Abstract
Despite increasing use of in vivo multielectrode array (MEA) implants for basic research and medical applications, the critical structural interfaces formed between the implants and the brain parenchyma, remain elusive. Prevailing view assumes that formation of multicellular inflammatory encapsulating-scar around the implants [the foreign body response (FBR)] degrades the implant electrophysiological functions. Using gold mushroom shaped microelectrodes (gMμEs) based perforated polyimide MEA platforms (PPMPs) that in contrast to standard probes can be thin sectioned along with the interfacing parenchyma; we examined here for the first time the interfaces formed between brains parenchyma and implanted 3D vertical microelectrode platforms at the ultrastructural level. Our study demonstrates remarkable regenerative processes including neuritogenesis, axon myelination, synapse formation and capillaries regrowth in contact and around the implant. In parallel, we document that individual microglia adhere tightly and engulf the gMμEs. Modeling of the formed microglia-electrode junctions suggest that this configuration suffice to account for the low and deteriorating recording qualities of in vivo MEA implants. These observations help define the anticipated hurdles to adapting the advantageous 3D in vitro vertical-electrode technologies to in vivo settings, and suggest that improving the recording qualities and durability of planar or 3D in vivo electrode implants will require developing approaches to eliminate the insulating microglia junctions.
Highlights
Basic and clinically oriented brain research and their applications rely on the use of sophisticated neuroimplants for longterm, simultaneous, multisite extracellular recordings of field potentials (FP) generated by neurons in freely behaving subjects
To address the technical features required to prepare thin sections of implanted gMμE-platforms along with the parenchyma around it, we fabricated non-functional implants constructed of a Perforated Polyimide (PI)-based multielectrode array (MEA) Platform (PPMP) that carries a dense array of gold mushroom shaped microelectrodes
To address the technical features required to prepare thin sections of implanted gMμE platforms along with the parenchyma around it, we fabricated non-functional implants constructed of a Perforated Polyimide (PI)-based MEA Platform (PPMP) that carries a dense array of gold mushroom shaped microelectrodes
Summary
Basic and clinically oriented brain research and their applications rely on the use of sophisticated neuroimplants for longterm, simultaneous, multisite extracellular recordings of field potentials (FP) generated by neurons in freely behaving subjects. Current in vivo brain implants are “blind” to sub-threshold synaptic potentials generated by individual neurons. This implies that critical elements of the brains signaling repertoire and computational components are ignored. Whereas ever-improving spike-detecting, spikesorting and signal averaging techniques make it possible to extract significant information from monitoring extracellular FP (Quiroga et al, 2004; Einevoll et al, 2012; Carlson and Carin, 2019), the limited recording qualities of current multielectrode array-implants (MEA implants) and their deterioration in time considerably hinder the research progress
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