ORCID Profile
0000-0002-2260-5532
Current Organisations
Australian National University
,
The University of Newcastle
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biomaterials | Cellular nervous system | Biomedical engineering | Cellular Interactions (Incl. Adhesion, Matrix, Cell Wall) | Materials Engineering | Diagnostic Applications | Alloy Materials |
ANZSRC Socio-Economic Objective (SEO)
Concentrating processes of other base metal ores | Energy transformation not elsewhere classified | Field crops |
Related Links
Publications
The Vestibular System
Publisher: SAGE Publications, Inc.
Date: 2019
Developmental changes in pacemaker currents in mouse locus coeruleus neurons
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.BRAINRES.2011.09.053
Abstract: The present study compares the electrophysiological properties and the primary pacemaker currents that flow during the interspike interval in locus coeruleus (LC) neurons from infant (P7-12 days) and young adult (8-12 weeks) mice. The magnitude of the primary pacemaker currents, which consist of an excitatory TTX-sensitive Na(+) current and an inhibitory voltage-dependent K(+) current, increased in parallel during development. We found no evidence for the involvement of hyperpolarization-activated (I(H)) or Ca(2+) currents in pacemaking in infant or adult LC neurons. The incidence of TTX-resistant spikes, observed during current cl recordings, was greater in adult neurons. Neurons from adult animals also showed an increase in voltage fluctuations, during the interspike interval, as revealed in the presence of the K(+) channel blocker, 4-AP (1mM). In summary, our results suggest that mouse LC neurons undergo changes in basic electrophysiological properties during development that influence pacemaking and hence spontaneous firing in LC neurons.
Attenuated glycine receptor function reduces excitability of mouse medial vestibular nucleus neurons
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.NEUROSCIENCE.2010.06.040
Abstract: Spontaneous activity in medial vestibular nucleus (MVN) neurons is modulated by synaptic inputs. These inputs are crucial for maintaining gaze and posture and contribute to vestibular compensation after lesions of peripheral vestibular organs. We investigated how chronically attenuated glycinergic input affects excitability of MVN neurons. To this end we used three mouse strains (spastic, spasmodic, and oscillator), with well-characterized naturally occurring mutations in the inhibitory glycine receptor (GlyR). First, using whole-cell patch-cl recordings, we demonstrated that the litude of the response to rapidly applied glycine was dramatically reduced by 25 to 90% in MVN neurons from mutant mice. We next determined how reduced GlyR function affected MVN neuron output. Neurons were classified using two schemas: (1) the shape of their action potential afterhyperpolarization (AHP) and (2) responses to hyperpolarizing current injection. In the first schema, neurons were classified as types A, B and C. The prevalence of type C neurons in the mutant strains was significantly increased. In the second schema, the proportion of neurons lacking post inhibitory rebound firing (PRF-deficient) was increased. In both schemas an increase in AHP litude was a common feature of the augmented neuron group (type C, PRF-deficient) in the mutant strains. We suggest increased AHP litude reduces overall excitability in the MVN and thus maintains network function in an environment of reduced glycinergic input.
Quantal size is correlated with receptor cluster area at glycinergic synapses in the rat brainstem
Publisher: Wiley
Date: 04-1999
DOI: 10.1111/J.1469-7793.1999.0505V.X
Abstract: 1. Whole-cell patch electrode recordings of glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were obtained in neurons of the rat anteroventral cochlear nucleus (AVCN). Mean mIPSC peak litude was found to vary considerably between AVCN neurons (range, -19.1 to -317.9 pA mean +/- s.d., -159.1 +/- 100.7 pA 14 cells). 2. Immunolabelling of glycinergic receptor clusters in AVCN neurons was performed using antibodies against the glycine receptor clustering protein gephyrin. Measurements of the area of gephyrin immunoreactive clusters were obtained using confocal fluorescence microscopy. These measurements showed a large variability in cluster area, not only in the same cell (mean coefficient of variation, c.v., 0.66 +/- 0.18 16 cells), but also in mean cluster area between cells (range, 0.21-0.84 microm2 16 cells). 3. A possible relationship between mIPSC litude and receptor cluster area was investigated in a further series of experiments, in which mIPSCs recordings and immunolabelling of glycine receptor clusters were obtained for the same cells. In these experiments, AVCN neurons were identified using intracellular labelling with neurobiotin. Successful results using a combination of whole-cell recordings, neurobiotin identification and immunolabelling were obtained for a total of 10 AVCN neurons. Analysis of the results revealed a positive, statistically significant correlation between mean receptor cluster size and mean mIPSC litude (P < 0.05, 10 cells, Spearman's correlation test). 4. These results provide direct experimental evidence supporting a hypothesis of central glycinergic transmission in which synaptic strength may be regulated by changes in the size of the postsynaptic receptor region.
