外周诱发电位的模型研究

本文根据容积导体中有关动作电位的电生理理论,用三点源模型模拟单根纤维动作电位(SFAP),并假设神经束的复合动作电位(CAP)是由SFAP线性叠加而成,给出了神经束CAP的模型.通过运用上述模型,计算了正常人正中神经纤维传导速度分布,分析了刺激腕部正中神经引导的传感诱发电位(SEP)的N~-_9成分;另外,还得出一些描述此外周传导通路性质的其它参数,如平均传导速度、神经纤维活动最可几传速度分布范围等.此方法可用来研究其它各种外围诱发电位.     

Pulsed magnetic fields enhance the rate of recovery of damaged nerve excitability

Pulsed magnetic fields (PMFs) have well‐known beneficial effects on nerve regeneration. However, little research has examined the nerve conduction characteristics of regenerating peripheral nerves under PMF. The main goal of this study was to examine the conduction characteristics of regenerating peripheral nerves under PMFs. The sucrose‐gap recording technique was used to examine the conduction properties of injured sciatic nerves of rats exposed to PMF. Following the injury, peripheral nerves were very sensitive to repetitive stimulation. When the stimulation frequency was increased, the amplitude of the compound action potential (CAP) decreased more at 15 days post‐crush injury (dpc) than at 38 dpc. PMF treatment for 38 days after injury caused significant differences in the conduction of CAPs. Moreover, application of PMF ameliorated the abnormal electrophysiological activities of nerves such as hyperpolarizing afterpotentials and delayed depolarizations that were revealed by 4‐aminopyridine (4‐AP). Consequently, characteristic findings in impulse conduction of recovered nerves under PMF indicate that the observed abnormalities in signaling or aberrant ion channel functions following injury may be restored by PMF application. Bioelectromagnetics 32:200–208, 2011. © 2010 Wiley‐Liss, Inc.     

Search for frequency-specific effects of millimeter-wave radiation on isolated nerve function

Effects of a short-term exposure to millimeter waves (CW, 40–52 GHz, 0.24–3.0 mW/cm²) on the compound action potential (CAP) conduction were studied in an isolated frog sciatic nerve preparation. CAPs were evoked by either a low-rate or a high-rate electrical stimulation of the nerve (4 and 20 paired pulses/s, respectively). The low-rate stimulation did not alter the functional state of the nerve, and the amplitude, latency, and peak latency of CAPs could stay virtually stable for hours. Microwave irradiation for 10–60 min at 0.24–1.5 mW/cm², either at various constant frequencies or with a stepwise frequency change (0.1 or 0.01 GHz/min), did not cause any detectable changes in CAP conduction or nerve refractoriness. The effect observed under irradiation at a higher field intensity of 2–3 mW/cm² was a subtle and transient reduction of CAP latency and peak latency along with a rise of the test CAP amplitude. These changes could be evoked by any tested frequency of the radiation; they reversed shortly after cessation of exposure and were both qualitatively and quantitatively similar to the effect of conventional heating of 0.3–0.4°C. The high-rate electrical stimulation caused gradual and reversible decrease of the amplitude of conditioning and test CAPs and increased their latencies and peak latencies. These changes were essentially the same with and without irradiation (2.0–2.7 or 0.24–0.28 mW/cm²), except for attenuation of the decrease of the test CAP amplitude. This effect was observed at both field intensities, but was statistically significant only for certain frequencies of the radiation. Within the studied limits, this effect appeared to be dependent on the frequency rather than on the intensity of the radiation, but this observation requires additional experimental confirmation. Bioelectromagnetics 18:324–334, 1997. © 1997 Wiley-Liss, Inc.     

