Optometry and Vision Sciences - Research Publications

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    Orientation pinwheels in primary visual cortex of a highly visual marsupial
    Jung, YJ ; Almasi, A ; Sun, SH ; Yunzab, M ; Cloherty, SL ; Bauquier, SH ; Renfree, M ; Meffin, H ; Ibbotson, MR (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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    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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    Mechanisms of Feature Selectivity and Invariance in Primary Visual Cortex.
    Almasi, A ; Meffin, H ; Cloherty, SL ; Wong, Y ; Yunzab, M ; Ibbotson, MR (Oxford University Press (OUP), 2020-09)
    Visual object identification requires both selectivity for specific visual features that are important to the object's identity and invariance to feature manipulations. For example, a hand can be shifted in position, rotated, or contracted but still be recognized as a hand. How are the competing requirements of selectivity and invariance built into the early stages of visual processing? Typically, cells in the primary visual cortex are classified as either simple or complex. They both show selectivity for edge-orientation but complex cells develop invariance to edge position within the receptive field (spatial phase). Using a data-driven model that extracts the spatial structures and nonlinearities associated with neuronal computation, we quantitatively describe the balance between selectivity and invariance in complex cells. Phase invariance is frequently partial, while invariance to orientation and spatial frequency are more extensive than expected. The invariance arises due to two independent factors: (1) the structure and number of filters and (2) the form of nonlinearities that act upon the filter outputs. Both vary more than previously considered, so primary visual cortex forms an elaborate set of generic feature sensitivities, providing the foundation for more sophisticated object processing.
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    Hybrid diamond/ carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing
    Hejazi, MA ; Tong, W ; Stacey, A ; Soto-Breceda, A ; Ibbotson, MR ; Yunzab, M ; Maturana, MI ; Almasi, A ; Jung, YJ ; Sun, S ; Meffin, H ; Fang, J ; Stamp, MEM ; Ganesan, K ; Fox, K ; Rifai, A ; Nadarajah, A ; Falahatdoost, S ; Prawer, S ; Apollo, NV ; Garrett, DJ (Elsevier, 2020-02-01)
    Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.
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    Stimulation Strategies for Improving the Resolution of Retinal Prostheses.
    Tong, W ; Meffin, H ; Garrett, DJ ; Ibbotson, MR (Frontiers Media, 2020-03-26)
    Electrical stimulation using implantable devices with arrays of stimulating electrodes is an emerging therapy for neurological diseases. The performance of these devices depends greatly on their ability to activate populations of neurons with high spatiotemporal resolution. To study electrical stimulation of populations of neurons, retina serves as a useful model because the neural network is arranged in a planar array that is easy to access. Moreover, retinal prostheses are under development to restore vision by replacing the function of damaged light sensitive photoreceptors, which makes retinal research directly relevant for curing blindness. Here we provide a progress review on stimulation strategies developed in recent years to improve the resolution of electrical stimulation in retinal prostheses. We focus on studies performed with explanted retinas, in which electrophysiological techniques are the most advanced. We summarize achievements in improving the spatial and temporal resolution of electrical stimulation of the retina and methods to selectively stimulate neurons with different visual functions. Future directions for retinal prostheses development are also discussed, which could provide insights for other types of neuromodulatory devices in which high-resolution electrical stimulation is required.
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    Synaptic Basis for Contrast-Dependent Shifts in Functional Identity in Mouse V1
    Yunzab, M ; Choi, V ; Meffin, H ; Cloherty, SL ; Priebe, NJ ; Ibbotson, MR (Society for Neuroscience., 2019-03)
    A central transformation that occurs within mammalian visual cortex is the change from linear, polarity-sensitive responses to nonlinear, polarity-insensitive responses. These neurons are classically labelled as either simple or complex, respectively, on the basis of their response linearity (Skottun et al., 1991). While the difference between cell classes is clear when the stimulus strength is high, reducing stimulus strength diminishes the differences between the cell types and causes some complex cells to respond as simple cells (Crowder et al., 2007; van Kleef et al., 2010; Hietanen et al., 2013). To understand the synaptic basis for this shift in behavior, we used in vivo whole-cell recordings while systematically shifting stimulus contrast. We find systematic shifts in the degree of complex cell responses in mouse primary visual cortex (V1) at the subthreshold level, demonstrating that synaptic inputs change in concert with the shifts in response linearity and that the change in response linearity is not simply due to the threshold nonlinearity. These shifts are consistent with a visual cortex model in which the recurrent amplification acts as a critical component in the generation of complex cell responses (Chance et al., 1999).
