Alan Brichta

Vestibulo-Ocular Reflex Short-Term Adaptation Is Halved After Compensation for Unilateral Labyrinthectomy

Publisher: Springer Science and Business Media LLC

Date: 21-03-2022

DOI: 10.1007/S10162-022-00844-4

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.

Properties of Deiters’ neurons and inhibitory synaptic transmission in the mouse lateral vestibular nucleus

Publisher: American Physiological Society

Date: 07-2022

DOI: 10.1152/JN.00016.2022

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.

Evidence for a Critical Period in the Development of Excitability and Potassium Currents in Mouse Lumbar Superficial Dorsal Horn Neurons

Publisher: American Physiological Society

Date: 04-2009

DOI: 10.1152/JN.90755.2008

Abstract: The output of superficial dorsal horn (SDH laminae I–II) neurons is critical for processing nociceptive, thermal, and tactile information. Like other neurons, the combined effects of synaptic inputs and intrinsic membrane properties determine their output. It is well established that peripheral synaptic inputs to SDH neurons undergo extensive reorganization during pre- and postnatal development. It is unclear, however, how membrane properties or the subthreshold whole cell currents that shape SDH neuron output change during this period. Here we assess the intrinsic membrane properties and whole cell currents in mouse SDH neurons during late embryonic and early postnatal development (E15–P25). Transverse slices were prepared from lumbar spinal cord and whole cell recordings were obtained at 32°C. During this developmental period resting membrane potential (RMP) became more hyperpolarized (by ∼10 mV, E15–E17 vs. P21–P25) and input resistance decreased (1,074 ± 78 vs. 420 ± 27 MΩ). In addition, action potential (AP) litude and AP afterhyperpolarization increased, whereas AP half-width decreased. Before and after birth (E15–P10), AP discharge evoked by intracellular current injection was limited to a single AP at depolarization onset in many neurons ( %). In older animals (P11–P25) this changed, with AP discharge consisting of brief bursts at current onset (∼46% of neurons). Investigation of major subthreshold whole cell currents showed the rapid A-type potassium current ( I Ar ) dominated at all ages examined (90% of neurons at E15–E17, decreasing to % after P10). I Ar expression levels, based on peak current litude, increased during development. Steady-state inactivation and activation for I Ar were slightly less potent in E15–E17 versus P21–P25 neurons at potentials near RMP (−55 mV). Together, our data indicate that intrinsic properties and I Ar expression change dramatically in SDH neurons during development, with the greatest alterations occurring on either side of a critical period, P6–P10.

A horizontal slice preparation for examining the functional connectivity of dorsal column fibres in mouse spinal cord

Publisher: Elsevier BV

Date: 09-2011

DOI: 10.1016/J.JNEUMETH.2011.06.017

Abstract: In spinal cord injury (SCI) research, axon regeneration across spinal lesions is most often assessed using anatomical methods. It would be extremely advantageous, however, to examine the functional synaptic connectivity of regenerating fibres, using high-resolution electrophysiological methods. We have therefore developed a mouse horizontal spinal cord slice preparation that permits detailed analysis of evoked dorsal column (DCol) synaptic inputs on spinal neurons, using whole-cell patch cl electrophysiology. This preparation allows us to characterise postsynaptic currents and potentials in response to electrical stimulation of DCol fibres, along with the intrinsic properties of spinal neurons. In addition, we demonstrate that low magnification calcium imaging can be used effectively to survey the spread of excitation from DCol stimulation in horizontal slices. This preparation is a potentially valuable tool for SCI research where confirmation of regenerated, functional synapses across a spinal lesion is critical.

Moving From an Averaged to Specific View of Spinal Cord Pain Processing Circuits

Publisher: American Physiological Society

Date: 09-2007

DOI: 10.1152/JN.00581.2007

Abstract: Neurons in the superficial dorsal horn (SDH) of the spinal cord play a critical role in processing potentially painful or noxious signals from skin, muscle, and viscera. Many acute pain therapies are based on the notion that altering the excitability of SDH neurons can block or gate these signals and reduce pain. This same notion also underlies treatments for certain chronic pain states. Basic scientists are now beginning to identify a number of potential molecular targets for spinal cord–based pain therapies with a focus on ion channels and receptors that can alter neuronal excitability. The current challenge in pain research is to identify which are the most promising targets and how their manipulation alters pain processing. In this review, we propose that our understanding of spinal pain processing mechanisms and translation of these discoveries into pain therapies could be improved by 1) better appreciating and understanding neuronal heterogeneity in the SDH 2) establishing connectivity patterns among SDH neuron types and 3) testing and extending findings made in vitro to intact (in vivo) animal models. As this information becomes available, it will be possible to determine the precise distribution of potential therapeutic targets on various SDH neuron types within specific circuits known to be functionally important in spinal pain processing.

