Post-explant profiling of subcellular-scale carbon fiber intracortical electrodes and surrounding neurons enables modeling of recorded electrophysiology

Abstract

Objective. Characterizing the relationship between neuron spiking and the signals that electrodes record is vital to defining the neural circuits driving brain function and informing clinical brain-machine interface design. However, high electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship. Approach. Here, we demonstrate consistent localization of the recording site tips of subcellular-scale (6.8 µm diameter) carbon fiber electrodes and the positions of surrounding neurons. We implanted male rats with carbon fiber electrode arrays for 6 or 12 weeks targeting layer V motor cortex. After explanting the arrays, we immunostained the implant site and localized putative recording site tips with subcellular-cellular resolution. We then 3D segmented neuron somata within a 50 µm radius from implanted tips to measure neuron positions and health and compare to healthy cortex with symmetric stereotaxic coordinates. Main results. Immunostaining of astrocyte, microglia, and neuron markers confirmed that overall tissue health was indicative of high biocompatibility near the tips. While neurons near implanted carbon fibers were stretched, their number and distribution were similar to hypothetical fibers placed in healthy contralateral brain. Such similar neuron distributions suggest that these minimally invasive electrodes demonstrate the potential to sample naturalistic neural populations. This motivated the prediction of spikes produced by nearby neurons using a simple point source model fit using recorded electrophysiology and the mean positions of the nearest neurons observed in histology. Comparing spike amplitudes suggests that the radius at which single units can be distinguished from others is near the fourth closest neuron (30.7±4.6 µm, X̄±S) in layer V motor cortex. Significance. Collectively, these data and simulations provide the first direct evidence that neuron placement in the immediate vicinity of the recording site influences how many spike clusters can be reliably identified by spike sorting.

Planar amorphous silicon carbide microelectrode arrays for chronic recording in rat motor cortex

“…Neuronal cell bodies, confirmed by immunohistochemistry four weeks after implantation, were also observed adjacent to the 20 µm 2 structures [26]. Subcellular scale carbon fiber microwires have also been shown to have reduced FBR when examining implantation sites after 12 weeks in vivo [27]. Intrinsically stiff, but highly flexible carbon fiber electrodes with cross sectional areas of 60 µm 2 were shown to reduce gliosis when compared to commercially available electrode arrays [28].…”

Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior

“…Implanted electrodes typically record action potentials from immediately nearby neurons (<~50 μm). 61 Even small displacements between the recording contacts and the cells lead to waveform changes 62 or signal loss. Furthermore, delicate nervous tissues are sensitive to micromotion-induced injuries.…”

Artifact-Minimized High-Ratio Image Compression with Preserved Analysis Fidelity

“…Our benchmark dataset is composed of 5 image samples from different microscopy modalities, including low contrast point scanning confocal microscopy images of NeuN staining 28 , high contrast point scanning confocal images of Brainbow-labeled mouse neurons 29 (Brainbow), expansion line scanning confocal microscopy images of DRAQ5 stained mouse brain nuclei (DRAQ5), STochastic Optical Reconstruction Microscopy (STORM) images of β 2-spectrin labeling in cultured hippocampal neurons 30 , and Electron microscope (EM) scanned Drosophila melanogaster larval neuropil 31 (Fig. 2, Supplementary Fig.…”