Compound Action Potential Recordings Research Articles

A Guinea Pig Model of Selective Severe High-Frequency Hearing Loss

Using an appropriate dose of an aminoglycoside antibiotic cotreated with a loop diuretic a guinea pig model of high-frequency loss can be obtained mimicking cochlear implant candidates with low-frequency residual hearing. We examined the stability of this model over time. A well-established method to create an animal model for profound deafness is cotreatment with an aminoglycoside antibiotic and a loop diuretic. Recent data indicated that reduction of the aminoglycoside dose might yield selective high-frequency hearing loss. Such a model is relevant for studies related to hybrid cochlear implant devices, for example, with respect to preservation of residual hearing. Guinea pigs received an electrode for chronic recording of compound action potentials to tones to assess thresholds. They were treated with a coadministration of kanamycin (200 mg/kg) and furosemide (100 mg/kg), after which, the animals were sacrificed for histologic analysis at 2, 4, or 7 weeks. After 2 to 7 weeks threshold shifts were greater than 50 dB for 8 to 16 kHz in 15 of 17 animals, whereas threshold shifts at 2 kHz or lower were less than 50 dB in 13 animals. Major threshold shifts occurred the first 2 to 4 days; subsequently, some spontaneous recovery occurred and, after 2-3 weeks thresholds, remained stable. Inner hair cell loss still progressed between 2 and 4 weeks in the most basal cochlear region; thereafter, hair cell loss was stable. An appropriate animal model for selective severe high-frequency hearing loss was obtained, which is stable at 4 weeks after ototoxic treatment.

Feedback from Horizontal Cells to Cones Mediates Color Induction and May Facilitate Color Constancy in Rainbow Trout

Color vision is most beneficial when the visual system is color constant and can correct the excitations of photoreceptors for differences in environmental irradiance. A phenomenon related to color constancy is color induction, where the color of an object shifts away from the color of its surroundings. These two phenomena depend on chromatic spatial integration, which was suggested to originate at the feedback synapse from horizontal cells (HC) to cones. However, the exact retinal site was never determined. Using the electroretinogram and compound action potential recordings, we estimated the spectral sensitivity of the photoresponse of cones, the output of cones, and the optic nerve in rainbow trout. Recordings were performed before and following pharmacological inhibition of HC-cone feedback, and were repeated under two colored backgrounds to estimate the efficiency of color induction. No color induction could be detected in the photoresponse of cones. However, the efficiency of color induction in the cone output and optic nerve was substantial, with the efficiency in the optic nerve being significantly higher than in the cone output. We found that the efficiency of color induction in the cone output and optic nerve decreased significantly with the inhibition of HC-cone feedback. Therefore, our findings suggest not only that color induction originates as a result of HC-cone feedback, but also that this effect of HC-cone feedback is further amplified at downstream retinal elements, possibly through feedback mechanisms at the inner plexiform layer. This study provides evidence for an important role of HC-cone feedback in mediating color induction, and therefore, likely also in mediating color constancy.

TRPA1 and TRPV1 are differentially involved in heat nociception of mice

Two transient receptor potential (TRP) channels, TRPV1 and TRPA1, have been physiologically studied with regard to noxious heat transduction. Evidence argues against these channels as sole transducers of noxious heat or cold, respectively. Moreover, in submammalian species the TRPA1 orthologue shows heat sensitivity. In vitro, single-fibre and compound action potential recordings from C-fibres as well as measurements of stimulated cutaneous CGRP release are combined with behavioural experiments to assess heat responsiveness in wild type mice, TRPA1 and TRPV1 as well as double-null mutants. Heat thresholds of cutaneous C-mechano-heat sensitive fibres were significantly higher in TRPA1-/- (43 °C) than +/+ (40 °C) mice, and averaged heat responses were clearly weaker, whereas TRPV1-/- showed normal heat thresholds and responses (up to 46 °C). Compound action potential recordings revealed much less activity-dependent slowing of conduction velocity upon noxious heat stimulation in TRPA1-/- and a delayed deficit in TRPV1-/- in comparison to controls. Heat-induced calcitonin gene-related peptide release was reduced in TRPV1-/- but not TRPA1-/- animals. Paw withdrawal latencies to radiant heat were significantly elevated in TRPA1-/-, more so in TRPV1-/- animals. In general, double-null mutants were similar to TRPV1-/- except for the single-fibre heat responses which appeared as weak as in TRPA1-/-. Our results indicate that in addition to TRPV1, TRPA1 plays a role in heat nociception, in particular in definition of the heat threshold, and might therefore serve as a therapeutic target in acute inflammatory pain.

