Anatomy and Neuroscience - Research Publications

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    Selective retinal ganglion cell vulnerability in older mice exposed to acute intraocular pressure elevation and the potential involvement of the P2X7-receptor
    Wang, AY ; Vessey, KA ; Bui, BV ; Wong, VHY ; Lee, PY ; Fletcher, EL (Association for Research in Vision and Ophthalmology, 2019-07-01)
    Purpose : P2X7-receptors may contribute to retinal ganglion cell (RGC) death in glaucoma. We examined RGC function following acute intraocular pressure (IOP) elevation in older C57BL/6 (WT) mice and P2X7-receptor knockout (P2X7-KO) mice using a multielectrode array (MEA). Methods : In 13-month-old WT (n=15) and P2X7-KO mice (n=9), the anterior chamber of one eye was cannulated (50μm glass micropipette connected to a height-adjustable Hanks balanced salt solution reservoir) to increase IOP to 50 mmHg for 30 minutes. The contralateral eye was cannulated without increasing IOP (sham). Three days following injury, mice were dark-adapted over-night and retinae were mounted onto an MEA to record RGC spontaneous activityand light-evoked responses. Full field stimuli were 1 second flashes modulated between 0 and 1066 photoisomerisations/rod/sec. To test frequency responsiveness, full field light ON and OFF components were modulated from 1 to 30 Hz. Receptive fields were mapped by calculating the spike triggered average in response to a 32x32 checkerboard stimulus (70µm squares) presented at 12 Hz, with mean luminance of 517 photoisomerations/rod/sec. Cells were analyzed and sorted using Spike2 and classified into ON, OFF, ON-OFF and non-responsive types based on peak firing during light on and off full-field stimuli. Results : In WT mice there was a significant reduction in spontaneous activity (p<0.05) and full-field-evoked spike rates (p<0.05) for OFF RGCs after IOP stress compared to OFF cells of sham eyes. These changes appear to be subtype-specific as ON and ON-OFF cells showed no change in response. There were no further effects of IOP at higher temporal frequencies of full field stimulus, nor were there changes in receptive field size. In P2X7-KO mice, OFF RGCs in IOP stressed eyes showed significantly reduced spontaneous rate (p<0.05) compared to OFF RGCs in WT sham eyes, much like the effect of IOP stress on WT OFF cells. Additionally, ON RGCs from P2X7-KO eyes subjected to IOP stress showed a significant decrease in peak spike rate compared to P2X7-KO sham eyes (p<0.05). Conclusions : These results suggest that even a short period of mild IOP stress can have long lasting effect on RGC function, particularly that of OFF-RGCs. In contrast to previous studies, P2X7-KO did not prevent RGC functional deficits associated with acute mild IOP elevation.
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    A tractable preclinical model of optic nerve demyelination
    van Wijngaarden, P ; Paul, JP ; Wong, VHY ; Bui, BV ; Merson, TD (Association for Research in Vision and Ophthalmology, 2019-07-01)
    Purpose : Progress in the development of therapies to enhance remyelination in demyelinating diseases has been hampered by a lack of appropriate preclinical models - functional measures are often lacking or variable. We sought to develop a tractable and reproducible model of optic nerve demyelination with precise structural and functional measures. Methods : Oligodendrocytes of MBP-DTR 100a transgenic mice express diphtheria toxin receptor (DTR) and systemic diphtheria toxin (DT) administration induces diffuse demyelination of the central nervous system. In the present study we used retrobulbar DT injection to induce focal demyelination of the optic nerves of 3-month-old MBP-DTR 100a mice. Dose optimisation: anaesthetised mice underwent unilateral retrobulbar DT injection with 5, 10 or 15ng/kg DT (n=7 per dose, 1 µL per injection). Tissues were harvested three weeks after injection. Time-course study: Following baseline visual evoked potential (VEP) recording, electroretinogram (ERG) and optical coherence tomography (OCT), mice underwent retrobulbar DT injection with 15ng/kg DT or 1µL PBS. Follow-up measurements were taken at 2 (n=5 DT, 5 PBS), 4 (n=6 DT, 6 PBS), 8 (n=9 DT, 9 PBS) or 12-weeks (n=7 DT, 7 PBS). Animals were culled at each timepoint for tissue analysis. Tissue analysis: Optic nerves were resin embedded, sectioned (1µm) and stained with toluidine blue for myelin analysis, or cryosectioned for immunofluorescence, and retinas were flat-mounted for ganglion cell counts. Results : 3 weeks after injection with 15ng/kg DT, optic nerves showed colocalisation of activated caspase 3 & olig2, consistent with the apoptosis of oligodendroglia. Gliosis and axonal degeneration were evident.