Presynaptic augmentation induced by NaF in sympathetic ganglion of bullfrog

Effects of NaF on the synaptic transmission of bullfrog sympathetic ganglia were studied by extra- and intracellular recordings. The results obtained were as follows: 1) The amplitude of the orthodromic compound action potential (CAP) evoked by preganglionic nerve stimulation was remarkably augmented with 10 microM NaF, whereas that of the antidromic CAPs remained unchanged with the same dose of NaF. The low amplitude of the orthodromic CAP which was diminished by a low-Ca2(+)-ringer's solution reversed with an additional administration of NaF. The amplitudes of the orthodromic CAPs were enhanced by phosphodiesterase inhibitors such as isobutylmethylxanthine, theophylline, and physostigmine. In addition, augmentation of the orthodromic CAPs was induced by an adenylate cyclase activator (forskolin) and d.b-cAMP; however, its augmented responses were not affected by an additional administration of NaF. 2) In the intracellular recording, NaF showed no effect on the resting membrane potential and depolarizing response induced by acetylcholine. However, the EPSP appearing in the phase of afterhyperpolarization of the orthodromic action potential was significantly increased by NaF, whereas no effect was found on the antidromic action potential. In order to evaluate these findings, effects of NaF on the decreased low-Ca2(+)-action potential were observed. After application of NaF, the low-Ca2(+)-orthodromic EPSPs were reversed, and when the height of the EPSP was raised to the critical firing level, a spike potential was driven in the cell. These facts suggest that the site of NaF action seems to exist in the presynaptic rather than postsynaptic process. Furthermore, it suggests that NaF probably acts on Gs-protein which activates adenylate cyclase at the presynaptic membrane. This resulted in a great increase in intracellular cAMP at the synaptic terminal and it triggered the Ca2(+)-increase. As an inevitable consequence, release of transmitter from the nerve terminals of the frog sympathetic ganglion was finally facilitated. These factors supposedly resulted in augmentation of the amplitude of the orthodromic CAP.     

Bisphenol A inhibits compound action potentials in the frog sciatic nerve in a manner independent of estrogen receptors

Although the endocrine disruptor bisphenol A (BPA) is reported to inhibit nerve conduction, the underlying mechanisms are unclear. Therefore, in the present study, we examined the effect of BPA on compound action potentials (CAPs) recorded from the frog sciatic nerve using the air-gap method. Treatment of the sciatic nerve with BPA (0.5 mM) for 20 min reduced the peak amplitude of the CAP by approximately 60% in a partially reversible manner. The reduction in the CAP peak amplitude was concentration-dependent, with a half-maximal inhibitory concentration (IC₅₀) value of 0.31 mM. This effect of BPA was unaffected by an estrogen-receptor antagonist, 4-hydroxytamoxifen, which by itself reduced CAP peak amplitude, with an IC₅₀ value of 0.26 mM (comparable to that of BPA). The natural estrogen 17β-estradiol, at the highest dissolvable concentration (0.05 mM), had an effect similar to that of BPA. The IC₅₀ value of BPA was comparable to those of some local anesthetics in inhibiting frog CAPs. Our findings suggest that BPA inhibits nerve conduction in a manner independent of estrogen receptors. This action of BPA may underlie, at least in part, the neurotoxicity of the compound.     

Inhibitory effects of opioids on compound action potentials in frog sciatic nerves and their chemical structures

An opioid tramadol more effectively inhibits compound action potentials (CAPs) than its metabolite mono-O-demethyl-tramadol (M1). To address further this issue, we examined the effects of opioids (morphine, codeine, ethylmorphine and dihydrocodeine) and cocaine on CAPs by applying the air-gap method to the frog sciatic nerve. All of the opioids at concentrations less than 10 mM reduced the peak amplitude of the CAP in a reversible and dose-dependent manner. The sequence of the CAP peak amplitude reductions was ethylmorphine>codeine>dihydrocodeine> or = morphine; the effective concentration for half-maximal inhibition (IC(50)) of ethylmorphine was 4.6 mM. All of the CAP inhibitions by opioids were resistant to a non-specific opioid-receptor antagonist naloxone. The CAP peak amplitude reductions produced by morphine, codeine and ethylmorphine were related to their chemical structures in such that this extent enhanced with an increase in the number of -CH(2) in a benzene ring, as seen in the inhibitory actions of tramadol and M1. Cocaine reduced CAP peak amplitudes with an IC(50) value of 0.80 mM. It is concluded that opioids reduce CAP peak amplitudes in a manner being independent of opioid-receptor activation and with an efficacy being much less than that of cocaine. It is suggested that the substituted groups of -OH bound to the benzene ring of morphine, codeine and ethylmorphine as well as of tramadol and M1, the structures of which are quite different from those of the opioids, may play an important role in producing nerve conduction block.     

