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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：
Erin K Purcell
金额：
$ 34.7万
依托单位：
MICHIGAN STATE UNIVERSITY
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：
https://reporter.nih.gov/project-details/10548226
关键词：
Acute Adult Anti-Inflammatory Agents Astrocytes Autopsy Basic Science Brain Cells Communication Barriers Cues Data Dendritic Spines Detection Development Device Designs Devices Electric Stimulation Electrodes Electrophysiology (science)Encapsulated Environment Equipment Malfunction Event Excitatory Synapse Exhibits Fluorescent Dyes Gliosis Glutamate Transporter Glutamates Image Immunohistochemistry Implant Implanted Electrodes In Vitro Inflammatory Inflammatory Response Injury Interruption Label Link Measurement Mechanics Mediating Methods Microelectrodes Microglia Microscope Modeling Morphology Motor Cortex N-Methylaspartate Neocortex Nervous System Trauma Neurons Neurotransmitters Noise Outcome Performance Polymers Publishing RNA Interference Radial Rattus Role Scanning Electron Microscopy Shapes Signal Transduction Silicon Slice Source Surface Synapses Synaptic Transmission Synaptic plasticity Testing Thinness Time Time Study Tissues Vertebral column biomaterial compatibility brain tissue cytokine cytotoxicity density electric impedance excitotoxicity functional plasticity gamma-Aminobutyric Acid glial activation implantable device implantation improved in vivo inflammatory marker knock-down microscopic imaging neocortical nervous system disorder neuron loss neuroprosthesis neurotoxicity neurotransmission novel preservation response transmission process two-photon vesicular GABA transporter vesicular 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：
Acta biomaterialia
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.