Abstract
.Significance: Electrophysiological recording and optical imaging are two prevalent neurotechnologies with complementary strengths, the combined application of which can significantly improve our capacity in deciphering neural circuits. Flexible electrode arrays can support longitudinal optical imaging in the same brain region, but their mechanical flexibility makes surgical preparation challenging. Here, we provide a step-by-step protocol by which an ultraflexible nanoelectronic thread is co-implanted with a cranial window in a single surgery to enable chronic, dual-modal measurements.Aim: The method uses -thick polymer neural electrodes which conform to the site of implantation. The mechanical flexibility of the probe allows bending without breaking and enables long-lasting electrophysiological recordings of single-unit activities and concurrent, high-resolution optical imaging through the cranial window.Approach: The protocol describes methods and procedures to co-implant an ultraflexible electrode array and a glass cranial window in the mouse neocortex. The implantation strategy includes temporary attachment of flexible electrodes to a retractable tungsten-microwire insertion shuttle, craniotomy, stereotaxic insertion of the electrode array, skull fixation of the cranial window and electrode, and installation of a head plate.Results: The resultant implant allows simultaneous interrogation of brain activity both electrophysiologically and optically for several months. Importantly, a variety of optical imaging modalities, including wide-field fluorescent imaging, two-photon microscopy, and functional optical imaging, can be readily applied to the specific brain region where ultraflexible electrodes record from.Conclusions: The protocol describes a method for co-implantation of ultraflexible neural electrodes and a cranial window for chronic, multimodal measurements of brain activity in mice. Device preparation and surgical implantation are described in detail to guide the adaptation of these methods for other flexible neural implants and cranial windows.
Highlights
The brain has an enormous dynamic range spatially and temporally
The protocol describes a method for co-implantation of ultraflexible neural electrodes and a cranial window for chronic, multimodal measurements of brain activity in mice
Device preparation and surgical implantation are described in detail to guide the adaptation of these methods for other flexible neural implants and cranial windows
Summary
The brain has an enormous dynamic range spatially and temporally. Noble et al.: Chronic co-implantation of ultraflexible neural electrodes and a cranial window adaptation, learning, development, and degeneration occur on broader timescales ranging from seconds to years and even decades.[2,3,4] Spatially, neural activity involves cellular and subcellular structural and functional changes, and orchestrated activities distributed across multiple brain areas. Optical imaging and modulation techniques offer high spatial resolution[8,9] and cell type specificity,[10] and can measure non-neuronal, non-electrical activities.[11,12] they are limited by their generally low temporal resolution and insufficient tissue penetration depth. Integrating the electrical and optical measurements in the same brain leverages their complementary strengths, which has become an emerging approach for synchronously observing and controlling brain activities of a specific region.[13,14,15,16,17,18]
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