A Novel Approach for Studying the Physiology and Pathophysiology of Myelinated and Non-Myelinated Axons in the CNS White Matter

Advances in brain connectomics set the need for detailed knowledge of functional properties of myelinated and non-myelinated (if present) axons in specific white matter pathways. The corpus callosum (CC), a major white matter structure interconnecting brain hemispheres, is extensively used for studying CNS axonal function. Unlike another widely used CNS white matter preparation, the optic nerve where all axons are myelinated, the CC contains also a large population of non-myelinated axons, making it particularly useful for studying both types of axons. Electrophysiological studies of optic nerve use suction electrodes on nerve ends to stimulate and record compound action potentials (CAPs) that adequately represent its axonal population, whereas CC studies use microelectrodes (MEs), recording from a limited area within the CC. Here we introduce a novel robust isolated "whole" CC preparation comparable to optic nerve. Unlike ME recordings where the CC CAP peaks representing myelinated and non-myelinated axons vary broadly in size, "whole" CC CAPs show stable reproducible ratios of these two main peaks, and also reveal a third peak, suggesting a distinct group of smaller caliber non-myelinated axons. We provide detailed characterization of "whole" CC CAPs and conduction velocities of myelinated and non-myelinated axons along the rostro-caudal axis of CC body and show advantages of this preparation for comparing axonal function in wild type and dysmyelinated shiverer mice, studying the effects of temperature dependence, bath-applied drugs and ischemia modeled by oxygen-glucose deprivation. Due to the isolation from gray matter, our approach allows for studying CC axonal function without possible "contamination" by reverberating signals from gray matter. Our analysis of "whole" CC CAPs revealed higher complexity of myelinated and non-myelinated axonal populations, not noticed earlier. This preparation may have a broad range of applications as a robust model for studying myelinated and non-myelinated axons of the CNS in various experimental models.     

Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves

AimsAlthough capsaicin not only activates transient receptor potential vanilloid-1 (TRPV1) channels but also inhibits nerve conduction, the latter action has not yet been fully examined. The purpose of the present study was to know whether various vanilloids have an inhibitory action similar to that of capsaicin and further to compare their actions with that of local anesthetic procaine.Main methodsFast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method.Key findingsCapsaicin reversibly and concentration-dependently reduced the peak amplitude of the CAP. TRPV1 antagonist capsazepine did not affect the capsaicin activity, and powerful TRPV1 agonist resiniferatoxin had no effect on CAPs, indicating no involvement of TRPV1 channels. Capsaicin analogs and other various vanilloids also inhibited CAPs in a concentration-dependent manner. An efficacy sequence of these inhibitions was capsaicin = dihydrocapsaicin > capsiate > eugenol > guaiacol ≥ zingerone ≥ vanillin > vanillylamine. Vanillic acid had almost no effect on CAPs; olvanil and curcumin appeared to be effective less than capsaicin. Capsaicin and eugenol were, respectively, ten- and two-fold effective more than procaine in CAP inhibition, while each of guaiacol, zingerone and vanillin was five-fold effective less than procaine.SignificanceVarious vanilloids exhibit CAP inhibition, the extent of which is determined by the property of the side chain bound to the vanillyl group, and some of them are more effective than procaine. These results may serve to unveil molecular mechanisms for capsaicin-induced conduction block and to develop antinociceptive drugs related to capsaicin.     