Properties of Deiters’ neurons and inhibitory synaptic transmission in the mouse lateral vestibular nucleus
Publisher: American Physiological Society
Date: 07-2022
Abstract: Deiters’ neurons within the lateral vestibular nucleus project the length of the spinal cord and activate antigravity extensor muscles. Deiters’ neurons were characterized anatomically and physiologically in mice. Deiters’ neurons are tonically active, have homogeneous intrinsic membrane properties, including low input resistance, and receive significant GABA A ergic synaptic inputs. Deiters’ neurons show little modulation in response to current injection. These features are consistent with Deiters’ neurons responding to perturbations to maintain posture and balance.
Glycinergic mIPSCs in mouse and rat brainstem auditory nuclei: modulation by ruthenium red and the role of calcium stores.
Publisher: Wiley
Date: 02-2003
DOI: 10.1113/JPHYSIOL.2002.035071
Abstract: Spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in central neurons are usually highly variable in litude due to many factors such as intrinsic postsynaptic channel fluctuations at each release site, site-to-site variability between release sites, electrotonic attenuation due to variable dendritic locations of synapses, and the possibility of synchronous multivesicular release. A detailed knowledge of these factors is essential for the interpretation of mIPSC litude distributions and mean quantal size. We have studied glycinergic mIPSCs in two auditory brainstem nuclei, the rat anteroventral cochlear nucleus (AVCN) and the mouse medial nucleus of the trapezoid body (MNTB). Our previous results have demonstrated the location of glycinergic synapses on these neurons to be somatic, thus avoiding electrotonic complications. Spontaneous glycinergic mIPSCs were recorded from AVCN and MNTB neurons in brainstem slices, in the presence of TTX to block action potentials, and 6-cyano-7-nitroquinoxaline-2, 3-dione, (+/-)-2-amino-5-phosphonopentanoic acid and bicuculline to block glutamatergic and GABAergic synaptic currents. Ruthenium red (RuR), which was used to increase the frequency of mIPSCs, significantly changed the shape of most (90 %) mIPSC litude distributions by increasing the proportion of large- litude mIPSCs. The possibility was investigated (following previous evidence at GABAergic synapses) that large- litude glycinergic mIPSCs are due to synchronous multivesicular release initiated by presynaptic calcium sparks from ryanodine-sensitive calcium stores. Interval analysis of mIPSCs indicated that the number of potentially undetected (asynchrony 150 pA), arguing against a significant role for presynaptic calcium stores. Our results support previous evidence suggesting that RuR increases miniature postsynaptic current (mSC) frequency by a mechanism that does not involve presynaptic calcium stores. Our results also indicate that at glycinergic synapses in the AVCN and MNTB, site-to-site variability in mIPSC litude, rather than multivesicular release, is a major factor underlying the large range of litudes of glycinergic mIPSCs.
Molecular and Functional Changes to Postsynaptic Cholinergic Signaling in the Vestibular Sensory Organs of Aging C57BL/6 Mice
Publisher: Oxford University Press (OUP)
Date: 25-02-2023
Abstract: Cholinergic circuits in the central nervous system are vulnerable to age-related functional decline, but it is not known if aging impacts cholinergic signaling in the vestibular sensory organs, which are critically important to balance maintenance and visual gaze stability. We have previously shown cholinergic neurotransmission between vestibular efferent terminals and type II mechanosensory hair cells requires the alpha9 (Chrna9) nicotinic receptor subunit. Homozygous knockout of the alpha9 subunit causes vestibulo-ocular reflex adaptation deficits that mirror those observed in aged mice. This prompted examination of cholinergic signaling in the vestibular sensory organs of aged mice. We confirmed older (& months) mice had impaired performance in a balance beam task compared to young (3–4 months) adult mice. While there was no qualitative loss of cholinergic axon varicosities in the crista ullaris of old mice, qPCR analysis revealed reduced expression of nicotinic receptor subunit genes Chrna1, Chrna9, and Chrna10 in the cristae of old relative to young mice. Functionally, single-cell patch cl recordings taken from type II vestibular hair cells exposed to acetylcholine show reduced conductance through alpha9/10 subunit-containing nicotinic receptors in older mice, despite preserved passive membrane properties and voltage-activated conductances. These findings suggest that cholinergic signaling in the peripheral vestibular sensory organs is vulnerable to aging processes, manifesting in dynamic molecular and functional age-related changes. Given the importance of these organs to our everyday activities, and the dramatic increase in fall incidence in the older, further investigation into the mechanisms of altered peripheral vestibular function in older humans is warranted.
Anatomical and physiological development of the human inner ear
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.HEARES.2016.02.004
Abstract: We describe the development of the human inner ear with the invagination of the otic vesicle at 4 weeks gestation (WG), the growth of the semicircular canals from 5 WG, and the elongation and coiling of the cochlea at 10 WG. As the membranous labyrinth takes shape, there is a concomitant development of the sensory neuroepithelia and their associated structures within. This review details the growth and differentiation of the vestibular and auditory neuroepithelia, including synaptogenesis, the expression of stereocilia and kinocilia, and innervation of hair cells by afferent and efferent nerve fibres. Along with development of essential sensory structures we outline the formation of crucial accessory structures of the vestibular system - the cupula and otolithic membrane and otoconia as well as the three cochlea compartments and the tectorial membrane. Recent molecular studies have elaborated on classical anatomical studies to characterize the development of prosensory and sensory regions of the fetal human cochlea using the transcription factors, PAX2, MAF-B, SOX2, and SOX9. Further advances are being made with recent physiological studies that are beginning to describe when hair cells become functionally active during human gestation. This article is part of a Special Issue entitled .
