Optometry and Vision Sciences - Research Publications
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ItemNo Preview AvailablePreferential modulation of individual retinal ganglion cells by electrical stimulation(IOP Publishing Ltd, 2022-08-01)Objective.Retinal prostheses have had limited success in vision restoration through electrical stimulation of surviving retinal ganglion cells (RGCs) in the degenerated retina. This is partly due to non-preferential stimulation of all RGCs near a single stimulating electrode, which include cells that conflict in their response properties and their contribution to visiual processing. Our study proposes a stimulation strategy to preferentially stimulate individual RGCs based on their temporal electrical receptive fields (tERFs).Approach.We recorded the responses of RGCs using whole-cell patch clamping and demonstrated the stimulation strategy, first using intracellular stimulation, then via extracellular stimulation.Main results. We successfully reconstructed the tERFs according to the RGC response to Gaussian white noise current stimulation. The characteristics of the tERFs were extracted and compared based on the morphological and light response types of the cells. By re-delivering stimulation trains that were composed of the tERFs obtained from different cells, we could preferentially stimulate individual RGCs as the cells showed lower activation thresholds to their own tERFs.Significance.This proposed stimulation strategy implemented in the next generation of recording and stimulating retinal prostheses may improve the quality of artificial vision.
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ItemNo Preview AvailableActivity of Retinal Neurons Can Be Modulated by Tunable Near-Infrared Nanoparticle Sensors.(American Chemical Society (ACS), 2023-02-14)The vision of patients rendered blind by photoreceptor degeneration can be partially restored by exogenous stimulation of surviving retinal ganglion cells (RGCs). Whereas conventional electrical stimulation techniques have failed to produce naturalistic visual percepts, nanoparticle-based optical sensors have recently received increasing attention as a means to artificially stimulate the RGCs. In particular, nanoparticle-enhanced infrared neural modulation (NINM) is a plasmonically mediated photothermal neuromodulation technique that has a demonstrated capacity for both stimulation and inhibition, which is essential for the differential modulation of ON-type and OFF-type RGCs. Gold nanorods provide tunable absorption through the near-infrared wavelength window, which reduces interference with any residual vision. Therefore, NINM may be uniquely well-suited to retinal prosthesis applications but, to our knowledge, has not previously been demonstrated in RGCs. In the present study, NINM laser pulses of 100 μs, 500 μs and 200 ms were applied to RGCs in explanted rat retinae, with single-cell responses recorded via patch-clamping. The shorter laser pulses evoked robust RGC stimulation by capacitive current generation, while the long laser pulses are capable of inhibiting spontaneous action potentials by thermal block. Importantly, an implicit bias toward OFF-type inhibition is observed, which may have important implications for the feasibility of future high-acuity retinal prosthesis design based on nanoparticle sensors.
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ItemOrientation pinwheels in primary visual cortex of a highly visual marsupial(AMER ASSOC ADVANCEMENT SCIENCE, 2022-09-30)Primary visual cortices in many mammalian species exhibit modular and periodic orientation preference maps arranged in pinwheel-like layouts. The role of inherited traits as opposed to environmental influences in determining this organization remains unclear. Here, we characterize the cortical organization of an Australian marsupial, revealing pinwheel organization resembling that of eutherian carnivores and primates but distinctly different from the simpler salt-and-pepper arrangement of eutherian rodents and rabbits. The divergence of marsupials from eutherians 160 million years ago and the later emergence of rodents and rabbits suggest that the salt-and-pepper structure is not the primitive ancestral form. Rather, the genetic code that enables complex pinwheel formation is likely widespread, perhaps extending back to the common therian ancestors of modern mammals.
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ItemNo Preview AvailableEnhanced effective diffusion in sub-wavelength, axon-scale microchannels using surface acoustic waves(AIP Publishing, 2023-03)Excitation using surface acoustic waves (SAW) has demonstrated efficacy in improving microscale particle/chemical transport due to its ability to generate microscale wavelengths. However, the effects of acoustic stimulation on transport processes along the length of sub-wavelength microchannels and their underlying mechanisms, essential for long-range transport, have not been examined in detail. In this work, we investigate diffusion along the length of subwavelength microchannels using experimental and simulation approaches, demonstrating enhanced transport under SAW excitation. The microchannel-based enhanced diffusion mechanisms are further studied by investigating the acoustic pressure and streaming fields, finding that the degree of enhancement is a function of applied power, microchannel dimensions, and viscosity. This microchannel-based diffusion enhancement approach is applicable to microfluidic and biomedical microscale transport enhancement, with the findings here being relevant to acoustic-based micro-mixing and neurodegenerative therapies.