Ca2+ -free medium enhances the magnitude of slow peak in compound action potential of frog sciatic nerve in vitro

The present investigation was carried out to know the effect of Ca2+ on different peaks of compound action potential (CAP) representing the fibers having different conduction velocity. CAP was recorded from a thin bundle of nerve fibers obtained from desheathed frog sciatic nerve. Suction electrodes were used for stimulating and recording purposes. In Ca2+ -free amphibian Ringer, two distinct peaks (Peak-I and Peak-II) were observed. The threshold, conduction velocity (CV), amplitude and duration of Peak-I were 0.32 +/- 0.02 V, 56 +/- 3.0 m/sec, 2.1 +/- 0.2 mV and 0.75 +/- 0.1 ms, respectively. The Peak-II exhibited ten times greater threshold, eight times slower CV, three times lower amplitude and four times greater duration as compared to Peak-I. Addition of 2 mM Ca2+ in the bathing medium did not alter CAP parameters of Peak-I excepting 25% reduction in CV. But, in Peak-II there was 70-75% reduction in area and amplitude. The concentration-attenuation relation of Peak-II to various concentrations of Ca2+ was nonlinear and 50% depression occurred at 0.35 mM of Ca2+. Washing with Ca2+ -free solution with or without Mg2+ (2 mM)/verapamil (10 microM) could not reverse the Ca2+ -induced changes in Peak-II. Washing with Ca2+ -free solution containing EDTA restored 70% of the response. The results indicate that Ca2+ differentially influence fast and slow conducting fibers as the activity of slow conducting fibers is greatly suppressed by external calcium.     

Circadian pacemaker neurons: membranes and molecules

1. A circadian pacemaker is located in the eyes of a variety of marine gastropods, including Aplysia and Bulla. It produces a circadian rhythm in the frequency of spontaneously occurring optic nerve (ON) compound action potentials (CAPs). The circadian pacemaker in Bulla includes a population of 100 retinal pacemaker neurons, that produce the rhythmic CAP output. Intracellular recording from the Bulla pacemaker neurons has yielded new insight into their time-keeping ability. 2. Intracellular injection of Lucifer yellow dye into a single pacemaker neuron results in the spread of dye to several neurons. This dye coupling is presumably mediated by the gap junctions among neurons that are responsible for the synchronous firing of the population of pacemaker neurons and the generation of ON CAPs. 3. The circadian pacemaker in each eye interacts with the paired pacemaker in the contralateral eye. The interaction results in the coordinating firing of CAPs from each eye and in the coordinated phasing of the circadian rhythms of CAP activity generated in each eye. This interaction occurs by reciprocal excitatory chemical synapses. These synaptic receptors occur in the ON as well as in the retinal neuropil and CAP synchrony occurs in the ON as well as in the basal retina. 4. Pacemaker neurons are depolarized by 5-HT and membrane permeable cAMP analogues. The membrane resistance increases during the depolarization suggesting a background potassium current is decreased. 5. The tetrapeptide FMRF-HN2 hyperpolarizes the pacemaker neurons. It reverses the effect of 5-HT and cAMP, suggesting 5-HT and FMRF-NH2 may be acting on the same membrane channel, the S channel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of the relationship between the rise-time and the amplitude of single-fibre potentials in human muscles

Using the core-conductor theory, a single fibre action potential (SFAP) can be expressed as the convolution of a biolectrical source and a weight function. In the Dimitrov–Dimitrova (D–D) SFAP convolutional model, the first temporal derivative of the intracellular action potential (IAP) is used as the source. The present work evaluates the relationship between the SFAP peak-to-peak amplitude (V_pp) and peak-to-peak interval (rise-time, RT) at different fibre-to-electrode distances using simulated signals obtained by the D–D model as well as real recordings. With a single fibre electrode, we recorded 63 sets of consecutive SFAPs from the m. tibialis anterior of four normal subjects. The needle was intentionally moved whilst recording each SFAP set. We used the observed changes in RT and V_pp within each SFAP set as a point of reference with which to evaluate how closely the relationship between RT and V_pp provided by the D–D model reflects real data. We found that half of the recorded SFAP sets had rise-times higher than those generated by the D–D model. We also showed the influence of the IAP spatial length on the sensitivity of RT and V_pp with radial distance. The study reveals some inaccuracies in simulated SFAPs whose origin might be related to the assumptions made in the core-conductor theory.     