Antibodies to Gliomedin Cause Peripheral Demyelinating Neuropathy and the Dismantling of the Nodes of Ranvier

Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are conditions that affect peripheral nerves. The mechanisms that underlie demyelination in these neuropathies are unknown. Recently, we demonstrated that the node of Ranvier is the primary site of the immune attack in patients with GBS and CIDP. In particular, GBS patients have antibodies against gliomedin and neurofascin, two adhesion molecules that play a crucial role in the formation of nodes of Ranvier. We demonstrate that immunity toward gliomedin, but not neurofascin, induced a progressive neuropathy in Lewis rats characterized by conduction defects and demyelination in spinal nerves. The clinical symptoms closely followed the titers of anti-gliomedin IgG and were associated with an important deposition of IgG at nodes. Furthermore, passive transfer of antigliomedin IgG induced a severe demyelinating condition and conduction loss. In both active and passive models, the immune attack at nodes occasioned the loss of the nodal clusters for gliomedin, neurofascin-186, and voltage-gated sodium channels. These results indicate that primary immune reaction against gliomedin, a peripheral nervous system adhesion molecule, can be responsible for the initiation or progression of the demyelinating form of GBS. Furthermore, these autoantibodies affect saltatory propagation by dismantling nodal organization and sodium channel clusters. Antibodies reactive against nodal adhesion molecules thus likely participate in the pathologic process of GBS and CIDP.

Local Loperamide Injection Reduces Mechanosensitivity of Rat Cutaneous, Nociceptive C-Fibers

Loperamide reverses signs of mechanical hypersensitivity in an animal model of neuropathic pain suggesting that peripheral opioid receptors may be suitable targets for the treatment of neuropathic pain. Since little is known about loperamide effects on the responsiveness of primary afferent nerve fibers, in vivo electrophysiological recordings from unmyelinated afferents innervating the glabrous skin of the hind paw were performed in rats with an L5 spinal nerve lesion or sham surgery. Mechanical threshold and responsiveness to suprathreshold stimulation were tested before and after loperamide (1.25, 2.5 and 5 µg in 10 µl) or vehicle injection into the cutaneous receptive field. Loperamide dose-dependently decreased mechanosensitivity in unmyelinated afferents of nerve-injured and sham animals, and this effect was not blocked by naloxone pretreatment. We then investigated loperamide effects on nerve conduction by recording compound action potentials in vitro during incubation of the sciatic nerve with increasing loperamide concentrations. Loperamide dose-dependently decreased compound action potentials of myelinated and unmyelinated fibers (ED50 = 8 and 4 µg/10 µl, respectively). This blockade was not prevented by pre-incubation with naloxone. These results suggest that loperamide reversal of behavioral signs of neuropathic pain may be mediated, at least in part, by mechanisms independent of opioid receptors, most probably by local anesthetic actions.

Implantation of the Semicircular Canals With Preservation of Hearing and Rotational Sensitivity