Electrical maturation of spinal neurons in the human fetus: Comparison of ventral and dorsal horn
Publisher: American Physiological Society
Date: 11-2015
Abstract: The spinal cord is critical for modifying and relaying sensory information to, and motor commands from, higher centers in the central nervous system to initiate and maintain contextually relevant locomotor responses. Our understanding of how spinal sensorimotor circuits are established during in utero development is based largely on studies in rodents. In contrast, there is little functional data on the development of sensory and motor systems in humans. Here, we use patch-cl electrophysiology to examine the development of neuronal excitability in human fetal spinal cords (10–18 wk gestation WG). Transverse spinal cord slices (300 μm thick) were prepared, and recordings were made, from visualized neurons in either the ventral (VH) or dorsal horn (DH) at 32°C. Action potentials (APs) could be elicited in VH neurons throughout the period examined, but only after 16 WG in DH neurons. At this age, VH neurons discharged multiple APs, whereas most DH neurons discharged single APs. In addition, at 16–18 WG, VH neurons also displayed larger AP and after-hyperpolarization litudes than DH neurons. Between 10 and 18 WG, the intrinsic properties of VH neurons changed markedly, with input resistance decreasing and AP and after-hyperpolarization litudes increasing. These findings are consistent with the hypothesis that VH motor circuitry matures more rapidly than the DH circuits that are involved in processing tactile and nociceptive information.
An Isolated Semi-intact Preparation of the Mouse Vestibular Sensory Epithelium for Electrophysiology and High-resolution Two-photon Microscopy
Publisher: MyJove Corporation
Date: 13-06-2013
DOI: 10.3791/50471
An increase in glycinergic quantal amplitude and frequency during early vestibular compensation in mouse
Publisher: American Physiological Society
Date: 2010
Abstract: The process of vestibular compensation includes both behavioral and neuronal recovery after unilateral loss of peripheral vestibular organs. The mechanisms that underlie this process are poorly understood. Previous research has shown the presence of both γ-aminobutyric acid type A (GABA A ) and glycine receptors in the medial vestibular nuclei (MVN). It has been suggested that inhibitory transmission mediated by these receptors may have a role in recovery during vestibular compensation. This study investigated changes in fast inhibitory synaptic transmission of GABA A ergic and glycinergic quantal events after unilateral labyrinthectomy (UL) at three different time points. Mice were anesthetized and peripheral vestibular organs were removed from one side of the head. After recovery, transverse brain stem sections (300 μm) were prepared from mice that had undergone UL either 4 hours, 2 days, or 7 days earlier. Our experiments do not show evidence for alterations in synaptic GABA A receptor properties in MVN neurons after UL at any time point investigated. In contrast, during early vestibular compensation (4 hours post UL) there is a significant increase in the glycinergic quantal current litude in contralesional MVN neurons compared with control. Our results also show an increase in the frequency of glycinergic quantal events of both ipsi- and contralesional MVN neurons during this early period. We suggest that changes in both pre- and postsynaptic glycine receptor mediated inhibitory synaptic transmission after sensory loss is an important mechanism by which neuronal discharge patterns can be modulated.
Anatomical and physiological properties of pelvic ganglion neurons in female mice
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.AUTNEU.2008.03.001
Abstract: Most neurons that regulate motility and blood flow in female pelvic organs are located within pelvic (paracervical) ganglia. In this study we investigated the anatomical and physiological properties of neurons within mouse (C57/Bl/6) paracervical ganglia. Most neurons showed immunoreactivity for choline acetyl transferase (CHAT) and were presumably cholinergic. Few neurons (approximately 5%) were tyrosine hydroxylase (TH) positive. Immunohistochemical labelling for microtubule associated protein 2 showed most neurons had small somata (cross sectional area approximately 300 microm(2)) and lacked dendrites. Action potential (AP) discharge characteristics, determined by depolarising current step injection, revealed most neurons (70%) adapted rapidly to depolarising current injection and were classified as "phasic". The remaining neurons discharged APs throughout the current step and were classified as "tonic". Membrane properties and current-voltage relationships were similar in phasic and tonic neurons, however the afterhyperpolarisation was significantly smaller in tonic neurons. Stimulation of preganglionic axons usually evoked a single strong preganglionic input (21/27 and 9/10 for pelvic and hypogastric nerves, respectively). In 19 preparations where we tested for inputs from both nerves pelvic inputs predominated (23/45 neurons) and inputs via the hypogastric nerve were rarely observed (3/45 neurons). Together, our data indicate that most neurons within mouse paracervical ganglia are cholinergic and parasympathetic. As there is little anatomical or functional evidence for integration of preganglionic inputs we propose that the role of paracervical neurons is restricted to one of spatial lification or filtering of preganglionic inputs.