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 .

An in vivo mouse spinal cord preparation for patch-clamp analysis of nociceptive processing

Publisher: Elsevier BV

Date: 07-2004

DOI: 10.1016/J.JNEUMETH.2004.01.014

Effects of Ageing on the Mitochondrial Genome in Rat Vestibular Organs

Publisher: Bentham Science Publishers Ltd.

Date: 07-02-2019

DOI: 10.2174/1874609811666180830143358

Electrical maturation of spinal neurons in the human fetus: Comparison of ventral and dorsal horn

Publisher: American Physiological Society

Date: 11-2015

DOI: 10.1152/JN.00682.2015

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.

Recording Temperature Affects the Excitability of Mouse Superficial Dorsal Horn Neurons, In Vitro

Publisher: American Physiological Society

Date: 05-2008

DOI: 10.1152/JN.01176.2007

Abstract: Superficial dorsal horn (SDH) neurons in laminae I–II of the spinal cord play an important role in processing noxious stimuli. These neurons represent a heterogeneous population and are ided into various categories according to their action potential (AP) discharge during depolarizing current injection. We recently developed an in vivo mouse preparation to examine functional aspects of nociceptive processing and AP discharge in SDH neurons and to extend investigation of pain mechanisms to the genetic level of analysis. Not surprisingly, some in vivo data obtained at body temperature (37°C) differed from those generated at room temperature (22°C) in spinal cord slices. In the current study we examine how temperature influences SDH neuron properties by making recordings at 22 and 32°C in transverse spinal cord slices prepared from L3–L5 segments of adult mice (C57Bl/6). Patch-cl recordings (KCH 3 SO 4 internal) were made from visualized SDH neurons. At elevated temperature all SDH neurons had reduced input resistance and smaller, briefer APs. Resting membrane potential and AP afterhyperpolarization litude were temperature sensitive only in subsets of the SDH population. Notably, elevated temperature increased the prevalence of neurons that did not discharge APs during current injection. These reluctant firing neurons expressed a rapid A-type potassium current, which is enhanced at higher temperatures and thus restrains AP discharge. When compared with previously published whole cell recordings obtained in vivo (37°C) our results suggest that, on balance, in vitro data collected at elevated temperature more closely resemble data collected under in vivo conditions.

Are all spinal segments equal: intrinsic membrane properties of superficial dorsal horn neurons in the developing and mature mouse spinal cord

Publisher: Wiley

Date: 14-03-2012

DOI: 10.1113/JPHYSIOL.2012.227389

Cervix Stimulation Evokes Predominantly Subthreshold Synaptic Responses in Mouse Thoracolumbar and Lumbosacral Superficial Dorsal Horn Neurons

Publisher: Oxford University Press (OUP)

Date: 06-2010

DOI: 10.1111/J.1743-6109.2010.01768.X

Abstract: Sensory input from the female reproductive tract (FRT) plays a pivotal role in coordinating reproductive reflexes. Additionally, a number of disorders, especially chronic pelvic pain, may be due to disturbances in sensory processing of signals from the FRT. Our aim was to record synaptic responses in neurons from lumbar and sacral spinal cord segments during mechanical stimulation of the cervix. We developed an in vivo preparation of the mouse spinal cord to record synaptic potentials from superficial dorsal horn (SDH) neurons under whole-cell patch cl recording conditions. We analyzed the strength and distribution of excitatory postsynaptic potentials in SDH neurons evoked during mechanical stimulation of the cervix and cutaneous sites. Resting membrane potential and neuronal input resistance was similar in thoracolumbar (TL, T13-L3) and lumbosacral (LS, L6-S2) segments. We elicited activity in 6/21 TL neurons and 15/39 LS neurons using mechanical stimulation of the cervix with a blunt probe. The majority of these neurons responded to cervix stimulation with bursts of subthreshold excitatory postsynaptic potentials (4/6 and 12/15 TL and LS neurons, respectively). The remainder responded with sufficient magnitude to generate action potentials (2/6 and 3/15 TL and LS neurons). Cutaneous synaptic inputs were also elicited in 11/21 TL neurons following stimulation of the flank/leg, 19/39 LS neurons by stimulation of the tail, and three LS neurons by perineal stimulation. Some neurons received convergent synaptic inputs from the cervix and cutaneous sites (4/6 TL and 4/15 LS). These data demonstrate that spinal projections of cervix afferents are widely dispersed in the SDH and considerable convergence exists between neurons innervating the cervix and cutaneous structures. Our results indicate that much of the synaptic activity evoked in SDH neurons following cervix stimulation is subthreshold.