It is possible to implant a stimulating electrode array in the semicircular canals without damaging rotational sensitivity or hearing. The electrodes will evoke robust and precisely controlled eye movements. A number of groups are attempting to develop a neural prosthesis to ameliorate abnormal vestibular function. Animal studies demonstrate that electrodes near the canal ampullae can produce electrically evoked eye movements. The target condition of these studies is typically bilateral vestibular hypofunction. Such a device could potentially be more widely useful clinically and would have a simpler roadmap to regulatory approval if it produced minimal or no damage to the native vestibular and auditory systems. An electrode array was designed for insertion into the bony semicircular canal adjacent to the membranous canal. It was designed to be sufficiently narrow so as to not compress the membranous canal. The arrays were manufactured by Cochlear, Ltd., and linked to a Nucleus Freedom receiver/stimulator. Seven behaviorally trained rhesus macaques had arrays placed in 2 semicircular canals using a transmastoid approach and "soft surgical" procedures borrowed from Hybrid cochlear implant surgery. Postoperative vestibulo-ocular reflex was measured in a rotary chair. Click-evoked auditory brainstem responses were also measured in the 7 animals using the contralateral ear as a control. All animals had minimal postoperative vestibular signs and were eating within hours of surgery. Of 6 animals tested, all had normal postoperative sinusoidal gain. Of 7 animals, 6 had symmetric postoperative velocity step responses toward and away from the implanted ear. The 1 animal with significantly asymmetric velocity step responses also had a significant sensorineural hearing loss. One control animal that underwent canal plugging had substantial loss of the velocity step response toward the canal-plugged ear. In 5 animals, intraoperative electrically evoked vestibular compound action potential recordings facilitated electrode placement. Postoperatively, electrically evoked eye movements were obtained from electrodes associated with an electrically evoked vestibular compound action potential wave form. Hearing was largely preserved in 6 animals and lost in 1 animal. It is possible to implant the vestibular system with prosthetic stimulating electrodes without loss of rotational sensitivity or hearing. Because electrically evoked eye movements can be reliably obtained with the assistance of intraoperative electrophysiology, it is appropriate to consider treatment of a variety of vestibular disorders using prosthetic electrical stimulation. Based on these findings, and others, a feasibility study for the treatment of human subjects with disabling Ménière's disease has begun.

Hydrophilic polymers enhance early functional outcomes after nerve autografting

BackgroundApproximately 12% of operations for traumatic neuropathy are for patients with segmental nerve loss, and less than 50% of these injuries obtain meaningful functional recovery. Polyethylene glycol (PEG) therapy has been shown to improve functional outcomes after nerve severance, and we hypothesized this therapy could also benefit nerve autografting. MethodsWe used a segmental rat sciatic nerve injury model in which we repaired a 0.5-cm defect with an autograft using microsurgery. We treated experimental animals with solutions containing methylene blue (MB) and PEG; control animals did not receive PEG. We recorded compound action potentials (CAPs) before nerve transection, after solution therapy, and at 72 h postoperatively. The animals underwent behavioral testing at 24 and 72 h postoperatively. After we euthanized the animals, we fixed the nerves, sectioned and immunostained them to allow for quantitative morphometric analysis. ResultsThe introduction of hydrophilic polymers greatly improved morphological and functional recovery of rat sciatic axons at 1–3 d after nerve autografting. Polyethylene glycol therapy restored CAPs in all animals, and CAPs were still present 72 h postoperatively. No CAPS were detectable in control animals. Foot Fault asymmetry scores and sciatic functional index scores were significantly improved for PEG therapy group at all time points (P < 0.05 and P < 0.001; P < 0.001 and P < 0.01). Sensory and motor axon counts were increased distally in nerves treated with PEG compared with control (P = 0.019 and P = 0.003). ConclusionsPolyethylene glycol therapy improves early physiologic function, behavioral outcomes, and distal axonal density after nerve autografting.

Electrocochleography during Cochlear Implantation for Hearing Preservation

To determine whether intraoperative electrocochleography during cochlear implant surgery provides online feedback to modify surgical procedure, reduce trauma, and increase preservation of residual hearing. Prospective cohort study. Tertiary referral center, Otolaryngology Department, University of Verona. Twenty-seven adult patients undergoing cochlear implant surgery who had low- to mid-frequency (0.25-2 kHz) auditory thresholds measured preoperatively were enrolled. Fifteen subjects had compound action potentials measured to assess cochlear function during surgery. In those patients, surgery was modified according to electrocochleographic feedback. Twelve control subjects underwent cochlear implant surgery with blinded electrocochleographic monitoring. The average preoperative pure-tone audiometry thresholds (0.25-2 kHz) were 74.3 ± 10.2 and 81.5 ± 12.7 dB hearing level (HL) in the electrocochleographic feedback and control cohorts, respectively (P > .05). Compound action potential recordings showed a mean maximum latency shift of 0.63 ± 0.36 ms and normalized amplitude deterioration of 59% ± 19% during surgery. All of these changes reverted to normal after electrode insertion in all but 1 subject in the electrocochleographic feedback group. The average shifts in postoperative pure-tone average threshold (0.25-2 kHz), evaluated before activation, were 8.7 ± 4.3 and 19.2 ± 11.4 dB HL in the electrocochleographic feedback and control cohorts, respectively (P = .0051). Complete hearing preservation (loss of ≤10 dB) at 1 month before activation was achieved in 85% (11/13) of electrocochleographic feedback subjects and in 33% (4/12) of control patients (P = .0154). Monitoring cochlear function with electrocochleography gives real-time feedback during surgery, providing objective data that might help in modifying the surgical technique in ways that can improve the rate of hearing preservation.