Organotypic culture of neonatal murine inner ear explants
Publisher: Frontiers Media SA
Date: 03-05-2019
Expression and Physiology of Voltage-Gated Sodium Channels in Developing Human Inner Ear
Publisher: Frontiers Media SA
Date: 25-10-2021
DOI: 10.3389/FNINS.2021.733291
Abstract: Sodium channel expression in inner ear afferents is essential for the transmission of vestibular and auditory information to the central nervous system. During development, however, there is also a transient expression of Na + channels in vestibular and auditory hair cells. Using qPCR analysis, we describe the expression of four Na + channel genes, SCN5A (Nav1.5), SCN8A (Nav1.6), SCN9A (Nav1.7), and SCN10A (Nav1.8) in the human fetal cristae ullares, utricle, and base, middle, and apex of the cochlea. Our data show distinct patterns of Na + channel gene expression with age and between these inner ear organs. In the utricle, there was a general trend toward fold-change increases in expression of SCN8A, SCN9A, and SCN10A with age, while the crista exhibited fold-change increases in SCN5A and SCN8A and fold-change decreases in SCN9A and SCN10A. Fold-change differences of each gene in the cochlea were more complex and likely related to distinct patterns of expression based on tonotopy. Generally, the relative expression of SCN genes in the cochlea was greater than that in utricle and cristae ullares. We also recorded Na + currents from developing human vestibular hair cells aged 10–11 weeks gestation (WG), 12–13 WG, and 14+ WG and found there is a decrease in the number of vestibular hair cells that exhibit Na + currents with increasing gestational age. Na + current properties and responses to the application of tetrodotoxin (TTX 1 μM) in human fetal vestibular hair cells are consistent with those recorded in other species during embryonic and postnatal development. Both TTX-sensitive and TTX-resistant currents are present in human fetal vestibular hair cells. These results provide a timeline of sodium channel gene expression in inner ear neuroepithelium and the physiological characterization of Na + currents in human fetal vestibular neuroepithelium. Understanding the normal developmental timeline of ion channel gene expression and when cells express functional ion channels is essential information for regenerative technologies.
Ketamine anesthesia helps preserve neuronal viability
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.JNEUMETH.2010.03.029
Abstract: The dissociative anesthetic ketamine that acts as an N-methyl-D-aspartate (NMDA) antagonist has been reported to improve neurological damage after experimental ischemic challenges. Here we show that deep anesthesia with ketamine before euthanasia by decapitation improves the quality of neonatal mouse neuronal brain slice preparations. Specifically we found that neurons of the locus coeruleus (LC) and hypoglossal motor neurons had significantly higher input resistances, and LC neurons that generally are difficult to voltage control, could be more reliably voltage cl ed compared to control neurons.
Is there an association between dietary intake and academic achievement: a systematic review
Publisher: Wiley
Date: 07-09-2016
DOI: 10.1111/JHN.12407
Abstract: The majority of literature examining the effect of dietary behaviour on academic achievement has focused on breakfast consumption only. Here, we aim to systematically review the literature investigating the broader effects of dietary intake and behaviours on school-aged children's academic achievement. A search was undertaken across seven databases using keywords. For studies to be included, they needed to be conducted in: school-aged children (5-18 years) assess and report: (i) a measure of academic performance (ii) a measure of dietary intake/behaviour and (iii) the association between dietary intake/behaviours and academic performance. Forty studies were included in the review. The majority of studies were cross-sectional in design (n = 33) and studied children aged >10 years, with very few reports in younger age groups. More than 30 different dietary assessment tools were used, with only 40% of those using a validated/standardised assessment method. Half the studies collected outcomes of academic achievement objectively from a recognised educational authority, whereas 10 studies used self-reported measures. The dietary outcomes most commonly reported to have positive associations with academic achievement were: breakfast consumption (n = 12) and global diet quality/meal patterns (n = 7), whereas negative associations reported with junk/fast food (n = 9). This review highlights that moderate associations exist for dietary intakes characterised by regular breakfast consumption, lower intakes of energy-dense, nutrient-poor foods and overall diet quality with respect to outcomes of academic achievement. Future studies should consider the use of validated dietary assessment methods and standardised reporting of academic achievement.
Vestibular System
Publisher: Elsevier
Date: 2012
Advanced Control of Drug Delivery for In Vivo Health Applications via Highly Biocompatible Self-Assembled Organic Nanoparticles
Publisher: American Chemical Society (ACS)
Date: 20-07-2021
Abstract: The use of nanostructured materials for targeted and controlled delivery of bioactive molecules is an attractive alternative to conventional drug administration protocols, enabling selective targeting of diseased cells, lower administered dosages, and reduced systemic side effects. Although a variety of nanocarriers have been investigated in recent years, electroactive organic polymer nanoparticles present several exciting advantages. Here we demonstrate that thin films created from nanoparticles synthesized from violanthrone-79, an n-type semiconducting organic material, can incorporate and release dexamethasone
Heat pulse excitability of vestibular hair cells and afferent neurons
Publisher: American Physiological Society
Date: 08-2016
Abstract: In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (Δ T ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were erse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q 10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (d T/d t) and an inward conduction current driven by Δ T. An iberiotoxin-sensitive inhibitory conduction current was also evoked by Δ T, rising in ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at −68 mV and in 67% of hair cells at −60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability.