An increase in glycinergic quantal amplitude and frequency during early vestibular compensation in mouse

Publisher: American Physiological Society

Date: 2010

DOI: 10.1152/JN.91223.2008

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.

Pioneers in CNS inhibition: 2. Charles Sherrington and John Eccles on inhibition in spinal and supraspinal structures

Publisher: Elsevier BV

Date: 05-2020

DOI: 10.1016/J.BRAINRES.2019.146540

Abstract: This article reviews the contributions of the English neurophysiologist, Charles Scott Sherrington [1857-1952], and his Australian PhD trainee and collaborator, John Carew Eccles [1903-1997], to the concept of central inhibition in the spinal cord and brain. Both were awarded Nobel Prizes Sherrington in 1932 for "discoveries regarding the function of neurons," and Eccles in 1963 for "discoveries concerning the ionic mechanisms involved in excitation and inhibition in central portions of the nerve cell membrane." Both spoke about central inhibition at their Nobel Prize Award Ceremonies. The subsequent publications of their talks were entitled "Inhibition as a coordinative factor" and "The ionic mechanism of postsynaptic inhibition", respectively. Sherrington's work on central inhibition spanned 41 years (1893-1934), and for Eccles 49 years (1928-1977). Sherrington first studied central inhibition by observing hind limb muscle responses to electrical (peripheral nerve) and mechanical (muscle) stimulation. He used muscle length and force measurements until the early 1900s and electromyography in the late 1920s. Eccles used these techniques while working with Sherrington, but later employed extracellular microelectrode recording in the spinal cord followed in 1951 by intracellular recording from spinal motoneurons. This considerably advanced our understanding of central inhibition. Sherrington's health was poor during his retirement years but he nonetheless made a small number of largely humanities contributions up to 1951, one year before his death at the age of 94. In contrast, Eccles retained his health and vigor until 3 years before his death and published prolifically on many subjects during his 22 years of official retirement. His last neuroscience article appeared in 1994 when he was 91. Despite poor health he continued thinking about his life-long interest, the mind-brain problem, and was attempting to complete his autobiography in the last years of his life.

In vivo responses of mouse superficial dorsal horn neurones to both current injection and peripheral cutaneous stimulation

Publisher: Wiley

Date: 12-2004

DOI: 10.1113/JPHYSIOL.2004.072645

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.

Vestibular System

Publisher: Elsevier

Date: 2012

DOI: 10.1016/B978-0-12-369497-3.10027-5

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

DOI: 10.1021/ACSABM.1C00581

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

DOI: 10.1152/JN.00110.2016

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 Once-Daily High Dose of Intraperitoneal Ascorbate Improves Vestibulo-ocular Reflex Compensation After Unilateral Labyrinthectomy in the Mouse

Publisher: Springer Science and Business Media LLC

Date: 03-01-2022

DOI: 10.1007/S10162-021-00831-1

A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications

Publisher: American Physiological Society

Date: 02-2020

DOI: 10.1152/JN.00053.2019

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.

Using indirect inference to identify models of vestibular nerve response in an isolated inner ear

Publisher: IEEE

Date: 11-2017

DOI: 10.1109/AUCC.2016.7867925

A Neuroethics Framework for the Australian Brain Initiative

Publisher: Elsevier BV

Date: 02-2019

DOI: 10.1016/J.NEURON.2019.01.004

Abstract: Neuroethics is central to the Australian Brain Initiative's aim to sustain a thriving and responsible neurotechnology industry. Diverse and inclusive community and stakeholder engagement and a trans-disciplinary approach to neuroethics will be key to the success of the Australian Brain Initiative.

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

Erratum: A Neuroethics Framework for the Australian Brain Initiative (Neuron (2019) 101(3) (365–369), (S0896627319300054), (10.1016/j.neuron.2019.01.004))

Publisher: Elsevier BV

Date: 2020

DOI: 10.1016/J.NEURON.2019.12.019

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.

ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells

Publisher: American Physiological Society

Date: 2018

DOI: 10.1152/JN.00030.2017

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.

