Optometry and Vision Sciences - Research Publications
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ItemSynaptic Basis for Contrast-Dependent Shifts in Functional Identity in Mouse V1(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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ItemUpper stimulation threshold for retinal ganglion cell activation(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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ItemFeasibility of Nitrogen Doped Ultrananocrystalline Diamond Microelectrodes for Electrophysiological Recording From Neural Tissue(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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ItemNeural basis of forward flight control and landing in honeybees(NATURE PORTFOLIO, 2017-11-06)The impressive repertoire of honeybee visually guided behaviors, and their ability to learn has made them an important tool for elucidating the visual basis of behavior. Like other insects, bees perform optomotor course correction to optic flow, a response that is dependent on the spatial structure of the visual environment. However, bees can also distinguish the speed of image motion during forward flight and landing, as well as estimate flight distances (odometry), irrespective of the visual scene. The neural pathways underlying these abilities are unknown. Here we report on a cluster of descending neurons (DNIIIs) that are shown to have the directional tuning properties necessary for detecting image motion during forward flight and landing on vertical surfaces. They have stable firing rates during prolonged periods of stimulation and respond to a wide range of image speeds, making them suitable to detect image flow during flight behaviors. While their responses are not strictly speed tuned, the shape and amplitudes of their speed tuning functions are resistant to large changes in spatial frequency. These cells are prime candidates not only for the control of flight speed and landing, but also the basis of a neural 'front end' of the honeybee's visual odometer.
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ItemElectrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons(PUBLIC LIBRARY SCIENCE, 2018-02)Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell's spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear.
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ItemTechniques for Processing Eyes Implanted with a Retinal Prosthesis for Localized Histopathological Analysis: Part 2 Epiretinal Implants with Retinal Tacks(JOURNAL OF VISUALIZED EXPERIMENTS, 2015-02)Retinal prostheses for the treatment of certain forms of blindness are gaining traction in clinical trials around the world with commercial devices currently entering the market. In order to evaluate the safety of these devices, in preclinical studies, reliable techniques are needed. However, the hard metal components utilised in some retinal implants are not compatible with traditional histological processes, particularly in consideration for the delicate nature of the surrounding tissue. Here we describe techniques for assessing the health of the eye directly adjacent to a retinal implant secured epiretinally with a metal tack. Retinal prostheses feature electrode arrays in contact with eye tissue. The most commonly used location for implantation is the epiretinal location (posterior chamber of the eye), where the implant is secured to the retina with a metal tack that penetrates all the layers of the eye. Previous methods have not been able to assess the proximal ocular tissue with the tack in situ, due to the inability of traditional histological techniques to cut metal objects. Consequently, it has been difficult to assess localized damage, if present, caused by tack insertion. Therefore, we developed a technique for visualizing the tissue around a retinal tack and implant. We have modified an established technique, used for processing and visualizing hard bony tissue around a cochlear implant, for the soft delicate tissues of the eye. We orientated and embedded the fixed eye tissue, including the implant and retinal tack, in epoxy resin, to stabilise and protect the structure of the sample. Embedded samples were then ground, polished, stained, and imaged under various magnifications at incremental depths through the sample. This technique allowed the reliable assessment of eye tissue integrity and cytoarchitecture adjacent to the metal tack.
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ItemIn vivo biocompatibility of boron doped and nitrogen included conductive-diamond for use in medical implants(WILEY, 2016-01)Recently, there has been interest in investigating diamond as a material for use in biomedical implants. Diamond can be rendered electrically conducting by doping with boron or nitrogen. This has led to inclusion of boron doped and nitrogen included diamond elements as electrodes and/or feedthroughs for medical implants. As these conductive device elements are not encapsulated, there is a need to establish their clinical safety for use in implants. This article compares the biocompatibility of electrically conducting boron doped diamond (BDD) and nitrogen included diamond films and electrically insulating poly crystalline diamond films against a silicone negative control and a BDD sample treated with stannous octoate as a positive control. Samples were surgically implanted into the back muscle of a guinea pig for a period of 4-15 weeks, excised and the implant site sectioned and submitted for histological analysis. All forms of diamond exhibited a similar or lower thickness of fibrotic tissue encapsulating compared to the silicone negative control samples. All forms of diamond exhibited similar or lower levels of acute, chronic inflammatory, and foreign body responses compared to the silicone negative control indicating that the materials are well tolerated in vivo.
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ItemEpiretinal Electrical Stimulation and the Inner Limiting Membrane in Rat Retina(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).
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ItemRetinal ganglion cells electrophysiology: the effect of cell morphology on impulse waveform(IEEE, 2013)There are 16 morphologically defined classes of rats retinal ganglion cells (RGCs). Using computer simulation of a realistic anatomically correct A1 mouse RGC, we investigate the effect of the cell's morphology on its impulse waveform, using the first-, and second-order time derivatives as well as the phase plot features. Using whole cell patch clamp recordings, we recorded the impulse waveform for each of the rat RGCs types. While we found some clear differences in many features of the impulse waveforms for A2 and B2 cells compared to other cell classes, many cell types did not show clear differences.