Optometry and Vision Sciences - Research Publications

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    Preferential modulation of individual retinal ganglion cells by electrical stimulation
    Yunzab, M ; Soto-Breceda, A ; Maturana, M ; Kirkby, S ; Slattery, M ; Newgreen, A ; Meffin, H ; Kameneva, T ; Burkitt, AN ; Ibbotson, M ; Tong, W (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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    Activity of Retinal Neurons Can Be Modulated by Tunable Near-Infrared Nanoparticle Sensors.
    Begeng, JM ; Tong, W ; Rosal, BD ; Ibbotson, M ; Kameneva, T ; Stoddart, PR (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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    Analysis of extracellular spike waveforms and associated receptive fields of neurons in cat primary visual cortex
    Sun, SH ; Almasi, A ; Yunzab, M ; Zehra, S ; Hicks, DG ; Kameneva, T ; Ibbotson, MR ; Meffin, H (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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    Adaptive Surround Modulation of MT Neurons: A Computational Model
    Zarei Eskikand, P ; Kameneva, T ; Burkitt, AN ; Grayden, DB ; Ibbotson, MR (FRONTIERS MEDIA SA, 2020-10-26)
    The classical receptive field (CRF) of a spiking visual neuron is defined as the region in the visual field that can generate spikes when stimulated by a visual stimulus. Many visual neurons also have an extra-classical receptive field (ECRF) that surrounds the CRF. The presence of a stimulus in the ECRF does not generate spikes but rather modulates the response to a stimulus in the neuron's CRF. Neurons in the primate Middle Temporal (MT) area, which is a motion specialist region, can have directionally antagonistic or facilitatory surrounds. The surround's effect switches between directionally antagonistic or facilitatory based on the characteristics of the stimulus, with antagonistic effects when there are directional discontinuities but facilitatory effects when there is directional coherence. Here, we present a computational model of neurons in area MT that replicates this observation and uses computational building blocks that correlate with observed cell types in the visual pathways to explain the mechanism of this modulatory effect. The model shows that the categorization of MT neurons based on the effect of their surround depends on the input stimulus rather than being a property of the neurons. Also, in agreement with neurophysiological findings, the ECRFs of the modeled MT neurons alter their center-surround interactions depending on image contrast.