Effects of essential oil of Alpinia zerumbet on the compound action potential of the rat sciatic nerve.

Alpinia zerumbet, known popularly as "col?nia" in Northeastern Brazil, is a medicinal plant that has been used widely in folk medicine as teas and infusions for the treatment of intestinal and cardiovascular diseases, including arterial hypertension. Our previous studies have demonstrated that the essential oil of A. zerumbet (OEAZ) is very active on excitable tissues, such as smooth muscle, and in this study we verified its effects on the compound action potential (CAP) of rat sciatic nerve. EOAZ induced a dose-dependent blockade of the CAP. Control peak-to-peak amplitude and conduction velocity of CAPs were 7.6 +/- 0.43 mV and 80.6 +/- 3.19 m/s, respectively. At 60 microg/ml, EOAZ induced no demonstrable effect. Conduction velocity was significantly reduced at 180 min of preparation exposure to 100 microg/ml of EOAZ. At 300, 600 and 2000 microg/ml doses of EOAZ, the peak-to-peak amplitudes of CAPs following 180 min exposure of the nerve to the drug were reduced significantly, to 75.3 +/- 7.36%, 50.45 +/- 2.17% and 0% respectively, of control value. Conduction velocity was reduced significantly by 300, 600 and 2000 microg/ml of EOAZ, at 180 min, to 83.61 +/- 3.28%, 64.06 +/- 8.21% and 22.7 +/- 5.79%, respectively, of control value. All these effects developed slowly and were reversible upon a 180-min wash.     

Insect visceral muscle. Excitation and conduction in the proctodeal muscles

Bioelectrical potentials were studied from longitudinal muscle fibres of the cockroach proctodeum. The muscle bundle receives a polyaxonal innervation from both anterior and posterior branches of the anterior proctodeal nerve. Evoked post-synaptic potentials consisted of two independent, but similar components generated through the two branches. An action potential in the muscle fibre could be generated with single branch stimulation, and more readily by co-operation of excitation in the two nerve branches.Any part of the muscle was capable of acting as a pacemaker for myogenic rhythmic action potential, and the pacemaker region fluctuated with time. Excitation of the muscle could spread in two ways, directly myogenic and indirectly through nerve tracts. Myogenic conduction (2 cm/sec) was observed to be slower than neural conduction (35–38 cm/sec) in the muscle bundle.     

Effects of AF64A on cholinergic neurotransmission in the sixth abdominal ganglion of the cockroach

1. The effects of ethylcholine mustard aziridinium ion (AF64A) on the cholinergic neurotransmission in the sixth abdominal ganglion of the cockroach were studied electrophysiologically and morphologically. 2. The pre- and post-synaptic compound action potentials (CAPs) elicited via electrical stimulation of the presynaptic fibers were recorded extracellularly. 3. The amplitude of both CAPs was depressed by AF64A (50-400 microM) in a concentration- and time-dependent manner. 4. At a high concentration, they were abolished but 100 microM of carbachol still evoked the postsynaptic event. 5. Electron microscopic observation of AF64A-treated ganglia showed that nerve terminals containing small lucent vesicles could not be observed but those containing dense core or large granular vesicles changed only slightly in shape. 6. These results suggest that AF64A is selectively neurotoxic for the presynaptic cholinergic neurons in the sixth abdominal ganglion of the cockroach.     

