Nanoelectronics enabled chronic multimodal neural platform in a mouse ischemic model

Abstract

Background Despite significant advancements of optical imaging techniques for mapping hemodynamics in small animal models, it remains challenging to combine imaging with spatially resolved electrical recording of individual neurons especially for longitudinal studies. This is largely due to the strong invasiveness to the living brain from the penetrating electrodes and their limited compatibility with longitudinal imaging. New Method We implant arrays of ultraflexible nanoelectronic threads (NETs) in mice for neural recording both at the brain surface and intracortically, which maintain great tissue compatibility chronically. By mounting a cranial window atop of the NET arrays that allows for chronic optical access, we establish a multimodal platform that combines spatially resolved electrical recording of neural activity and laser speckle contrast imaging (LSCI) of cerebral blood flow (CBF) for longitudinal studies. Results We induce peri-infarct depolarizations (PIDs) by targeted photothrombosis, and show the ability to detect its occurrence and propagation through spatiotemporal variations in both extracellular potentials and CBF. We also demonstrate chronic tracking of single-unit neural activity and CBF over days after photothrombosis, from which we observe reperfusion and increased firing rates. Comparison with Existing Method(s) This multimodal platform enables simultaneous mapping of neural activity and hemodynamic parameters at the microscale for quantitative, longitudinal comparisons with minimal perturbation to the baseline neurophysiology. Conclusion The ability to spatiotemporally resolve and chronically track CBF and neural electrical activity in the same living brain region has broad applications for studying the interplay between neural and hemodynamic responses in health and in cerebrovascular and neurological pathologies.

Multimodal mapping of neural activity and cerebral blood flow reveals long-lasting neurovascular dissociations after small-scale strokes

“…We employed a modified cranial window technique and implanted multi-shank NET arrays, which permitted spatially resolving neural activity spanning the depth and lateral locations under the optical window ( Figure 1A-1F, representative recording from 4-shank, Figure S1) (12,13). The experiments started at least four weeks after the cranial surgery, which allowed for the recovery of nearby vasculature from the implantation damage (12,13). We induced targeted photothrombosis and occluded one or a few branches of descending arterioles to induce small-scale, focal ischemia in the sensory cortex of awake mice.…”

“…We took advantage of our recently developed ultraflexible nanoelectronic threads (NETs) (12), which facilitate chronic optical imaging and afford long-lasting, stable recording of unit activities at minimal perturbation to the baseline neurophysiology (12,13). We combined multi-shank, multidepth neural recording with multi-exposure speckle imaging (MESI), a refinement of speckle contrast imaging that enables quantification of CBF for longitudinal and cross-animal comparisons with high resolution at large field of view (14,15).…”

Cortex-wide neural interfacing via transparent polymer skulls

“…In the future, it may be possible to perform random access 2P imaging across the whole FOV using customized long working distance high-resolution objectives, or by using optical relays between the PET surface and the objectives to allow more room for introduction of recording probes 71 . Neural probes that are specifically designed to be compatible with 2P imaging could also be engineered, or flexible neural probes that can be reconfigured after implantation to provide unimpeded optical access could be used 72 .…”

Developing Next-Generation Brain Sensing Technologies—A Review

“…In vivo two-photon [65] imaging and postmortem histological analysis show fully recovered capillaries with an intact blood-brain barrier, absence of chronic neuronal degeneration and glial scar. Future work is underway to scale up these ultra-flexible electrodes to achieve large-scale, high-density and long-term neural recording [70], and combining electrical measurements with optical imaging [71], [72].…”