Diffusion Tensor Imaging Detected Optic Nerve Injury Correlates with Decreased Compound Action Potentials after Murine Retinal Ischemia

This study evaluated the function of mouse optic nerves after transient retinal ischemia using in vitro electrophysiologic recordings of compound action potentials (CAPs) correlated with diffusion tensor imaging (DTI) injury markers with confirmation by immunohistochemistry-determined pathology. Retinal ischemia was induced in 7- to 8-week-old female C57BL/6 mice by elevating intraocular pressure to 110 mm Hg for 60 minutes. At 3 and 7 days after retinal ischemia, optic nerves were removed for CAP measurements. The CAP amplitude was recorded using suction electrodes in isolated control and injured optic nerves followed by ex vivo DTI evaluation. After DTI, optic nerves were embedded in paraffin and cut for immunohistochemical analyses. Consistent with previous in vivo DTI measurements, a 25% decrease in axial diffusivity with normal radial diffusivity was seen at 3 days after retinal ischemia, suggesting axonal injury without myelin damage. At 7 days, there was no additional change in axial diffusivity compared with that at 3 days, but radial diffusivity significantly increased by 50%, suggestive of significant myelin damage due to sustained axonal injury. The relative anisotropy (RA) progressively decreased after retinal ischemia when compared with that of the controls. The CAP amplitude in injured nerves also progressively decreased after retinal ischemia, which correlated with the reduced RA (r = 0.80). This study suggests that CAP amplitude reflects both axonal and myelin integrity and RA is an optimal parameter for functional assessment compared with axial or radial diffusivity alone in murine optic nerves after retinal ischemia.

Electrocochleography in Round Window Vibrant Soundbridge Implantation

To determine the role of intraoperative electrocochleography to optimize the fitting of the floating mass transducer of the Vibrant Soundbridge on the round window membrane in patients with conductive and mixed hearing loss. Prospective cohort study. Tertiary referral center, Otolaryngology Department, University of Verona, Verona, Italy. Twenty-six adult patients suffering from chronic otitis media with moderate to severe conductive and mixed hearing loss, all with previous unsuccessful functional surgery, underwent round window vibroplasty. Thirteen subjects had intraoperative compound cochlear action potentials measured to assess vibroplasty coupling during and after surgery. In these patients, surgery was modified according to electrocochleographic feedback. The other 13 had vibroplasty without electrocochleography monitoring. The average preoperative air conduction and bone conduction thresholds (0.5-4 kHz) were not statistically significantly different between the 2 cohorts (P > .05). Compound action potential recordings indicated specific surgical modalities to optimize coupling of the floating mass transducer with the round window membrane. The average postoperative Vibrant Soundbridge-aided air conduction threshold improvements (0.5-4 kHz) were 54.6 ± 8.9 and 41.7 ± 11.1 dB HL, respectively, in the monitored and unmonitored cohorts (P = .0032). Improved round window vibroplasty outcomes are observed when the surgeon is promptly informed of the compound action potential changes induced by the floating mass transducer round window membrane vibroplasty and alters surgery accordingly. The key point for optimal coupling is a floating mass transducer in full contact with the round window membrane, free to vibrate without any contact with the surrounding bony structures and mobile footplate.