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ItemAnalysis of extracellular spike waveforms and associated receptive fields of neurons in cat primary visual cortex(WILEY, 2021-04)KEY POINTS: Extracellular spikes recorded in the visual cortex (Area 17/18, V1) are commonly classified into either regular-spiking (RS) or fast-spiking (FS). Using multi-electrode arrays positioned in cat V1 and a broadband stimulus, we show that there is also a distinct class with positive-spiking (PS) waveforms. PS units were associated mainly with non-oriented receptive fields while RS and FS units had orientation-selective receptive fields. We suggest that PS units are recordings of axons originating from the thalamus. This conclusion was reinforced by our finding that we could record PS units after cortical silencing, but not record RS and FS units. The importance of our findings is that we were able to correlate spike shapes with receptive field characteristics with high precision using multi-electrode extracellular recording techniques. This allows considerable increases in the amount of information that can be extracted from future cortical experiments. ABSTRACT: Extracellular spike waveforms from recordings in the visual cortex have been classified into either regular-spiking (RS) or fast-spiking (FS) units. While both these types of spike waveforms are negative-dominant, we show that there are also distinct classes of spike waveforms in visual Area 17/18 (V1) of anaesthetised cats with positive-dominant waveforms, which are not regularly reported. The spatial receptive fields (RFs) of these different spike waveform types were estimated, which objectively revealed the existence of oriented and non-oriented RFs. We found that units with positive-dominant spikes, which have been associated with recordings from axons in the literature, had mostly non-oriented RFs (84%), which are similar to the centre-surround RFs observed in the dorsal lateral geniculate nucleus (dLGN). Thus, we hypothesise that these positive-dominant waveforms may be recordings from dLGN afferents. We recorded from V1 before and after the application of muscimol (a cortical silencer) and found that the positive-dominant spikes (PS) remained while the RS and FS cells did not. We also noted that the PS units had spiking characteristics normally associated with dLGN units (i.e. higher response spike rates, lower response latencies and higher proportion of burst spikes). Our findings show quantitatively that it is possible to correlate the RF properties of cortical neurons with particular spike waveforms. This has implications for how extracellular recordings should be interpreted and complex experiments can now be contemplated that would have been very challenging previously, such as assessing the feedforward connectivity between brain areas in the same location of cortical tissue.
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ItemAdvances in Carbon-Based Microfiber Electrodes for Neural Interfacing(FRONTIERS MEDIA SA, 2021-04-12)Neural interfacing devices using penetrating microelectrode arrays have emerged as an important tool in both neuroscience research and medical applications. These implantable microelectrode arrays enable communication between man-made devices and the nervous system by detecting and/or evoking neuronal activities. Recent years have seen rapid development of electrodes fabricated using flexible, ultrathin carbon-based microfibers. Compared to electrodes fabricated using rigid materials and larger cross-sections, these microfiber electrodes have been shown to reduce foreign body responses after implantation, with improved signal-to-noise ratio for neural recording and enhanced resolution for neural stimulation. Here, we review recent progress of carbon-based microfiber electrodes in terms of material composition and fabrication technology. The remaining challenges and future directions for development of these arrays will also be discussed. Overall, these microfiber electrodes are expected to improve the longevity and reliability of neural interfacing devices.