A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications
Publisher: American Physiological Society
Date: 02-2020
Abstract: It has been over 60 years since peripheral efferent vestibular terminals were first identified in mammals, and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses have had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly 40 years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.
Blockade of Glycine Transporter-1 (GLYT-1) Potentiates NMDA Receptor-Mediated Synaptic Transmission in Hypoglossal Motorneurons
Publisher: American Physiological Society
Date: 10-2004
Abstract: NMDA receptor (NMDAR)-mediated spontaneous miniature excitatory postsynaptic currents (mEPSCs) are potentiated by exogenously applied glycine. In this study, we have investigated the effect of blocking glycine uptake on NMDAR-mediated responses from hypoglossal motorneurons (HMs) of rats. We have used N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)-propyl]sarcosine (NFPS 500 nM), an antagonist of glycine transporter-1 (GLYT1), to study the effect of blocking endogenous glycine uptake on NMDAR-mediated synaptic transmission. We show that the charge transfer of NMDAR-mediated mEPSCs was enhanced after NFPS application in neonate (P2-4) and juvenile rats (P8-11), but this enhancement was statistically significant only in the former group. Spontaneous and evoked EPSCs showed a significant increase in NMDAR-mediated charge transfer in both neonates and juveniles. The greater increase observed in spontaneous EPSCs may be due to increased release of glycine from glycinergic terminals in the absence of tetrodotoxin (TTX). Brief application of NMDA onto HMs showed that extrasynaptic NMDARs may be potentiated by NFPS only in the presence of extracellularly applied glycine. Immunohistochemistry of GLYT1 and -2 shows labeling throughout the hypoglossal nucleus. GLYT1 labeling is diffuse and becomes more intense and uniform during development consistent with its glial localization. In contrast, GLYT2 labeling is intense throughout the nucleus and increases in intensity with age. Our results demonstrate the glycine binding site of the NMDAR is not saturated in the brain stem slice during the first 2 wk of development. We suggest that modulation of glycine concentration by GLYT1 is an important mechanism to regulate NMDAR-mediated synaptic transmission.
The Ototoxic Potential of Cobalt From Metal-on-Metal Hip Implants: Objective Auditory and Vestibular Outcome
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-05-2019
DOI: 10.1097/AUD.0000000000000747
Abstract: During the past decade, the initial popularity of metal-on-metal (MoM) hip implants has shown a progressive decline due to increasingly reported implant failure and revision surgeries. Local as well as systemic toxic side effects have been associated with excessive metal ion release from implants, in which cobalt (Co) plays an important role. The rare condition of systemic cobaltism seems to manifest as a clinical syndrome with cardiac, endocrine, and neurological symptoms, including hearing loss, tinnitus, and imbalance. In most cases described in the literature, revision surgery and the subsequent drop in blood Co level led to (partial) alleviation of the symptoms, suggesting a causal relationship with Co exposure. Moreover, the ototoxic potential of Co has recently been demonstrated in animal experiments. Since its ototoxic potential in humans is merely based on anecdotal case reports, the current study aimed to prospectively and objectively examine the auditory and vestibular function in patients implanted with a MoM hip prosthesis. Twenty patients (15 males and 5 females, aged between 33 and 65 years) implanted with a primary MoM hip prosthesis were matched for age, gender, and noise exposure to 20 non-implanted control subjects. Each participant was subjected to an extensive auditory (conventional and high-frequency pure tone audiometry, transient evoked and distortion product otoacoustic emissions [TEOAEs and DPOAEs], auditory brainstem responses [ABR]) and vestibular test battery (cervical and ocular vestibular evoked myogenic potentials [cVEMPs and oVEMPs], rotatory test, caloric test, video head impulse test [vHIT]), supplemented with a blood s le collection to determine the plasma Co concentration. The median [interquartile range] plasma Co concentration was 1.40 [0.70, 6.30] µg/L in the MoM patient group and 0.19 [0.09, 0.34] µg/L in the control group. Within the auditory test battery, a clear trend was observed toward higher audiometric thresholds (11.2 to 16 kHz), lower DPOAE (between 4 and 8 kHz), and total TEOAE (1 to 4 kHz) litudes, and a higher interaural latency difference for wave V of the ABR in the patient versus control group (0.01 ≤ p 0.05). Within the vestibular test battery, considerably longer cVEMP P1 latencies, higher oVEMP litudes (0.01 ≤ p 0.05), and lower asymmetry ratio of the vHIT gain ( p 0.01) were found in the MoM patients. In the patient group, no suggestive association was observed between the plasma Co level and the auditory or vestibular outcome parameters. The auditory results seem to reflect signs of Co-induced damage to the hearing function in the high frequencies. This corresponds to previous findings on drug-induced ototoxicity and the recent animal experiments with Co, which identified the basal cochlear outer hair cells as primary targets and indicated that the cellular mechanisms underlying the toxicity might be similar. The vestibular outcomes of the current study are inconclusive and require further elaboration, especially with respect to animal studies. The lack of a clear dose–response relationship may question the clinical relevance of our results, but recent findings in MoM hip implant patients have confirmed that this relationship can be complicated by many patient-specific factors.