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    Upper stimulation threshold for retinal ganglion cell activation
    Meng, K ; Fellner, A ; Rattay, F ; Ghezzi, D ; Meffin, H ; Ibbotson, MR ; Kameneva, T (IOP PUBLISHING LTD, 2018-08)
    OBJECTIVE: The existence of an upper threshold in electrically stimulated retinal ganglion cells (RGCs) is of interest because of its relevance to the development of visual prosthetic devices, which are designed to restore partial sight to blind patients. The upper threshold is defined as the stimulation level above which no action potentials (direct spikes) can be elicited in electrically stimulated retina. APPROACH: We collected and analyzed in vitro recordings from rat RGCs in response to extracellular biphasic (anodic-cathodic) pulse stimulation of varying amplitudes and pulse durations. Such responses were also simulated using a multicompartment model. MAIN RESULTS: We identified the individual cell variability in response to stimulation and the phenomenon known as upper threshold in all but one of the recorded cells (n  =  20/21). We found that the latencies of spike responses relative to stimulus amplitude had a characteristic U-shape. In silico, we showed that the upper threshold phenomenon was observed only in the soma. For all tested biphasic pulse durations, electrode positions, and pulse amplitudes above lower threshold, a propagating action potential was observed in the distal axon. For amplitudes above the somatic upper threshold, the axonal action potential back-propagated in the direction of the soma, but the soma's low level of hyperpolarization prevented action potential generation in the soma itself. SIGNIFICANCE: An upper threshold observed in the soma does not prevent spike conductance in the axon.
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    Feasibility of Nitrogen Doped Ultrananocrystalline Diamond Microelectrodes for Electrophysiological Recording From Neural Tissue
    Wong, YT ; Ahnood, A ; Maturana, M ; Kentler, W ; Ganesan, K ; Grayden, DB ; Meffin, H ; Prawer, S ; Ibbotson, MR ; Burkitt, AN (FRONTIERS MEDIA SA, 2018-06-22)
    Neural prostheses that can monitor the physiological state of a subject are becoming clinically viable through improvements in the capacity to record from neural tissue. However, a significant limitation of current devices is that it is difficult to fabricate electrode arrays that have both high channel counts and the appropriate electrical properties required for neural recordings. In earlier work, we demonstrated nitrogen doped ultrananocrystalline diamond (N-UNCD) can provide efficacious electrical stimulation of neural tissue, with high charge injection capacity, surface stability and biocompatibility. In this work, we expand on this functionality to show that N-UNCD electrodes can also record from neural tissue owing to its low electrochemical impedance. We show that N-UNCD electrodes are highly flexible in their application, with successful recordings of action potentials from single neurons in an in vitro retina preparation, as well as local field potential responses from in vivo visual cortex tissue. Key properties of N-UNCD films, combined with scalability of electrode array fabrication with custom sizes for recording or stimulation along with integration through vertical interconnects to silicon based integrated circuits, may in future form the basis for the fabrication of versatile closed-loop neural prostheses that can both record and stimulate.
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    Epiretinal Electrical Stimulation and the Inner Limiting Membrane in Rat Retina
    Cloherty, SL ; Wong, RCS ; Hadjinicolaou, AE ; Meffin, H ; Ibbotson, MR ; O'Brien, BJ (IEEE, 2012)
    In this paper we aim to quantify the effect of the inner limiting membrane (ILM) of the retina on the thresholds for epiretinal electrical stimulation of retinal ganglion cells by a microelectronic retinal prosthesis. A pair of bipolar stimulating electrodes was placed either above (on the epiretinal surface) or below the ILM while we made whole-cell patch-clamp recordings from retinal ganglion cells in an isolated rat retinal whole-mount preparation. Across our cell population we found no significant difference in the median threshold stimulus amplitudes when the stimulating electrodes were placed below as opposed to above the ILM (p = 0.08). However, threshold stimulus amplitudes did tend to be lower when the stimulating electrodes were placed below the ILM (30 µA vs 56 µA).