Pinch‐current injection defines two discharge profiles in mouse superficial dorsal horn neurones, in vitro

Publisher: Wiley

Date: 26-01-2007

DOI: 10.1113/JPHYSIOL.2006.123349

Pre-employment hearing threshold levels of 59,601 Australian male coal miners compared to an otologically normal international male population (ISO7029:2019)

Publisher: Informa UK Limited

Date: 08-07-2022

DOI: 10.1080/14992027.2022.2088625

Abstract: This study compared the pre-employment median hearing threshold level (HTL) distribution from a population of coal miners from New South Wales (NSW), Australia, to an otologically normal, age-matched population described by the International Standards Organisation (ISO) ISO 7029:2019, to determine any differences. This was an observational, retrospective, repeated cross-sectional study. De-identified audiometric records of 59,601 male employees entering NSW coal mining in three representative five-year periods between 1991 and 2015 were utilised. The median HTL deviation of the mining population was statistically significantly different ( These findings indicate that some NSW coal mine workers commence their careers with evidence of pre-existing hearing loss (HL), in an industry with excessive noise exposures. These results provide Australian mining and other noisy industries with evidence to support a review of hearing conservation strategies to improve mitigation of hearing loss across the working lifespan.

Degradation of nano-ZnO particles filled styrene-based and epoxy-based SMPs under UVA exposure

Publisher: Elsevier BV

Date: 11-2015

DOI: 10.1016/J.COMPSTRUCT.2015.07.023

Altered potassium channel function in the superficial dorsal horn of thespasticmouse

Publisher: Wiley

Date: 28-09-2007

DOI: 10.1113/JPHYSIOL.2007.138198

Alpha-9 nicotinic acetylcholine receptors mediate hypothermic responses elicited by provocative motion in mice

Publisher: Elsevier BV

Date: 05-2017

DOI: 10.1016/J.PHYSBEH.2017.03.012

Abstract: Hypothermic responses accompany motion sickness in humans and can be elicited by provocative motion in rats. We aimed to determine the potential role in these responses of the efferent cholinergic vestibular innervation. To this end, we used knockout (KO) mice lacking α9 cholinoreceptor subunit predominantly expressed in the vestibular hair cells and CBA strain as a wild-type (WT) control. In WT mice, circular horizontal motion (1Hz, 4cm radius, 20min) caused rapid and dramatic falls in core body temperature and surface head temperature associated with a transient rise in the tail temperature these responses were substantially attenuated in KO mice changes were (WT vs. KO): for the core body temperature-5.2±0.3 vs. -2.9±0.3°C for the head skin temperature-3.3±0.2 vs. -1.7±0.2°C for the tail skin temperature+3.9±1.1 vs+1.1±1.2°C. There was a close correlation in the time course of cooling the body and the surface of the head. KO mice also required 25% more time to complete a balance test. We conclude: i) that the integrity of cholinergic efferent vestibular system is essential for the full expression of motion-induced hypothermia in mice, and that the role of this system is likely facilitatory ii) that the system is involvement in control of balance, but the involvement is not major iii) that in mice, motion-induced body cooling is mediated via increased heat flow through vasodilated tail vasculature and (likely) via reduced thermogenesis. Our results support the idea that hypothermia is a biological correlate of a nausea-like state in animals.

Alteration of miRNA-mRNA interactions in lymphocytes of individuals with schizophrenia

Publisher: Elsevier BV

Date: 05-2019

DOI: 10.1016/J.JPSYCHIRES.2019.02.023

Abstract: The aetiology of schizophrenia is complex, heterogeneous, and involves interplay of many genetic and environmental influences. While significant progress has been made in the understanding the common heritable component, we are still grappling with the genomic encoding of environmental risk. One class of molecule that has tremendous potential is miRNA. These molecules are regulated by genetic and environmental factors associated with schizophrenia and have a very significant impact on temporospatial patterns of gene expression. To better understand the relationship between miRNA and gene expression in the disorder we analysed these molecules in RNA isolated from peripheral blood mononuclear cells (PBMCs) obtained from an Australian cohort of 36 in iduals with schizophrenia and 15 healthy controls using next-generation RNA sequencing. Significant changes in both mRNA and miRNA expression profiles were observed implicating important interaction networks involved in immune activity and development. We also observed sexual dimorphism, particularly in relation to variation in mRNA, with males showing significantly more differentially expressed genes. Interestingly, while we explored expression in lymphocytes, the systems biology of miRNA-mRNA interactions was suggestive of significant pleiotropy with enrichment of networks related to neuronal activity.

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.