GABA mediates presynaptic inhibition at glycinergic synapses in a rat auditory brainstem nucleus
Publisher: Wiley
Date: 06-2000
DOI: 10.1111/J.1469-7793.2000.T01-1-00447.X
Abstract: Many inhibitory nerve terminals in the mammalian anteroventral cochlear nucleus (AVCN) contain both glycine and GABA, but the reason for the co-localization of these two inhibitory neurotransmitters in the AVCN is unknown. We have investigated the roles of glycine and GABA at synapses on bushy cells in the rat AVCN, using receptor immunohistochemistry and electrophysiology. Our immunohistochemical results show prominent punctate labelling of postsynaptic clusters of glycine receptors and of the receptor clustering protein gephyrin over the surface of bushy cells. In contrast, weak diffuse membrane immunolabelling of GABAA receptors was observed. Whole-cell recordings from bushy cells in AVCN slices demonstrated that evoked inhibitory postsynaptic currents (IPSCs) were predominantly (81 %) glycinergic, based on the decrease in litude of the IPSCs in bicuculline (10 microM). This observation was supported by the effect of strychnine (1 microM), which was to decrease the evoked IPSC (to 10 % of control IPSC litude) and to produce a greater than 90 % block of spontaneous miniature IPSCs. These results suggest a minor role for postsynaptic GABAA receptors in bushy cells, despite a high proportion of GABA-containing terminals on these cells. Therefore, a role for metabotropic GABAB receptors was investigated. Activation of GABAB receptors with baclofen revealed a significant attenuation of evoked glycinergic IPSCs. The effect of baclofen was presynaptic, as indicated by a lack of change in the mean litude of spontaneous IPSCs. Significantly, the decrease in the litude of evoked glycinergic IPSCs observed following repetitive nerve stimulation was reduced in the presence of the GABAB antagonist, CGP 35348. This indicates that synaptically released GABA can activate presynaptic GABAB receptors to reduce transmitter release at glycinergic synapses. Our results suggest specific pre- versus postsynaptic physiological roles for GABA and glycine in the AVCN.
Differentiation of Sensory Neuron Lineage During the Late First and Early Second Trimesters of Human Foetal Development
Publisher: Elsevier BV
Date: 07-2021
Altered neurofilament protein expression in the lateral vestibular nucleus in Parkinson’s disease
Publisher: Springer Science and Business Media LLC
Date: 19-09-2017
DOI: 10.1007/S00221-017-5092-3
Abstract: A major cause of morbidity in Parkinson's disease (PD) is postural instability. The neuropathology underlying postural instability is unknown. Postural control is mediated by Deiters' neurons of the lateral vestibular nucleus (LVN), which are the brainstem origin of descending vestibulospinal reflexes. Deiters' neurons express the cytostructural protein, non-phosphorylated neurofilament protein (NPNFP). In PD, reduced expression of NPNFP in substantia nigra (SN) neurons is believed to contribute to dysfunction. It was the aim of this study to determine if there is altered expression of NPNFP in the LVN in PD. We immunolabeled NPNFP in brainstem sections of six aged controls (mean age 92 yo) and six PD donors (mean age 83 yo). Our results show there was a ~ 50% reduction in NPNFP-positive Deiters' neurons compared to controls (13 ± 2.0/section vs 25.7 ± 3.0/section p < 0.01, repeated measures ANOVA). In contrast, there was no difference in NPNFP-positive counts in the facial nucleus between control and PD. The normalized intensity of NPNFP labeling in LVN was also reduced in PD (0.87 ± 0.05 vs 1.09 ± 0.03 p < 0.01). There was a 35% concurrent reduction in NPNFP-positive neuropil in PD relative to controls (p < 0.01). We also show there was an 84% increase (p < 0.05) in somatic lipofuscin in PD patients compared to control. Lipofuscin aggregation has been shown to increase not only with age but also with neurodegeneration. Furthermore, decreased NPNFP intensity was strongly correlated with increasing lipofuscin autofluorescence across all cases (R
The Long and Winding Road—Vestibular Efferent Anatomy in Mice
Publisher: Frontiers Media SA
Date: 28-01-2022
DOI: 10.3389/FNCIR.2021.751850
