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一种高灵敏度的纳米修饰生物传感器,用于动态监测来自大鼠皮层到海马亚区的谷氨酸和神经尖峰的共变。

A high-sensitive nano-modified biosensor for dynamic monitoring of glutamate and neural spike covariation from rat cortex to hippocampal sub-regions.

机构信息

State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 10090, China.

State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 10090, China.

出版信息

J Neurosci Methods. 2017 Nov 1;291:122-130. doi: 10.1016/j.jneumeth.2017.08.015. Epub 2017 Aug 19.

DOI:10.1016/j.jneumeth.2017.08.015
PMID:28830725
Abstract

BACKGROUND

Hippocampus is a critical part of brain tissue involved in many cognitive neural activities. They are controlled by various neurotransmitters such as glutamate (Glu), and affected by electrophysiology.

NEW METHOD

Herein, we fabricated a 16-site (25μm in diameter) microelectrode array (MEA) biosensor applied in dual-mode tests including Glu and neural spike measurements.

METHODS

All the 16 recording sites were electrodeposited with platinum nanoparticles (PtNPs) and 8 sites were used for electrical recording. Glutamate oxidase enzyme (Gluox) and 1,3-Phenylenediamine (mPD) layer were specially modified on the other 8 sites for Glu recording. The dual-mode MEA was implanted from cortex to hippocampus of anesthetized rat to record Glu content and firing rate.

RESULTS

The electrical sites showed much lower impedance. The Glu sites showed much higher sensitivity(7.807 pA/μM), and ideal selectivity to the major molecules in brain. The post calibration sensitivity (3.935 pA/μM) maintained on a positive level. Different Glu content peaks including cortex (18.32μM) and hippocampal CA1 (4.39μM), CA3 (10.16μM), dentate gyrus (DG, two layers: 5.36μM and 10.34μM) have detected. The corresponded firing rate was recorded, too.

COMPARISON WITH EXISTING METHODS

This modification showed much lower impedance and much higher sensitivity. We obtained more neuron activities simultaneously by dual-mode recording. The covariation of Glu and neural spike signals was discovered in the specific hippocampus sub-region.

CONCLUSIONS

The covariation between Glu and firing rate changes were synchronous, and effected by regions. The dual-mode signals were useful to find the neurology disease mechanism.

摘要

背景

海马体是大脑组织的重要组成部分,参与多种认知神经活动。它们受各种神经递质如谷氨酸(Glu)的控制,并受电生理学影响。

新方法

在此,我们制作了一个 16 位(直径 25μm)微电极阵列(MEA)生物传感器,应用于包括 Glu 和神经尖峰测量在内的双模式测试。

方法

所有 16 个记录位点都沉积了铂纳米粒子(PtNPs),其中 8 个位点用于电记录。谷氨酸氧化酶(Gluox)和 1,3-苯二胺(mPD)层特别修饰在其他 8 个用于 Glu 记录的位点上。双模式 MEA 从麻醉大鼠的皮层植入到海马体,以记录 Glu 含量和放电率。

结果

电记录位点的阻抗明显较低。Glu 记录位点对大脑中的主要分子表现出更高的灵敏度(7.807 pA/μM)和理想的选择性。经后校准的灵敏度(3.935 pA/μM)保持在较高水平。检测到不同的 Glu 含量峰,包括皮层(18.32μM)和海马体 CA1(4.39μM)、CA3(10.16μM)、齿状回(DG,两层:5.36μM 和 10.34μM)。同时记录到相应的放电率。

与现有方法的比较

这种修饰方法显示出更低的阻抗和更高的灵敏度。我们通过双模式记录同时获得了更多的神经元活动。在特定的海马体亚区发现了 Glu 和神经尖峰信号的变化之间的相关性。

结论

Glu 和放电率变化之间的相关性是同步的,并受区域影响。双模式信号有助于发现神经疾病的发病机制。

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