A novel method for recording neuronal depolarization with recording at 125–825 Hz: implications for imaging fast neural activity in the brain with electrical impedance tomography

Electrical impedance tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. Previous modelling suggested that applied current needed to be below 100Hz but the signal-to-noise ratio (SNR) recorded with scalp electrodes during evoked responses was too low to permit imaging. A novel method in which contemporaneous evoked potentials are subtracted is presented with current applied at 225Hz to cerebral cortex during evoked activity; although the signal is smaller than at DC by about 10×, the principal noise from the EEG is reduced by about 1000×, resulting in an improved SNR. It was validated with recording of compound action potentials in crab walking leg nerve where peak changes of -0.2% at 125 and 175Hz tallied with biophysical modelling. In recording from rat cerebral cortex during somatosensory evoked responses, peak impedance decreases of -0.07±0.006% (mean±SE) with a SNR of >50 could be recorded at 225Hz. This method provides a reproducible and artefact free means for recording resistance changes during neuronal activity which could form the basis for imaging fast neural activity in the brain.

Rat sciatic nerve repair with a poly‐lactic‐co‐glycolic acid scaffold and nerve growth factor releasing microspheres

The effect of microsphere delivered Nerve Growth Factor (NGF) in a poly-lactic-co-glycolic-acid (PLGA) 85/15 nerve conduit bridging a 10mm rat sciatic nerve gap was assessed, comparing nine groups (n = 6): PLGA conduits filled with saline, saline and NGF, saline with blank microspheres; four different NGF microspheres (5, 20, 50, and 100 mg/ml); an autologous graft and sciatic nerve gap. Histomorphometry, retrograde tracing, electrophysiology, and functional outcomes were evaluated up to 16 weeks. The autologous graft showed the largest fascicular area (0.65 mm(2) ) and had a significantly greater number of myelinated fibers (P < 0.0001). Electrophysiology showed Compound Muscle Action Potential (CMAP) recordings for the autologous graft returning at 6 weeks after nerve transection, reaching their highest amplitude of 3.6 mV at endpoint. No significant differences were found in functional evaluation between groups or between conduits with microspheres and the saline filled conduit. A PLGA 85/15 nerve conduit is capable of sustaining nerve regeneration. The microsphere delivery system does not interfere with regeneration.

A Model of Low-Level Primary Blast Brain Trauma Results in Cytoskeletal Proteolysis and Chronic Functional Impairment in the Absence of Lung Barotrauma

Shock-wave exposure from improvised explosive devices (IEDs) has been implicated as a possible contributing factor to neurological impairment reported in combat veterans. However, evidence-based substantiation of this implication, particularly for low-level exposure in the absence of external signs of trauma, remain elusive. Accordingly, we constructed an open-ended shock tube producing a short-duration, low-amplitude shockwave. Low-level (11.5 kPa static overpressure) complex shock-wave exposure in rats resulted in no histological evidence of lung injury. By contrast, delayed cytoskeletal proteolysis of αII-spectrin was detected in the cortex and hippocampus by 12 h post-injury. Cell death was minimal and localized predominantly in the corpus callosum and periventricular regions. These regions, with presumably different density interfaces, exhibit biological responses to shockwaves consistent with interface turbulence described by Richtmyer-Meshkov instability. Evoked compound action potential (CAP) recordings from the corpus callosum showed a significant increase in the duration of CAP responses at 14 and 30 days post-injury, and a gradual depression in the unmyelinated fiber amplitude. Shielding the head attenuated αII-spectrin cytoskeletal breakdown, thus directly implicating low-level shock-wave exposure as a cause of brain injury in the rat. Despite anatomical and scaling differences in rats compared to humans, the results suggest the potential for undiagnosed traumatic brain pathologies occurring in combat veterans following shock-wave exposure.