Abstract: The precise functional role of the Efferent Vestibular System (EVS) is still unclear, but the auditory olivocochlear efferent system has served as a reasonable model on the effects of a cholinergic and peptidergic input on inner ear organs. However, it is important to appreciate the similarities and differences in the structure of the two efferent systems, especially within the same animal model. Here, we examine the anatomy of the mouse EVS, from its central origin in the Efferent Vestibular Nucleus (EVN) of the brainstem, to its peripheral terminations in the vestibular organs, and we compare these findings to known mouse olivocochlear anatomy. Using transgenic mouse lines and two different tracing strategies, we examine central and peripheral anatomical patterning, as well as the anatomical pathway of EVS axons as they leave the mouse brainstem. We separately tag the left and right efferent vestibular nuclei (EVN) using Cre-dependent, adeno-associated virus (AAV)-mediated expression of fluorescent reporters to map their central trajectory and their peripheral terminal fields. We couple this with Fluro-Gold retrograde labeling to quantify the proportion of ipsi- and contralaterally projecting cholinergic efferent neurons. As in some other mammals, the mouse EVN comprises one group of neurons located dorsal to the facial genu, close to the vestibular nuclei complex (VNC). There is an average of just 53 EVN neurons with rich dendritic arborizations towards the VNC. The majority of EVN neurons, 55%, project to the contralateral eighth nerve, crossing the midline rostral to the EVN, and 32% project to the ipsilateral eighth nerve. The vestibular organs, therefore, receive bilateral EVN innervation, but without the distinctive zonal innervation patterns suggested in gerbil. Similar to gerbil, however, our data also suggest that in idual EVN neurons do not project bilaterally in mice. Taken together, these data provide a detailed map of EVN neurons from the brainstem to the periphery and strong anatomical support for a dominant contralateral efferent innervation in mammals.
Relating nanoscale structure to optoelectronic functionality in multiphase donor–acceptor nanoparticles for printed electronics applications
Publisher: Springer Science and Business Media LLC
Date: 12-2020
DOI: 10.1557/MRC.2020.76
Theory of mind and mental state discourse during book reading and story‐telling tasks
Publisher: Wiley
Date: 03-2005
Developmental changes in EPSC quantal size and quantal content at a central glutamatergic synapse in rat
Publisher: Wiley
Date: 09-1998
DOI: 10.1111/J.1469-7793.1998.861BG.X
Abstract: 1. Developmental changes in litude and time course of single-fibre-evoked and spontaneous EPSCs mediated by AMPA and NMDA receptors at the endbulb-bushy cell synapse of rats from 4 to 22 days of age were recorded using whole-cell patch-cl methods in in vitro slices of cochlear nucleus. 2. The mean conductance of the AMPA component of evoked EPSCs increased by 66 %, while that of the NMDA component decreased by 61 %, for 12- to 18-day-old rats cf. 4- to 11-day-old rats. 3. The mean AMPA spontaneous EPSC conductance increased by 54 %, while mean NMDA spontaneous EPSC conductance decreased by 83 %, for 12- to 22-day-old rats cf. 4- to 11-day-old rats. The mean number of quanta contributing to peak evoked AMPA conductance also increased by 78 % in the older age group, after correction for the asynchrony of evoked quantal release. 4. The decay time constant of spontaneous AMPA EPSCs showed a small decrease in older animals, while the decay time constant of spontaneous NMDA EPSCs was markedly decreased in older animals. The decay time constants of evoked NMDA EPSCs showed a quantitatively similar decrease to that of spontaneous NMDA EPSCs. This suggests that AMPA receptor subunit composition is unlikely to undergo developmental change, while NMDA receptor subunit composition may be substantially altered during synaptic maturation. 5. These data are consistent with a developmentally increased efficacy of AMPA receptor-mediated synaptic transmission at the endbulb-bushy cell synapse, due to an increase in underlying AMPA-mediated quantal size and content during the same period as a transient co-localization of NMDA receptors.
ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells
Publisher: American Physiological Society
Date: 2018
Abstract: In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 −/− ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 −/− mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted efferent mechanism for altering hair cell membrane potential and decreasing membrane resistance that should reduce sensitivity to hair bundle displacements.
Vestibular Adaptation and Compensation
Publisher: Springer New York
Date: 2015
Central Vestibular Signal Processing
Publisher: Springer New York
Date: 2015
Heterogeneous responses to antioxidants in noradrenergic neurons of the Locus coeruleus indicate differing susceptibility to free radical content
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/820285
Abstract: The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current cl experiments, most neurons (55% 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27% 3/11) or depolarization and increased firing rate (18% 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca 2+ concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca 2+ -dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson’s disease. If this is the case, there may be a protective role for antioxidant therapies.