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    The effect of TrkB receptor knockdown on mouse retinal ganglion cell function and their response to acute mild intraocular pressure stress
    Wong, VHY ; Wang, A ; Nguyen, CTO ; Lim, JKH ; Nicholson, M ; Xiao, J ; Murray, S ; Bui, BV (Association for Research in Vision and Ophthalmology, 2019-07-01)
    Purpose : To examine the effect of tropomyosin receptor kinase B (TrkB) receptor removal on basal retinal ganglion cell (RGC) function and recovery from acute intraocular pressure (IOP) stress following conditional deletion of neuronal-specific TrkB receptors in adult mice. Methods : Conditional TrkB receptor knockout (KO) from Thy-1 positive neurons was induced via daily tamoxifen injections (100 ul i.p. 75mg/kg, 5 days) in 3-month old Thy1-GFP CreERT2+/- TrkBfl/fl transgenic (TrkB KO n=12) and control CreERT2-/- TrkBfl/fl mice (n=12). Four weeks later, one eye was exposed to controlled IOP stress of 50mmHg for 30 minutes, achieved via anterior chamber cannulation (50 μm glass micropipette connected to height-adjustable Hanks balanced salt solution reservoir; 80:10mg/kg ketamine:xylazine). After 7 days of recovery, retinal function (full-field electroretinogram -5.53 – 2.07 log cd.s/m2) and structure (optical coherence tomography) were assessed in sedated mice. Following in vivo assays, eyes were enucleated for immunohistochemical assessment of TrkB receptor KO efficiency using confocal microscopy. Unpaired t-test and two-way ANOVA were used for statistical analysis. Results : TrkB receptor expression was largely confined to the ganglion cell layers and reduced by 81.3±5.8% in TrkB KO retinas compared to controls (P<0.05). Deletion of TrkB receptors significantly reduced RGC-mediated negative scotopic threshold response (nSTR -39.1±13.7% P<0.05, positive STR -38.0±12.1% P=0.05). No changes in photoreceptor (amplitude P>0.05, sensitivity P>0.05) and bipolar cell (amplitude P>0.05, sensitivity P>0.05) function. At day 7 post-IOP stress, photoreceptor and bipolar cell responses recovered back to baseline whilst RGC function did not (pSTR P<0.05; nSTR P<0.05). This effect was similar for both genotypes. TrkB KO did not affect total retinal, retinal nerve fibre, ganglion cell and inner plexiform layer thicknesses compared with control retina (P>0.05). Conclusions : Conditional removal of TrkB receptors in adult mice suggests that TrkB is critical for the ongoing maintenance of ganglion cell function. Specific changes in RGC morphology, synapse expression or intrinsic excitability associated with TrkB deficiency remain to be elucidated. It appears that TrkB receptors do not play an integral role in recovery from a single episode of mild IOP stress.
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    Assessing esport candidacy for critical thinking education
    Post, G ; Birt, J (University of New England, Armidale, 2020-12-01)
    Critical thinking in education is mainstream with ever increasing industry support for soft skills and capacity for graduates to solve problems, plan strategy, make decisions and communicate creatively. However, teaching and assessing critical thinking is resource intensive especially when scaling to large remote or online classes. Often, the solutions are bespoke, custom outcomes for a single classroom that are expensive to scale. Commercial computer games and esports may offer a solution. In this paper we aim to define critical thinking in education and how this relates to skills in esports, including decision making, problem solving, making a game plan, developing strategy and communication. To achieve this, we propose a conceptual framework to assess effectiveness of esports in teaching critical thinking using an adapted digital game-based learning framework and the learning goals of critical thinking. We support the framework with an esport case example of Rocket League with a lesson plan.