Structure of the N-terminal domain of the adenylyl cyclase-associated protein (CAP) from Dictyostelium discoideum

Cyclase-associated proteins (CAPs) are widely distributed and highly conserved proteins that regulate actin remodeling in response to cellular signals. The N termini of CAPs play a role in Ras signaling and bind adenylyl cyclase; the C termini bind to G-actin and thereby alter the dynamic rearrangements of the microfilament system. We report here the X-ray structure of the core of the N-terminal domain of the CAP from Dictyostelium discoideum, which comprises residues 51-226, determined by a combination of single isomorphous replacement with anomalous scattering (SIRAS). The overall structure of this fragment is an alpha helix bundle composed of six antiparallel helices. Results from gel filtration and crosslinking experiments for CAP(1-226), CAP(255-464), and the full-length protein, together with the CAP N-terminal domain structure and the recently determined CAP C-terminal domain structure, provide evidence that the functional structure of CAP is multimeric.     

NMR structural characterization of the N-terminal domain of the adenylyl cyclase-associated protein (CAP) from Dictyostelium discoideum

Cyclase-associated proteins (CAPs) are highly conserved, ubiquitous actin binding proteins that are involved in microfilament reorganization. The N-termini of CAPs play a role in Ras signaling and bind adenylyl cyclase; the C-termini bind to G-actin. We report here the NMR characterization of the amino-terminal domain of CAP from Dictyostelium discoideum (CAP(1-226)). NMR data, including the steady state (1)H-(15)N heteronuclear NOE experiments, indicate that the first 50 N-terminal residues are unstructured and that this highly flexible serine-rich fragment is followed by a stable, folded core starting at Ser 51. The NMR structure of the folded core is an alpha-helix bundle composed of six antiparallel helices, in a stark contrast to the recently determined CAP C-terminal domain structure, which is solely built by beta-strands.     

Inhibition by menthol and its related chemicals of compound action potentials in frog sciatic nerves

AimsTransient receptor potential (TRP) vanilloid-1 (TRPV1) and melastatin-8 (TRPM8) channels play a role in transmitting sensory information in primary-afferent neurons. TRPV1 agonists at high concentrations inhibit action potential conduction in the neurons and thus have a local anesthetic effect. The purpose of the present study was to know whether TRPM8 agonist menthol at high concentrations has a similar action and if so whether there is a structure–activity relationship among menthol-related chemicals.Main methodsCompound action potentials (CAPs) were recorded from the frog sciatic nerve by using the air-gap method.Key findings(?)-Menthol and (+)-menthol concentration-dependently reduced CAP peak amplitude with the IC₅₀ values of 1.1 and 0.93 mM, respectively. This (?)-menthol activity was resistant to non-selective TRP antagonist ruthenium red; TRPM8 agonist icilin did not affect CAPs, indicating no involvements of TRPM8 channels. p-Menthane, (+)-limonene and menthyl chloride at 7–10 mM minimally affected CAPs. On the other hand, (?)-menthone, (+)-menthone, (?)-carvone, (+)-carvone and (?)-carveol (in each of which chemicals OH or O group was added to p-menthane and limonene) and (+)-pulegone inhibited CAPs with extents similar to that of menthol. 1,8-Cineole and 1,4-cineole were less effective while thymol and carvacrol were more effective than menthol in inhibiting CAPs.SignificanceMenthol-related chemicals inhibited CAPs and were thus suggested to exhibit local anesthetic effects comparable to those of lidocaine and cocaine as reported previously for frog CAPs. This result may provide information to develop local anesthetics on the basis of the chemical structure of menthol.     