Development and characterization of human fetal female reproductive tract organoids to understand Müllerian duct anomalies
Publisher: Proceedings of the National Academy of Sciences
Date: 18-07-2022
Abstract: Müllerian ducts are paired tubular structures that give rise to most of the female reproductive organs. Any abnormalities in the development and differentiation of these ducts lead to anatomical defects in the female reproductive tract organs categorized as Müllerian duct anomalies. Due to the limited access to fetal tissues, little is understood of human reproductive tract development and the associated anomalies. Although organoids represent a powerful model to decipher human development and disease, such organoids from fetal reproductive organs are not available. Here, we developed organoids from human fetal fallopian tubes and uteri and compared them with their adult counterparts. Our results demonstrate that human fetal reproductive tract epithelia do not express some of the typical markers of adult reproductive tract epithelia. Furthermore, fetal organoids are grossly, histologically, and proteomically different from adult organoids. While external supplementation of WNT ligands or activators in culture medium is an absolute requirement for the adult reproductive tract organoids, fetal organoids are able to grow in WNT-deficient conditions. We also developed decellularized tissue scaffolds from adult human fallopian tubes and uteri. Transplantation of fetal organoids onto these scaffolds led to the regeneration of the adult fallopian tube and uterine epithelia. Importantly, suppression of Wnt signaling, which is altered in patients with Müllerian duct anomalies, inhibits the regenerative ability of human fetal organoids and causes severe anatomical defects in the mouse reproductive tract. Thus, our fetal organoids represent an important platform to study the underlying basis of human female reproductive tract development and diseases.
Organic Semiconductors for Optically Triggered Neural Interfacing: The Impact of Device Architecture in Determining Response Magnitude and Polarity
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 07-2021
A review of mechanical and synaptic processes in otolith transduction of sound and vibration for clinical VEMP testing
Publisher: American Physiological Society
Date: 07-2018
Abstract: Older studies of mammalian otolith physiology have focused mainly on sustained responses to low-frequency ( Hz) or maintained linear acceleration. So the otoliths have been regarded as accelerometers. Thus evidence of otolithic activation and high-precision phase locking to high-frequency sound and vibration appears to be very unusual. However, those results are exactly in accord with a substantial body of knowledge of otolith function in fish and frogs. It is likely that phase locking of otolith afferents to vibration is a general property of all vertebrates. This review examines the literature about the activation and phase locking of single otolithic neurons to air-conducted sound and bone-conducted vibration, in particular the high precision of phase locking shown by mammalian irregular afferents that synapse on striolar type I hair cells by calyx endings. Potassium in the synaptic cleft between the type I hair cell receptor and the calyx afferent ending may be responsible for the tight phase locking of these afferents even at very high discharge rates. Since frogs and fish do not possess full calyx endings, it is unlikely that they show phase locking with such high precision and to such high frequencies as has been found in mammals. The high-frequency responses have been modeled as the otoliths operating in a seismometer mode rather than an accelerometer mode. These high-frequency otolithic responses constitute the neural basis for clinical vestibular-evoked myogenic potential tests of otolith function.
Preliminary characterization of voltage-activated whole-cell currents in developing human vestibular hair cells and calyx afferent terminals
Publisher: Springer Science and Business Media LLC
Date: 19-06-2014
Potassium accumulation between type I hair cells and calyx terminals in mouse crista
Publisher: Springer Science and Business Media LLC
Date: 25-02-2011
DOI: 10.1007/S00221-011-2592-4
Abstract: The mode of synaptic transmission in the vestibular periphery, between type I hair cells and their associated calyx terminal, has been the subject of much debate. The close and extensive apposition of pre- and post-synaptic elements has led some to suggest potassium (K(+)) accumulates in the intercellular space and even plays a role in synaptic transmission. During patch cl recordings from isolated and embedded hair cells in a semi-intact preparation of the mouse cristae, we noted marked differences in whole-cell currents. Embedded type I hair cells show a prominent droop during steady-state activation as well as a dramatic collapse in tail currents. Responses to a depolarizing voltage step (-124 to +16 mV) in embedded, but not isolated, hair cells resulted in a >40 mV shift of the K(+) equilibrium potential and a rise in effective K(+) concentration (>50 mM) in the intercellular space. Together these data suggest K(+) accumulation in the intercellular space accounts for the different responses in isolated and embedded type I hair cells. To test this notion, we exposed the preparation to hyperosmotic solutions to enlarge the intercellular space. As predicted, the K(+) accumulation effects were reduced however, a fit of our data with a classic diffusion model suggested K(+) permeability, rather than the intercellular space, had been altered by the hyperosmotic change. These results support the notion that under depolarizing conditions substantial K(+) accumulation occurs in the space between type I hair cells and calyx. The extent of K(+) accumulation during normal synaptic transmission, however, remains to be determined.
Organic bioelectronics: Materials and biocompatibility
Publisher: MDPI AG
Date: 13-08-2018
DOI: 10.3390/IJMS19082382
Abstract: Organic electronic materials have been considered for a wide-range of technological applications. More recently these organic (semi)conductors (encompassing both conducting and semi-conducting organic electronic materials) have received increasing attention as materials for bioelectronic applications. Biological tissues typically comprise soft, elastic, carbon-based macromolecules and polymers, and communication in these biological systems is usually mediated via mixed electronic and ionic conduction. In contrast to hard inorganic semiconductors, whose primary charge carriers are electrons and holes, organic (semi)conductors uniquely match the mechanical and conduction properties of biotic tissue. Here, we review the biocompatibility of organic electronic materials and their implementation in bioelectronic applications.
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