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    Challenges for Computational Stem Cell Biology: A Discussion for the Field
    Rackham, O ; Cahan, P ; Mah, N ; Morris, S ; Ouyang, JF ; Plant, AL ; Tanaka, Y ; Wells, CA (CELL PRESS, 2021-01-12)
    The first meetup for Computational Stem Cell Biologists was held at the 2020 annual meeting of the International Society for Stem Cell Research. The discussions highlighted opportunities and barriers to computational stem cell research that require coordinated action across the stem cell sector.
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    Simulating bidirectional peripheral neural interfaces in EIDORS
    Eiber, CD ; Keast, JR ; Osborne, PB (IEEE, 2020-01-01)
    Bioelectronic neural interfaces that deliver adaptive therapeutic stimulation in an intelligent manner must be able to sense and stimulate activity within the same nerve. Existing minimally-invasive peripheral neural interfaces can provide a read-out of the aggregate level of activity via electrical recordings of nerve activity, but these recordings are limited in terms of their specificity. Computational simulations can provide fine-grained insight into the contributions of different neural populations to the extracellular recording, but integration of the signals from individual nerve fibers requires knowledge of spread of current in the complex (heterogenous, anisotropic) extracellular space. We have developed a model which uses the open-source EIDORS package for extracellular stimulation and recording in the pelvic nerve. The pelvic nerve is the primary source of autonomic innervation to the pelvic organs, and a prime target for electrical stimulation to treat a variety of voiding disorders. We simulated recordings of spontaneous and electrically-evoked activity using biophysical models for myelinated and unmyelinated axons. As expected, stimulus thresholds depended strongly on both fibre type and electrode-fibre distance. In conclusion, EIDORS can be used to accurately simulate extracellular recording in complex, heterogenous neural geometries.
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    The Electric Field System of a Macular Ion Channel Plaque
    Hales, C ; Grayden, D ; Quiney, H (IEEE, 2011-01-01)
    Recent empirical neuroscience evidence increasingly supports an active role for the endogenous electromagnetic (EM) field system of brain tissue. These results undermine the long-held view that the field system is a causally inert byproduct of action potential and synapse electrochemical activity. The dominant originating mechanism for the endogenous EM field remains undetermined. The new observations make the isolation of an unambiguous original EM field source a matter of some urgency. As part of the process of elaboration of the field systems produced by coherent transmembrane filamentary currents (the most plausible original mechanism), this paper looks at the contribution by a localized density of cooperating ion channels in the form of the macular synaptic plaque engaged in conducting a post-synaptic current. The method uses the volume conduction formalism driven by filamentary currents that stand in for ion channels. Not surprisingly, the result is a pulsing dipole. Despite its extreme material abstraction, the result forms one of the basic mechanisms for future models capable of revealing whole-neuron and network-level endogenous EM field system.
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    Acoustic analysis of the effects of 24 hours of sustained wakefulness
    Vogel, AP ; Fletcher, J ; Maruff, P (Australasian Speech Science and Technology Association, 2010)
    The effect of 24 hours of sustained wakefulness on the speech of healthy adults is poorly documented. Therefore, speech samples were systematically acquired (e.g., every four hours) from 18 healthy adults over 24 hours. Stimuli included automated and extemporaneous tasks, sustained vowel and a read passage. Measures of timing and frequency were derived acoustically using Praat and significant changes were observed on all tasks. The effect of fatigue on speech was found to be strongest just before dawn (after 22 hours). Key features of timing (e.g., mean pause length), frequency (e.g., F4 variation) and power (alpha ratio) changed as a function of increasing levels of fatigue. Index Terms: fatigue, voice, tiredness, clinical marker
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    Precision Medicine: Dawn of Supercomputing in ‘omics Research
    Reumann, M ; Holt, KE ; Inouye, M ; Stinear, T ; Goudey, B ; Abraham, G ; WANG, Q ; Shi, F ; Kowalczyk, A ; Pearce, A ; Isaac, A ; Pope, BJ ; Butzkueven, H ; Wagner, J ; Moore, S ; Downton, M ; Church, PC ; Turner, SJ ; Field, J ; Southey, M ; Bowtell, D ; Schmidt, D ; Makalic, E ; Zobel, J ; Hopper, J ; Petrovski, S ; O'Brien, T (eResearch Australasia, 2011)