Effects of electrical stimulation on the acoustically evoked auditory-nerve response in guinea pigs with a high-frequency hearing loss

Criteria for cochlear implantation keep expanding and people with substantial residual low-frequency hearing are considered candidates for implantation nowadays. Therefore, electro-acoustical stimulation in the same ear (EAS) is receiving increasing interest. We have investigated the effects of intracochlear electrical stimulation on acoustically evoked auditory-nerve activity, using a forward masking paradigm. The stimulation electrode was placed in the basal turn of the cochlea. Compound action potential (CAP) recordings were performed in guinea pigs with severe high-frequency hearing loss and in normal-hearing control animals. In normal-hearing animals, electrical stimulation generally suppressed CAPs, especially at high acoustic frequencies (8 and 16 kHz) and low sound levels. At low frequencies (0.5 and 1 kHz), suppression was observed only at high sound levels. In animals with a high-frequency hearing loss, suppression of CAPs at low frequencies was substantially less compared to control animals, even at high current levels and temporal overlap of acoustic and electric stimuli. Hence, effects of electrical stimulation substantially differed between normal-hearing animals and animals with a high-frequency hearing loss. These findings stress the need for a proper animal model when investigating EAS. We conclude that in case of high-frequency loss, the basal part of the cochlea can be stimulated electrically with little effect on responses to low-frequency acoustic stimuli.

Spectral and polarization sensitivity of juvenile Atlantic salmon (Salmo salar): phylogenetic considerations

We were interested in comparing the characteristics of polarization sensitivity in Atlantic salmon to those in Pacific salmon. Here we show that the common ancestor to the clade containing Salmo salar, Oncorhynchus mykiss, O. nerka, O. clarkii and Salvelinus fontinalis has the trait of ultraviolet polarization sensitivity. We examined spectral and polarization sensitivity of juvenile Atlantic salmon (Salmo salar) using both optic nerve compound action potential (CAP) and electroretinogram (ERG) recordings. Our experiments employed photic manipulation to adjust the sensitivity of the four cone mechanisms of Atlantic salmon. A spectrally broad background was used to ensure a contribution of all cone mechanisms to both spectral and polarization sensitivity. Chromatic adaptation was used to isolate the sensitivity of each of the four cone mechanisms for both spectral and polarization sensitivity. Under spectrally broad conditions, UV sensitive (UVS), mid wavelength sensitive (MWS) and long wavelength sensitive (LWS) cone mechanisms contributed to polarization sensitivity. CAP recordings produced the typical 'W' shaped polarization sensitivity curve reflecting two active polarization detectors with peaks at e-vector orientations of 0 deg, 90 deg and 180 deg, and troughs at 30 deg and 150 deg. ERG recordings produced a four-peaked polarization sensitivity curve reflecting two active polarization detectors and negative feedback activity, with peaks at e-vectors 0 deg, 45 deg, 90 deg, 135 deg and 180 deg, and troughs at 30 deg, 60 deg, 120 deg and 150 deg. Polarization-sensitivity measurements of isolated cone mechanisms revealed two orthogonal polarization detector mechanisms in Atlantic salmon, identical to that found in rainbow trout and other Pacific salmonid fishes. Moreover, under spectrally broad background conditions, CAP and ERG polarization sensitivity of Atlantic salmon did not differ significantly from that reported in Pacific salmonids.

Exceptional high-frequency hearing and matched vocalizations in Australian pygopod geckos

We describe exceptional high-frequency hearing and vocalizations in a genus of pygopod lizards (Delma) that is endemic to Australia. Pygopods are a legless subfamily of geckos and share their highly specialized hearing organ. Hearing and vocalizations of amniote vertebrates were previously thought to differ clearly in their frequency ranges according to their systematic grouping. The upper frequency limit would thus be lowest in chelonians and increasingly higher in crocodilians, lizards, birds and mammals. We report data from four Delma species (D. desmosa, D. fraseri, D. haroldi, D. pax) from the Pilbara region of Western Australia that were studied using recordings of auditory-nerve compound action potentials (CAP) under remote field conditions. Hearing limits and vocalization energy of Delma species extended to frequencies far above those reported for any other lizard group, 14 kHz and >20 kHz, respectively. Their remarkable high-frequency hearing derives from the basilar papilla, and forward masking of CAP responses suggests a unique division of labor between groups of sensory cells within the hearing organ. These data also indicate that rather than having only strictly group-specific frequency ranges, amniote vertebrate hearing is strongly influenced by species-specific physical and ecological constraints.

