnti-Inflammatory AgentsAstrocytesAutopsyBasic ScienceBrainCellsCommunication BarriersCuesDataDendritic SpinesDetectionDevelopmentDevice DesignsDevicesElectric StimulationElectrodesElectrophysiology (science)EncapsulatedEnvironmentEquipment MalfunctionEventExcitatory SynapseExhibitsFluorescent DyesGliosisGlutamate TransporterGlutamatesImageImmunohistochemistryImplantImplanted ElectrodesIn VitroInflammatoryInflammatory ResponseInjuryInterruptionLabelLinkMeasurementMechanicsMediatingMethodsMicroelectrodesMicrogliaMicroscopeModelingMorphologyMotor CortexN-MethylaspartateNeocortexNervous System TraumaNeuronsNeurotransmittersNoiseOutcomePerformancePolymersPublishingRNA InterferenceRadialRattusRoleScanning Electron MicroscopyShapesSignal TransductionSiliconSliceSourceSurfaceSynapsesSynaptic TransmissionSynaptic plasticityTestingThinnessTimeTime StudyTissuesVertebral columnbiomaterial compatibilitybrain tissuecytokinecytotoxicitydensityelectric impedanceexcitotoxicityfunctional plasticitygamma-Aminobutyric Acidglial activationimplantable deviceimplantationimprovedin vivoinflammatory markerknock-downmicroscopic imagingneocorticalnervous system disorderneuron lossneuroprosthesisneurotoxicityneurotransmissionnovelpreservationresponsetransmission processtwo-photonvesicular GABA transportervesicular glutamate transporter 1
项目摘要
PROJECT SUMMARY
The development of implantable devices capable of recording or stimulating electrical activity in the brain has
created unprecedented opportunities to treat and study neurological diseases and injuries. However, a reactive
tissue response typically occurs following implantation which is widely believed to interfere with long-term device
performance. Inflammatory microglia and astrocytes encapsulate and isolate devices from neurons, while
neuronal signal sources are lost within the recordable radius of the electrode surface. While these observations
may contribute to signal instability and recording loss over time, the mechanistic link between specific
inflammatory events and changes in signal quality remains unclear. Our group is expanding upon the current
basic science understanding of device-tissue integration and recently published a study which showed shifts in
subtype-specific markers of synaptic transmission surrounding implanted electrode arrays. Our data indicated
an early elevation of markers of excitatory transmission (vesicular glutamate transporter-1, VGLUT1) three days
post-implantation that was followed by a subsequent shift to increased expression of labeling for inhibitory
neurotransmission (vesicular GABA transporter, VGAT). We hypothesize that structural and functional plasticity
of synaptic inputs surrounding devices could contribute to loss of recorded signals. We further hypothesize that
the timed elevation of glutamate and GABA release may act as “go” and “stop” cues which mediate the reactive
tissue response. In this proposal, we will build upon our initial observations, further investigating the underlying
mechanisms and functional consequences of synaptic plasticity on device performance. In Specific Aim 1, we
will define the functional impacts of glutamatergic synaptic remodeling at the electrode interface on recorded
signal quality and reactive gliosis. We will correlate transporter expression with signal quality and assess the
effects of VGLUT1 knockdown on signal quality and tissue response. In Specific Aim 2, we similarly will define
the functional impacts of GABAergic synaptic remodeling at the electrode interface on recorded signal quality
and reactive gliosis. We hypothesize that while early glutamate release may incite neurotoxicity and reactive
gliosis, subsequent GABA release acts in an anti-inflammatory capacity to preserve neuronal viability and
mitigate further glial reactivity. In Specific Aim 3, we will reveal structural plasticity in the dendritic arbors of
neurons at the electrode interface. For this aim, we will use two photon imaging to assess changes in dendritic
spine density and morphology surrounding devices captured in ex vivo brain tissue slices. For all aims, we will
test both silicon and polyimide-based arrays to compare results between device designs commonly used in the
field. We will inspect impedance measurements and post-mortem scanning electron microscopy images for signs
of device failure to strengthen the interpretation of our results. By exploring novel mechanisms of synaptic
plasticity surrounding implanted electrode arrays, we expect to open new opportunities to both understand, and
improve upon, long-term device function and biocompatibility.
项目总结
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)
Structural and functional changes of deep layer pyramidal neurons surrounding microelectrode arrays implanted in rat motor cortex.
植入大鼠运动皮层的微电极阵列周围的深层锥体神经元的结构和功能变化。
- DOI:10.1016/j.actbio.2023.07.027
- 发表时间:2023
- 期刊:
- 影响因子:9.7
- 作者:Gregory,BronsonA;Thompson,CortH;Salatino,JosephW;Railing,MiaJ;Zimmerman,ArianaF;Gupta,Bhavna;Williams,Kathleen;Beatty,JosephA;Cox,CharlesL;Purcell,ErinK
- 通讯作者:Purcell,ErinK
Toward guiding principles for the design of biologically-integrated electrodes for the central nervous system.
- DOI:10.1088/1741-2552/ab7030
- 发表时间:2020-03-12
- 期刊:
- 影响因子:4
- 作者:Thompson CH;Riggins TE;Patel PR;Chestek CA;Li W;Purcell E
- 通讯作者:Purcell E
Spatiotemporal patterns of gene expression around implanted silicon electrode arrays.
- DOI:10.1088/1741-2552/abf2e6
- 发表时间:2021-04-27
- 期刊:
- 影响因子:4
- 作者:Thompson CH;Saxena A;Heelan N;Salatino J;Purcell EK
- 通讯作者:Purcell EK
Differential Co-Expression Analysis of RNA-Seq Data Reveals Novel Potential Biomarkers of Device-Tissue Interaction.
RNA-seq数据的差异共表达分析揭示了设备组织相互作用的新型潜在生物标志物。
- DOI:10.1109/embc48229.2022.9871437
- 发表时间:2022-07
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Erin K Purcell其他文献
Erin K Purcell的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Erin K Purcell', 18)}}的其他基金
Spatial transcriptomics at the interface of implanted electrodes in the brain
大脑植入电极界面的空间转录组学
- 批准号:
10532895 - 财政年份:2022
- 资助金额:
$ 34.7万 - 项目类别:
Structural and Functional Plasticity Surrounding Implanted Neuroprostheses
植入神经假体周围的结构和功能可塑性
- 批准号:
10083770 - 财政年份:2019
- 资助金额:
$ 34.7万 - 项目类别:
Structural and Functional Plasticity Surrounding Implanted Neuroprostheses
植入神经假体周围的结构和功能可塑性
- 批准号:
10004761 - 财政年份:2019
- 资助金额:
$ 34.7万 - 项目类别:
Optical control of network formation in stem cell-derived neurons
干细胞源性神经元网络形成的光学控制
- 批准号:
9128745 - 财政年份:2015
- 资助金额:
$ 34.7万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 34.7万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 34.7万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 34.7万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 34.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 34.7万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 34.7万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 34.7万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 34.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 34.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 34.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)