Stretch-induced nerve conduction deficits in guinea pig ex vivo nerve

In the current communication, we characterized supraphysiologic elongations that elicited short-term nerve dysfunction. This was accomplished by assessing the electrophysiology of guinea pig tibial and peroneal nerves at predetermined elongation magnitudes. Results showed that a longitudinal supraphysiological stretch of lambda = 1.05 caused a 16% reduction in the mean compound action potential (CAP) amplitude. Upon relaxation to physiologic length, a full recovery in the CAP was observed. At lambda = 1.10, the CAP decreased by 50% with an 88% recovery after relaxation. For a supraphysiologic stretch of lambda = 1.20, severe conduction block with minimal acute recovery was observed. Latency also increased during periods of stretch and was proportional to the stretch magnitude. Additional studies showed some electrophysiological recovery during the sustained stretch phase. This attribute may be related to internal stress relaxation mechanisms. Since whole nerve elongations are averaged global deformations, we also used an incremental digital image correlation (DIC) technique to characterize the strain at the micro-tissue level. The DIC analysis revealed considerable heterogeneity in the planar strain field, with some regions exhibiting strains above the macroscale stretch. This non-uniformity in the strain map arises from structural inconsistencies of the nerve and we presume that zones of high local strain may translate into the observed conduction deficits.     

Frequency Distribution of F-Latencies (DFL) has Physiological Significance and Gives Distribution of Conduction Velocity (DCV) of Motor Nerve Fibres With Implications for Diagnosis

On electrical stimulation of a peripheral motor nerve, a delayed and reduced F-response is obtained, which is known to occur due to random backfiring of a few percent of the motor nerve fibres at the spinal end after antidromic conduction. F-latencies obtained from multiple stimulations vary in latency, size and shape because of this randomness. We hypothesised that, being a random process, recruitment of fibres for F-response would depend on the distribution of conduction velocity (DCV) for motor nerve fibres directly, and therefore, a frequency distribution of F-latencies (DFL) from such multiple F-responses would be an approximate mirror image of DCV, latency being inversely proportional to velocity. First, obtaining DFL from many human subjects, we have shown that this is a reproducible parameter for a nerve trunk of a subject, and hence reveals a new physiological phenomenon. DFL has a single peaked distribution, which is also expected for the DCV of a normal healthy motor nerve. To validate its hypothesised relationship to DCV further, DFLs were obtained from both median nerves of patients with unilateral carpal tunnel syndrome (CTS). The patterns of DFL from both sides remained almost the same except for a delay shift equal to that in between the two M-responses, which lends support to this hypothesis. DFL, and DCV as its suggested mirror image, appear to change systematically with certain known disorders such as cervical spondylosis, even at a subclinical stage, which needs further study. This also indicates that DFL may become a new and improved investigative diagnostic tool in neurophysiology.     

Contrasting mechanisms for hidden hearing loss: Synaptopathy vs myelin defects

Hidden hearing loss (HHL) is an auditory neuropathy characterized by normal hearing thresholds but reduced amplitudes of the sound-evoked auditory nerve compound action potential (CAP). In animal models, HHL can be caused by moderate noise exposure or aging, which induces loss of inner hair cell (IHC) synapses. In contrast, recent evidence has shown that transient loss of cochlear Schwann cells also causes permanent auditory deficits in mice with similarities to HHL. Histological analysis of the cochlea after auditory nerve remyelination showed a permanent disruption of the myelination patterns at the heminode of type I spiral ganglion neuron (SGN) peripheral terminals, suggesting that this defect could be contributing to HHL. To shed light on the mechanisms of different HHL scenarios observed in animals and to test their impact on type I SGN activity, we constructed a reduced biophysical model for a population of SGN peripheral axons whose activity is driven by a well-accepted model of cochlear sound processing. We found that the amplitudes of simulated sound-evoked SGN CAPs are lower and have greater latencies when heminodes are disorganized, i.e. they occur at different distances from the hair cell rather than at the same distance as in the normal cochlea. These results confirm that disruption of heminode positions causes desynchronization of SGN spikes leading to a loss of temporal resolution and reduction of the sound-evoked SGN CAP. Another mechanism resulting in HHL is loss of IHC synapses, i.e., synaptopathy. For comparison, we simulated synaptopathy by removing high threshold IHC-SGN synapses and found that the amplitude of simulated sound-evoked SGN CAPs decreases while latencies remain unchanged, as has been observed in noise exposed animals. Thus, model results illuminate diverse disruptions caused by synaptopathy and demyelination on neural activity in auditory processing that contribute to HHL as observed in animal models and that can contribute to perceptual deficits induced by nerve damage in humans.