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ItemHigh Fidelity Bidirectional Neural Interfacing with Carbon Fiber Microelectrodes Coated with Boron-Doped Carbon Nanowalls: An Acute Study(WILEY-V C H VERLAG GMBH, 2020-12)Abstract Implantable electrodes that can communicate with a small, selective group of neurons via both neural stimulation and recording are critical for the development of advanced neuroprosthetic devices. Microfiber electrodes with neuron‐scale cross‐sections have the potential to improve the spatial resolution for both stimulation and recording, while minimizing the chronic inflammation response after implantation. In this work, glass insulated microfiber electrodes are fabricated by coating carbon fibers with boron‐doped carbon nanowalls. The coating significantly improves the electrochemical properties of carbon fibers, leading to a charge injection capacity of 7.82 ± 0.35 mC cm−2, while retaining good flexibility, stability and biocompatibility. When used for neural interfacing, the coated microelectrodes successfully elicit localized stimulation responses in explanted retina, and are also able to detect signals from single neurons, in vivo with a signal‐to‐noise ratio as high as 6.7 in an acute study. This is the first report of using carbon nanowall coated carbon fibers for neural interfacing.
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ItemMechanisms and Applications of Neuromodulation Using Surface Acoustic Waves-A Mini-Review(FRONTIERS MEDIA SA, 2021-01-27)The study of neurons is fundamental for basic neuroscience research and treatment of neurological disorders. In recent years ultrasound has been increasingly recognized as a viable method to stimulate neurons. However, traditional ultrasound transducers are limited in the scope of their application by self-heating effects, limited frequency range and cavitation effects during neuromodulation. In contrast, surface acoustic wave (SAW) devices, which are producing wavemodes with increasing application in biomedical devices, generate less self-heating, are smaller and create less cavitation. SAW devices thus have the potential to address some of the drawbacks of traditional ultrasound transducers and could be implemented as miniaturized wearable or implantable devices. In this mini review, we discuss the potential mechanisms of SAW-based neuromodulation, including mechanical displacement, electromagnetic fields, thermal effects, and acoustic streaming. We also review the application of SAW actuation for neuronal stimulation, including growth and neuromodulation. Finally, we propose future directions for SAW-based neuromodulation.
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ItemOcellar structure and neural innervation in the honeybee(FRONTIERS MEDIA SA, 2014-02-19)Honeybees have a visual system composed of three ocelli (simple eyes) located on the top of the head, in addition to two large compound eyes. Although experiments have been conducted to investigate the role of the ocelli within the visual system, their optical characteristics, and function remain controversial. In this study, we created three-dimensional (3-D) reconstructions of the honeybee ocelli, conducted optical measurements and filled ocellar descending neurons to assist in determining the role of ocelli in honeybees. In both the median and lateral ocelli, the ocellar retinas can be divided into dorsal and ventral parts. Using the 3-D model we were able to assess the viewing angles of the retinas. The dorsal retinas view the horizon while the ventral retinas view the sky, suggesting quite different roles in attitude control. We used the hanging drop technique to assess the spatial resolution of the retinas. The lateral ocelli have significantly higher spatial resolution compared to the median ocellus. In addition, we established which ocellar retinas provide the input to five pairs of large ocellar descending neurons. We found that four of the neuron pairs have their dendritic fields in the dorsal retinas of the lateral ocelli, while the fifth has fine dendrites in the ventral retina. One of the neuron pairs also sends very fine dendrites into the border region between the dorsal and ventral retinas of the median ocellus.
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ItemOptical stimulation of neural tissue(INST ENGINEERING TECHNOLOGY-IET, 2020-06)Electrical stimulation has been used for decades in devices such as pacemakers, cochlear implants and more recently for deep brain and retinal stimulation and electroceutical treatment of disease. However, current spread from the electrodes limits the precision of neural activation, leading to a low quality therapeutic outcome or undesired side-effects. Alternative methods of neural stimulation such as optical stimulation offer the potential to deliver higher spatial resolution of neural activation. Direct optical stimulation is possible with infrared light, while visible light can be used to activate neurons if the neural tissue is genetically modified with a light sensitive ion channel. Experimentally, both methods have resulted in highly precise stimulation with little spread of activation at least in the cochlea, each with advantages and disadvantages. Infrared neural stimulation does not require modification of the neural tissue, but has very high power requirements. Optogenetics can achieve precision of activation with lower power, but only in conjunction with targeted insertion of a light sensitive ion channel into the nervous system via gene therapy. This review will examine the advantages and limitations of optical stimulation of neural tissue, using the cochlea as an exemplary model and recent developments for retinal and deep brain stimulation.