Brain responses to micro-machined silicon devices

Szarowski, Donald H.; Andersen, Maja Dam; Retterer, Scott T.; Spence, Andrew J.; Isaacson, M.; Craighead, Harold G.; Turner, James N.; Shain, William

doi:10.1016/s0006-8993(03)03023-3

Cited by 746 publications

(843 citation statements)

References 43 publications

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“…We are able to release 0.5 µg/cm 2 Dex after each CV cycle and to a total of nearly 16 µg/cm 2 after 30 CV cycles. Based on most of the histological studies, the reactive region indicated by enhanced glial fibrillary acidic protein (GFAP), a key intermediate filament, activity around the neural electrode arrays has a radius of less than 500 µm [7,48]. A release of 0.5 µg/cm 2 Dex will result in average Dex concentration of 1 µM within 500 µm radius from the electrode.…”

Section: Resultsmentioning

confidence: 99%

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Wadhwa

Lagenaur

Cui

2006

Journal of Controlled Release

459

393

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Chronic recordings from micromachined neural electrode arrays often fail a few weeks after implantation primarily due to the formation of an astro-glial sheath around the implant. We propose a drug delivery system, from conducting polymer (CP) coatings on the electrode sites, to modulate the inflammatory implant-host tissue reaction. In this study, polypyrrole (PPy) based coatings for electrically controlled and local delivery of the ionic form of an anti-inflammatory drug, dexamethasone (Dex), was investigated. The drug was incorporated in PPy via electropolymerization of pyrrole and released in PBS using cyclic voltammetry (CV). FTIR analysis of the surface showed the presence of Dex and polypyrrole on the coated electrode. The thickness of the coated film was estimated to be ~50 nm by ellipsometry. We were able to release 0.5 µg/cm 2 Dex in 1 CV cycle and upto 92% Dex after 30 CV cycles. In-vitro studies and immunocytochemistry on murine glial cells suggest that the released drug lowers the count of reactive astrocytes to the same extent as the added drug. In addition, the released drug is not toxic to neurons as seen by healthy neuronal viability in the released drug treated cells.

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Section: Resultsmentioning

confidence: 99%

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Wadhwa

Lagenaur

Cui

2006

Journal of Controlled Release

459

393

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“…Previous attempts to address one of these concerns have come at the expense of the other. Bundles of fibers illuminate larger volumes, but the increased penetration diameter leads to greater tissue and vascular damage, because the damage is proportional to fiber diameter (19,(44)(45)(46)(47)(48). Tapered glass fibers reduce penetration damage, but narrowly focus light to tiny illumination areas (<100 μm 2 ) (13,49).…”

Section: Significancementioning

confidence: 99%

FEF inactivation with improved optogenetic methods

Acker

Pino

Boyden

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

114

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Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light-shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm 3 of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities (≤100 mW/mm 2 ) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods).primate | optogenetics | FEF | Jaws | memory-guided saccade T he frontal eye field (FEF) is an important brain area for making saccades to remembered locations. FEF neurons increase their firing rate during three epochs of memory-guided saccades: (i) target presentation, (ii) delay period, and (iii) motor preparation. Pharmacological inactivation of the FEF impairs memory-guided saccades (1-7), but because pharmacological inactivation inhibits all FEF neuronal activity, it is unclear if the FEF's role is specific to one or more task epochs (8,9). By selectively inactivating the FEF during each task epoch, we can determine whether visual-, delay-, or motor-related firing (or some combination of the three types of firing) contributes to memory-guided saccades.The ideal tool for this study is optogenetics, which allows for millisecond-precise, light-driven neuronal control. Unfortunately, although optogenetics is widely used to study functional physiology and disease models in rodents and invertebrates, technical challenges have limited the use of optogenetics in the nonhuman primate brain, which has a volume ∼100-fold larger than the rodent brain (10). Pioneering studies in monkeys reported small behavioral effects with excitatory (11-14) and inhibitory opsins (15-17). These studies used large light power densities (several hundreds of milliwatts per square meter to 20 W/mm 2 ) but illuminated only small volumes, at most 1 mm 3 , due to both the chosen wavelength and light-deliver...

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“…At a cellular level, it has been shown that activated, proliferating microglia appear around the implant site as early as 1-day post implantation [18,21,42]. These activated microglia are thought to gradually diminish both excess fluid and cellular debris 6 -8 days after the implant, although necrotic tissue has been observed up to 42 days later [41,44].…”

Section: Introductionmentioning

confidence: 99%

“…These activated microglia are thought to gradually diminish both excess fluid and cellular debris 6 -8 days after the implant, although necrotic tissue has been observed up to 42 days later [41,44]. At later time points, typical inflammatory cells or hemorrhaging has not been observed [47], while others have documented neuronal cell loss and macrophages up to 112 days after the implant [6,41,42,44]. As a testament to the transitory nature of this mechanically induced wound healing response, electrode tracks could not be found in animals after several months when the electrode was inserted and quickly removed [6,13,35,47].…”

Section: Introductionmentioning

confidence: 99%

Metabolic and behavioral deficits following a routine surgical procedure in rats

et al. 2007

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To test the hypothesis that functional metabolic deficits observed following surgical brain injury are associated with changes in cognitive performance in rodents, we performed serial imaging studies in parallel with behavioral measures in control animals and in animals with surgical implants. Memory function was assessed using the novel object recognition (NOR) test, administered 3 days prior to and 3, 7, 14, and 56 days after surgery. At each time point, general locomotion was also measured. Metabolic imaging with 18 F-fluorodeoxyglucose ([ 18 F]FDG) occurred 28 and 58 days after surgery. Animals with surgical implants performed significantly worse on tests of object recognition, while general locomotion was unaffected by the implant. There was a significant decrease in glucose uptake after surgery in most of the hemisphere ipsilateral to the implant relative to the contralateral hemisphere. At both time points, the most significant metabolic deficits occurred in the primary motor cortex (-25%; p<0.001), sensory cortex (-15%, p<0.001) and frontal cortex (-12%; p<0.001). Ipsilateral areas further from the site of insertion became progressively worse, including the sensory cortex, dorsal striatum and thalamus. This data was supported by a voxel-based analysis of the PET data, which revealed again a unilateral decrease in [ 18 F]FDG uptake that extended throughout the ipsilateral cortex and persisted for the duration of the 58-day study. Probe implantation in the striatum results in a widespread and long lasting decline in cortical glucose metabolism together with a persistent, injury-related deficit in the performance of a cognitive (object recognition) task in rats.

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Brain responses to micro-machined silicon devices

Cited by 746 publications

References 43 publications

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

FEF inactivation with improved optogenetic methods

Metabolic and behavioral deficits following a routine surgical procedure in rats

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