Hearing threshold levels of Australian coal mine workers: a retrospective cross-sectional study of 64196 audiograms

Publisher: Informa UK Limited

Date: 22-02-2021

DOI: 10.1080/14992027.2021.1884908

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

DOI: 10.1109/JSTQE.2021.3051408

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

DOI: 10.1152/JN.00031.2019

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

DOI: 10.1007/S10162-014-0471-Y

Different forms of glycine- and GABA A-receptor mediated inhibitory synaptic transmission in mouse superficial and deep dorsal horn neurons

Publisher: SAGE Publications

Date: 2009

DOI: 10.1186/1744-8069-5-65

Abstract: Neurons in superficial (SDH) and deep (DDH) laminae of the spinal cord dorsal horn receive sensory information from skin, muscle, joints and viscera. In both regions, glycine-(GlyR) and GABA A -receptors (GABA A Rs) contribute to fast synaptic inhibition. For rat, several types of GABA A R coexist in the two regions and each receptor type provides different contributions to inhibitory tone. Recent work in mouse has discovered an additional type of GlyR, (containing alpha 3 subunits) in the SDH. The contribution of differing forms of the GlyR to sensory processing in SDH and DDH is not understood. Here we compare fast inhibitory synaptic transmission in mouse (P17-37) SDH and DDH using patch-cl electrophysiology in transverse spinal cord slices (L3-L5 segments, 23°C). GlyR-mediated mIPSCs were detected in 74% (25/34) and 94% (25/27) of SDH and DDH neurons, respectively. In contrast, GABA A R-mediated mIPSCs were detected in virtually all neurons in both regions (93%, 14/15 and 100%, 18/18). Several Gly- and GABA A R properties also differed in SDH vs. DDH. GlyR-mediated mIPSC litude was smaller (37.1 ± 3.9 vs. 64.7 ± 5.0 pA n = 25 each), decay time was slower (8.5 ± 0.8 vs. 5.5 ± 0.3 ms), and frequency was lower (0.15 ± 0.03 vs. 0.72 ± 0.13 Hz) in SDH vs. DDH neurons. In contrast, GABA A R-mediated mIPSCs had similar litudes (25.6 ± 2.4, n = 14 vs. 25. ± 2.0 pA, n = 18) and frequencies (0.21 ± 0.08 vs. 0.18 ± 0.04 Hz) in both regions however, decay times were slower (23.0 ± 3.2 vs. 18.9 ± 1.8 ms) in SDH neurons. Mean single channel conductance underlying mIPSCs was identical for GlyRs (54.3 ± 1.6 pS, n = 11 vs. 55.7 ± 1.8, n = 8) and GABA A Rs (22.7 ± 1.7 pS, n = 10 vs. 22.4 ± 2.0 pS, n = 11) in both regions. We also tested whether the synthetic endocanabinoid, methandamide (methAEA), had direct effects on Gly- and GABA A Rs in each spinal cord region. MethAEA (5 μM) reduced GlyR-mediated mIPSC frequency in SDH and DDH, but did not affect other properties. Similar results were observed for GABA A R mediated mIPSCs, however, rise time was slowed by methAEA in SDH neurons. Together these data show that Gly- and GABA A Rs with clearly differing physiological properties and cannabinoid-sensitivity contribute to fast synaptic inhibition in mouse SDH and DDH.

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.

Crosstalk between mitochondria, calcium channels and actin cytoskeleton modulates noradrenergic activity of locus coeruleus neurons

Publisher: Wiley

Date: 02-04-2019

DOI: 10.1111/JNC.14692

Abstract: Locus coeruleus (LC) is the name of a group of large sized neurons located at the brain stem, which provides the main source of noradrenaline to the central nervous system, virtually, innervating the whole brain. All noradrenergic signalling provided by this nucleus is dependent on an intrinsic pacemaker process. Our study aims to understand how noradrenergic neurons finely tune their pacemaker processes and regulate their activities. Here we present that mitochondrial perturbation in the LC from mice, inhibits spontaneous firing by a hyperpolarizing response that involves Ca

Estimating the Membrane Properties of Vestibular Type II Hair Cells using Continuous-time System Identification

Publisher: Elsevier BV

Date: 2020

DOI: 10.1016/J.IFACOL.2020.12.477

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.

Harbin Institute Of Technology

Location: China

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Hainan University

Location: China

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Discovery Projects - Grant ID: DP0556478

Start Date: 2005

End Date: 03-2008

Amount: $220,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE220100168

Start Date: 11-2022

End Date: 11-2024

Amount: $420,347.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP230102705

Start Date: 02-2023

End Date: 01-2026

Amount: $463,985.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989861

Start Date: 2009

End Date: 12-2010

Amount: $650,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0211014

Start Date: 2001

End Date: 12-2002

Amount: $337,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100008

Start Date: 2010

End Date: 12-2010

Amount: $350,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100012

Start Date: 2018

End Date: 12-2018

Amount: $414,570.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453630

Start Date: 2004

End Date: 12-2004

Amount: $274,692.00

Funder: Australian Research Council