Manifestations of dynamic coding of the amplitude-modulated sounds on the level of auditory nerve fibres

Average firing rate of the auditory nerve fiber as function of the level of the tone with the frequency equal to characteristic frequency of the fibers, can be defined as an input-output characteristic. It is known that the steepening of the input-output characteristic of the real auditory nerve fiber is more, and the width is less than the spontaneous activity of the fiber. The latter characterizes fiber's ability to generate spikes, if the stimulus is absent. However it is known, that the real auditory nerve fibers with low spontaneous activity reproduce amplitude modulation of the signals much better, than the fibers with high spontaneous activity. From the results of simulation experiments, it follows that the dynamic properties of the auditory nerve fibers, providing fine tuning or adaptation of a fiber threshold under the stimulus level but not the static input-output characteristics, are the reason of fibers reproduction of stimuli amplitude modulations. However the auditory nerve fibers with high spontaneous activity due to abrupt input-output characteristic are capable to reproduce modulations of sounds whose levels are lower than a threshold of the fiber, if a weak signal adds to a weak broadband noise. This is a phenomenon of stochastic resonance found in the reactions of auditory nerve fibers.     

Functional correlates of characteristic frequency in single cochlear nerve fibers of the Mongolian gerbil

Summary Single-unit recordings obtained from the auditory nerve of the Mongolian gerbil, Meriones unguiculatus, revealed functional differences in the response properties of neurons tuned to low and high frequencies. The distribution of neural thresholds displayed a distinct rise for auditory nerve fibers with characteristic frequencies] (CFs) between 3–5 kHz. This frequency band also marked abrupt changes in both the distribution of spontaneous discharge rates and the shape of the neural tuning curve. For neurons of all CFs, spontaneous firing rates were inversely related to neural threshold but unrelated to sharpness of neural tuning. The range of CF thresholds encountered, even when data from many animals were combined, rarely exceeded 20 dB, suggesting that cochlear nerve responses obtained from this species display little inter-animal variability. These results are compared with similar data from other species and discussed in terms of recent studies on sound communication and cochlear anatomy in gerbils.Abbreviations CF characteristic frequency - SR spontaneous discharge rate     

Some properties of auditory neuron’s model trained by firing caused by tones modulated by low-frequency noise

In many sensory systems the formation of burst firing can be observed along a way from the periphery to the central nuclei. We investigate the putative transformation of spontaneous activity in the auditory pathway using a neuron model trained by real firing recorded in the auditory nuclei of the frog. The model has 200 separate inputs (neuronal spines). It is supposed that every spine is a coincidence detector. Its output (synaptic potential) sharply increases at emergence of the precisely certain interpulse interval in an input pulse sequence. If the total synaptic potentials excess a threshold, the model generates output spike, which changes weight of all spines according to the simplified Hebb principle. The model was trained by real firing caused in the auditory nuclei of the frog by tones modulated by low-frequency noise in the frequency ranges of 0–15 Hz, 0–50 Hz or 0–150 Hz. After that training the synaptic weights of every spine essentially changed. Thus, along with some increase of weights of spines tuned to boundary frequencies of modulating noise, the most characteristic change was the emphasizing weights of spines tuned to short interpulse intervals. As a result the spontaneous activity passed through the trained model became much more bursting. Efficiency of a signal transmission in model was higher when input spontaneous activity of real cells contains bursts of spikes. Results of modeling are discussed in connection with modern physiological data demonstrating the functional advantage of bursting.     

关于听神经放电时间构型听觉模型的研究

提出了一个基于听神经放电时间模式的高度简化的听觉模型。该模型由两部分组成。第一部分是一个耳蜗模型,其中HRB和LRB粗略的模拟不同自发放电率听神经纤维的某些放电特性。第二部分是一个转换器,它产生一个频域表示：选择性同步滤波器数（Numbers of Selectively Synchronized Filters,NSSF)。这种NSSF频谱表示具有清,能强调高频域的频率分量及强调频谱的变化对比等几个特点。     

A dynamical point process model of auditory nerve spiking in response to complex sounds

In this paper, we develop a dynamical point process model for how complex sounds are represented by neural spiking in auditory nerve fibers. Although many models have been proposed, our point process model is the first to capture elements of spontaneous rate, refractory effects, frequency selectivity, phase locking at low frequencies, and short-term adaptation, all within a compact parametric approach. Using a generalized linear model for the point process conditional intensity, driven by extrinsic covariates, previous spiking, and an input-dependent charging/discharging capacitor model, our approach robustly captures the aforementioned features on datasets taken at the auditory nerve of chinchilla in response to speech inputs. We confirm the goodness of fit of our approach using the Time-Rescaling Theorem for point processes.     

Constructing Noise-Invariant Representations of Sound in the Auditory Pathway

Identifying behaviorally relevant sounds in the presence of background noise is one of the most important and poorly understood challenges faced by the auditory system. An elegant solution to this problem would be for the auditory system to represent sounds in a noise-invariant fashion. Since a major effect of background noise is to alter the statistics of the sounds reaching the ear, noise-invariant representations could be promoted by neurons adapting to stimulus statistics. Here we investigated the extent of neuronal adaptation to the mean and contrast of auditory stimulation as one ascends the auditory pathway. We measured these forms of adaptation by presenting complex synthetic and natural sounds, recording neuronal responses in the inferior colliculus and primary fields of the auditory cortex of anaesthetized ferrets, and comparing these responses with a sophisticated model of the auditory nerve. We find that the strength of both forms of adaptation increases as one ascends the auditory pathway. To investigate whether this adaptation to stimulus statistics contributes to the construction of noise-invariant sound representations, we also presented complex, natural sounds embedded in stationary noise, and used a decoding approach to assess the noise tolerance of the neuronal population code. We find that the code for complex sounds in the periphery is affected more by the addition of noise than the cortical code. We also find that noise tolerance is correlated with adaptation to stimulus statistics, so that populations that show the strongest adaptation to stimulus statistics are also the most noise-tolerant. This suggests that the increase in adaptation to sound statistics from auditory nerve to midbrain to cortex is an important stage in the construction of noise-invariant sound representations in the higher auditory brain.     

