PPy/SWCNTs-Modified Microelectrode Array for Learning and Memory Model Construction through Electrical Stimulation and Detection of In Vitro Hippocampal Neuronal Network

Abstract

The learning and memory functions of the brain remain unclear, which are in urgent need for the detection of both a single cell signal with high spatiotemporal resolution and network activities with high throughput. Here, an in vitro microelectrode array (MEA) was fabricated and further modified with polypyrrole/carboxylated single-walled carbon nanotubes (PPy/SWCNTs) nanocomposites as the interface between biological and electronic systems. The deposition of the nanocomposites significantly improved the performance of microelectrodes including low impedance (60.3 ± 28.8 k Ω), small phase delay (−32.8 ± 4.4°), and good biocompatibility. Then the modified MEA was used to apply learning training and test on hippocampal neuronal network cultured for 21 days through electrical stimulation, and multichannel electrophysiological signals were recorded simultaneously. During the process of learning training, the stimulus/response ratio of the hippocampal learning population gradually increased and the response time gradually decreased. After training, the mean spikes in burst, number of bursts, and mean burst duration increased by 53%, 191%, and 52%, respectively, and the correlation of neurons in the network was significantly enhanced from 0.45 ± 0.002 to 0.78 ± 0.002. In addition, the neuronal network basically retained these characteristics for at least 5 h. These results indicated that we have successfully constructed a learning and memory model of hippocampal neurons on the in vitro MEA, contributing to understanding learning and memory based on synaptic plasticity. The proposed PPy/SWCNTs-modified in vitro MEA will provide a promising platform for the exploration of learning and memory mechanism and their applications in vitro.

Flexible high-density microelectrode arrays for closed-loop brain–machine interfaces: a review

“…(B) PPy/SWCNTs-modification on microelectrodes for electrical stimulation and detection. Reprinted with permission from Yang et al (2023) . Copyright 2023 American Chemical Society.…”

“…The application of CNTs significantly increases the surface area, thereby increasing the charge storage capacity and the injection limit, with other benefits such as good adhesion, non-toxicity, and stable properties ( Fattahi et al, 2014 ; Barai et al, 2018 ). Yang et al (2023) used polypyrrole/carboxylated single-walled carbon nanotubes (PPy/SWCNTs) nanocomposites for electrode modification. The nanocomposites not only improved the performance of microelectrodes with low impedance (60.3 ± 28.8 kappa O) and small phase delay (−32.8 ± 4.4 degrees), but also presented stability for in vivo stimulation and recording for 21 days, as shown in Figure 3B .…”

“…The shape and spatial configuration of HDMEAs are crucial for neural interfacing, with designs ranging from flat, planar structures to complex, curved (Ji et al, 2020a), or three-dimensional (3D) forms (Le Floch et al, 2022;Brown et al, 2023;McDonald et al, 2023) tailored to specific anatomical contexts, such as the cortical surface or deep brain regions. The overall shape impacts the HDMEA's ability to establish a stable interface with neural tissues, its mechanical stability, and its long-term biocompatibility, while the arrangement of electrodes-potentially organized in grids (Park et al, 2018; Figure 1B), linear arrays (Musk, 2019;Yang et al, 2023) (Figures 2A, 3B), fiber shape (Park et al, 2021; Figure 2D) or intricate patterns (Uguz and Shepard, 2022;Zhou et al, 2023; Figures 2B,C, 4A)-and their individual shapes and sizes are meticulously crafted to enhance signal acquisition and stimulation capabilities.…”

Using Human‐Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review

“…The typical planar MEA fabrication processes employ Micro‐Electro‐Mechanical System (MEMS) technology, and the fabrication steps include cleaning, photolithography, sputtering, stripping, deposition and etching, [ 88–90 ] as shown in Figure . Traditional in vitro planar electrodes utilize a glass substrate, while silicon‐based electrodes, commonly used for in vivo applications, can also be employed for implantable detection of 3D organoids.…”