Modular double sucrose gap apparatus for improved recording of compound action potentials from rat and mouse spinal cord white matter preparations

Compound action potential (CAP) recording is a powerful tool for studying the conduction properties and pharmacology of axons in multi-axonal preparations. The sucrose gap technique improves CAP recording by replacing the extracellular solution between the recording electrodes with a non-conductive sucrose solution to minimize extracellular shunting. The double sucrose gap (DSG), conferring similar advantages at the stimulation site, has been extensively used on guinea pig spinal cord white matter (WM) in vitro. Establishing the DSG methodology for WM preparations from smaller animals such as rats and mice is appealing due to their extensive use in basic and translationally oriented research. Here we describe a versatile modular DSG apparatus with rubber membrane separation of the compartments, suitable for WM strips from rat and mouse spinal cord. The small volumes of compartments (<0.1 ml) and the air-tight design allow perfusion rates of 0.5–1 ml/min with faster refreshment rates compared to commonly used 2–3 ml/min and larger compartments, providing economical usage of expensive pharmacological drugs. Our improved DSG design is particularly efficient for uncovering slower conducting, higher threshold CAP components, as demonstrated by recordings of C-wave (non-myelinated axons) in rat dorsal WM. In myelin-deficient Shiverer mice with genetically dysmyelinated axons, our DSG apparatus recordings revealed a multi-peak C-wave without preceding faster components. The improved stimulation and recording with our DSG apparatus, lowering the range of required stimulus intensities and reducing the artifact interference with recorded CAPs provide for critical technical advantages that allow for more detailed analysis of CAPs in relatively short preparations.

Site of cochlear stimulation and its effect on electrically evoked compound action potentials using the MED-EL standard electrode array

BackgroundThe standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720°. When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP) recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea.MethodsRecordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART™) feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation.ResultsFindings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions.ConclusionsObtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex.Trial registrationThe Clinical Investigation has the Competent Authority registration number DE/CA126/AP4/3332/18/05.

Glutamate receptor‐mediated ischemic injury of premyelinated central axons

Ischemic injury of axons is a feature of periventricular leukomalacia, a pathological correlate of cerebral palsy. Recent evidence suggests that axons are damaged before they receive the first layer of compact myelin. Here we examine the cellular mechanisms underlying ischemic-type injury of premyelinated central axons. Two-thirds of axons in the postnatal day 10 (P10) rat optic nerve are small premyelinated axons (<0.4microm in diameter), and one-third have undergone radial expansion in preparation for glial contact and the onset of myelination. Compound action potential recording and quantitative electron microscopy were used to examine the effect of modeled ischemia (oxygen-glucose deprivation) upon these two axon populations. Glutamate receptor (GluR) expression was investigated using polymerase chain reaction (PCR) and immunostaining approaches at the confocal light and ultrastructural levels. Oxygen-glucose deprivation produced action potential failure and focal breakdown of the axolemma of small premyelinated axons at sites of contact with oligodendrocyte processes, which were also disrupted. The resulting axon loss was Ca(2+)-dependent, Na(+)- and Cl(-)-independent, and required activation of N-methyl-D-aspartic acid (NMDA) and non-NMDA GluRs. NMDA receptor expression was localized to oligodendrocyte processes at sites of contact with premyelinated axons, in addition to expression within compact myelin. No periaxonal NMDA receptor expression was observed on oligodendrocyte processes ensheathing large premyelinated axons and no protective effect of GluR block was observed in these axons. NMDA receptor-mediated injury to oligodendrocyte processes navigating along small premyelinated axons precedes damage to the underlying axon, a phenomena that is lost following radial expansion and subsequent oligodendrocyte ensheathment.

Reducing blanking artifact in electrically evoked compound action potentials

The main source of distortion in the recording of the electrically evoked compound action potentials is the stimulus artifact. The popular hardware blanking technique tends to reduce this artifact, but generates a blanking artifact as a consequence of the transient state in the amplifier. In this paper we propose two techniques to deal with the blanking artifact. The proposed techniques are combined with conventional and generalized alternating stimulation in order to reduce both stimulus and blanking artifacts in the recording of the evoked potentials. A comparison over 126 evoked potential recordings reveals that the proposed blanking artifact reduction methods improve the quality of electrically evoked compound action potential recordings.