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      Next-generation probes, particles, and proteins for neural interfacing

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          Abstract

          Bidirectional interfacing with the nervous system enables neuroscience research, diagnosis, and therapy. This two-way communication allows us to monitor the state of the brain and its composite networks and cells as well as to influence them to treat disease or repair/restore sensory or motor function. To provide the most stable and effective interface, the tools of the trade must bridge the soft, ion-rich, and evolving nature of neural tissue with the largely rigid, static realm of microelectronics and medical instruments that allow for readout, analysis, and/or control. In this Review, we describe how the understanding of neural signaling and material-tissue interactions has fueled the expansion of the available tool set. New probe architectures and materials, nanoparticles, dyes, and designer genetically encoded proteins push the limits of recording and stimulation lifetime, localization, and specificity, blurring the boundary between living tissue and engineered tools. Understanding these approaches, their modality, and the role of cross-disciplinary development will support new neurotherapies and prostheses and provide neuroscientists and neurologists with unprecedented access to the brain.

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          Most cited references208

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          Neocortical excitation/inhibition balance in information processing and social dysfunction.

          Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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            Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin.

            Important Ca2+ signals in the cytosol and organelles are often extremely localized and hard to measure. To overcome this problem we have constructed new fluorescent indicators for Ca2+ that are genetically encoded without cofactors and are targetable to specific intracellular locations. We have dubbed these fluorescent indicators 'cameleons'. They consist of tandem fusions of a blue- or cyan-emitting mutant of the green fluorescent protein (GFP), calmodulin, the calmodulin-binding peptide M13, and an enhanced green- or yellow-emitting GFP. Binding of Ca2+ makes calmodulin wrap around the M13 domain, increasing the fluorescence resonance energy transfer (FRET) between the flanking GFPs. Calmodulin mutations can tune the Ca2+ affinities to measure free Ca2+ concentrations in the range 10(-8) to 10(-2) M. We have visualized free Ca2+ dynamics in the cytosol, nucleus and endoplasmic reticulum of single HeLa cells transfected with complementary DNAs encoding chimaeras bearing appropriate localization signals. Ca2+ concentration in the endoplasmic reticulum of individual cells ranged from 60 to 400 microM at rest, and 1 to 50 microM after Ca2+ mobilization. FRET is also an indicator of the reversible intermolecular association of cyan-GFP-labelled calmodulin with yellow-GFP-labelled M13. Thus FRET between GFP mutants can monitor localized Ca2+ signals and protein heterodimerization in individual live cells.
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              Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics.

              Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.
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                Author and article information

                Journal
                Science Advances
                Sci. Adv.
                American Association for the Advancement of Science (AAAS)
                2375-2548
                June 07 2017
                June 09 2017
                : 3
                : 6
                : e1601649
                Article
                10.1126/sciadv.1601649
                e6859e66-7ba4-44ae-885f-29c538b4c8b6
                © 2017
                History

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