Abstract
The goal for this research was to identify molecular mechanisms that explain animal-to-animal variability in chronic intracortical recordings. Microwire electrodes were implanted into Sprague Dawley rats at an acute (1 week) and a chronic (14 weeks) time point. Weekly recordings were conducted, and action potentials were evoked in the barrel cortex by deflecting the rat's whiskers. At 1 and 14 weeks, tissue was collected, and mRNA was extracted. mRNA expression was compared between 1 and 14 weeks using a high throughput multiplexed qRT-PCR. Pearson correlation coefficients were calculated between mRNA expression and signal-to-noise ratios at 14 weeks. At 14 weeks, a positive correlation between signal-to-noise ratio (SNR) and NeuN and GFAP mRNA expression was observed, indicating a relationship between recording strength and neuronal population, as well as reactive astrocyte activity. The inflammatory state around the electrode interface was evaluated using M1-like and M2-like markers. Expression for both M1-like and M2-like mRNA markers remained steady from 1 to 14 weeks. Anti-inflammatory markers, CD206 and CD163, however, demonstrated a significant positive correlation with SNR quality at 14 weeks. VE-cadherin, a marker for adherens junctions, and PDGFR-β, a marker for pericytes, both partial representatives of blood-brain barrier health, had a positive correlation with SNR at 14 weeks. Endothelial adhesion markers revealed a significant increase in expression at 14 weeks, while CD45, a pan-leukocyte marker, significantly decreased at 14 weeks. No significant correlation was found for either the endothelial adhesion or pan-leukocyte markers. A positive correlation between anti-inflammatory and blood-brain barrier health mRNA markers with electrophysiological efficacy of implanted intracortical electrodes has been demonstrated. These data reveal potential mechanisms for further evaluation to determine potential target mechanisms to improve consistency of intracortical electrodes recordings and reduce animal-to-animal/implant-to-implant variability.
Highlights
Previous work has suggested that the severity and duration of chronic blood–brain barrier (BBB) breach may influence chronic recordings (Potter et al, 2012; Saxena et al, 2013; Nolta et al, 2015; Kozai et al, 2016)
The results have shown a negative correlation between IgG localization at the electrode interface and signal-to-noise ratio (SNR) (Karumbaiah et al, 2013; Saxena et al, 2013; Nolta et al, 2015)
Pearson correlation coefficients and p-values were calculated for each mRNA primer and the corresponding animal’s SNR
Summary
Brain machine interfaces (BMIs) using intracortical electrodes are promising to restore virtual and physical functionality to paralysis patients (Simeral et al, 2011; Collinger et al, 2013; Perge et al, 2014; Bouton et al, 2016; Downey et al, 2016; Ajiboye et al, 2017). Reduction in amplitude and number of recorded spikes directly impacts the accuracy of machine control (Perge et al, 2014) Signal loss in both clinical (Simeral et al, 2011; Collinger et al, 2013; Perge et al, 2014; Bouton et al, 2016; Downey et al, 2016; Ajiboye et al, 2017) and preclinical (Karumbaiah et al, 2013; Saxena et al, 2013; Kozai et al, 2015; Nolta et al, 2015; Sharma et al, 2015; McCreery et al, 2016) intracortical electrode models have been well documented. We investigate the molecular sequelae to implanted intracortical electrodes in the context of SNR to identify possible contributors to recording success
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