Analog modelling of cochlear adaptation

Adaptation phenomena in the peripheral hearing organ originate from the properties of the haircell-neuron synaps as revealed by their temperature dependency. In order to verify this hypothesis a model experiment is set up. The model consists of programming on an analog computer the equations describing the reaction kinetics from the frogs myoneural junction. A model neuron is attached to the synapsmodel in which two independent noise sources are incorporated. This noise addition serves to simulate the stochastic behavior of the transmitter release in the synaps resulting in a fluctuating generator potential and independently thereof to reflect the varying threshold of the nerve fiber. The reaction rate constants in the synaptic model were modified with respect to the original ones in order to get a coincidence of in vivo- and model results. The compound model primarily is used to simulate the quite different synchronization between the auditory nerve fibers occurring during intensity changes and during changes of the stimulus repetition rate. These results were known to be different in the animal experiments and were also generated by the model. It is shown clearly that neither synaptic noise alone nor membrane noise alone can account for the observations made in the animal experiments. Therefore a combination of both types of noise is used in this model. The model experiment also visualizes that amplitude changes for compound AP's during adaptation can be explained in toto by a decreasing synchronization, i.e. the broadening of the latency distribution function for the nerve fibers.     

Free-field unmasking response characteristics of frog auditory nerve fibers: comparison with the responses of midbrain auditory neurons

Previous studies in the inferior colliculus have shown that spatial separation of signal and noise sources improves signal detection. In this study, we investigated the free-field unmasking response properties of single fibers in the auditory nerve--these were compared to those of inferior colliculus neurons under the same experimental conditions to test the hypothesis that central processing confers advantages for signal detection in the presence of spatially separated noise. For each neuron, we determined the detection threshold for a probe at the unit's best azimuth under three conditions: (1) by itself, (2) when a masker at a constant level was also presented at the unit's best azimuth, and (3) when the masker was positioned at different azimuths. We found that, on average, maskers presented at a unit's best azimuth elevated the probe detection threshold by 4.22 dB in the auditory nerve and 10.97 dB in the inferior colliculus. Angular separation of probe and masker sources systematically reduced the masking effect. The maximum masking release was on average 2.90 dB for auditory nerve fibers and 9.40 dB for inferior colliculus units. These results support the working hypothesis, suggesting that central processing contributes to the stronger free-field unmasking in the inferior colliculus.     

Fast negative feedback enables mammalian auditory nerve fibers to encode a wide dynamic range of sound intensities

Mammalian auditory nerve fibers (ANF) are remarkable for being able to encode a 40 dB, or hundred fold, range of sound pressure levels into their firing rate. Most of the fibers are very sensitive and raise their quiescent spike rate by a small amount for a faint sound at auditory threshold. Then as the sound intensity is increased, they slowly increase their spike rate, with some fibers going up as high as ～300 Hz. In this way mammals are able to combine sensitivity and wide dynamic range. They are also able to discern sounds embedded within background noise. ANF receive efferent feedback, which suggests that the fibers are readjusted according to the background noise in order to maximize the information content of their auditory spike trains. Inner hair cells activate currents in the unmyelinated distal dendrites of ANF where sound intensity is rate-coded into action potentials. We model this spike generator compartment as an attenuator that employs fast negative feedback. Input current induces rapid and proportional leak currents. This way ANF are able to have a linear frequency to input current (f-I) curve that has a wide dynamic range. The ANF spike generator remains very sensitive to threshold currents, but efferent feedback is able to lower its gain in response to noise.     

Dopamine transporter is essential for the maintenance of spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation

Dopamine, a neurotransmitter released by the lateral olivocochlear efferents, has been shown tonically to inhibit the spontaneous and sound-evoked activity of auditory nerve fibres. This permanent inhibition probably requires the presence of an efficient transporter to remove dopamine from the synaptic cleft. Here, we report that the dopamine transporter is located in the lateral efferent fibres both below the inner hair cells and in the inner spiral bundle. Perilymphatic perfusion of the dopamine transporter inhibitors nomifensine and N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine into the cochlea reduced the spontaneous neural noise and the sound-evoked compound action potential of the auditory nerve in a dose-dependent manner, leading to both neural responses being completely abolished. We observed no significant change in cochlear responses generated by sensory hair cells (cochlear microphonic, summating potential, distortion products otoacoustic emissions) or in the endocochlear potential reflecting the functional state of the stria vascularis. This is consistent with a selective action of dopamine transporter inhibitors on auditory nerve activity. Capillary electrophoresis with laser-induced fluorescence (EC-LIF) measurements showed that nomifensine-induced inhibition of auditory nerve responses was due to increased extracellular dopamine levels in the cochlea. Altogether, these results show that the dopamine transporter is essential for maintaining the spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation.     

Spike-Threshold Adaptation Predicted by Membrane Potential Dynamics In Vivo

Neurons encode information in sequences of spikes, which are triggered when their membrane potential crosses a threshold. In vivo, the spiking threshold displays large variability suggesting that threshold dynamics have a profound influence on how the combined input of a neuron is encoded in the spiking. Threshold variability could be explained by adaptation to the membrane potential. However, it could also be the case that most threshold variability reflects noise and processes other than threshold adaptation. Here, we investigated threshold variation in auditory neurons responses recorded in vivo in barn owls. We found that spike threshold is quantitatively predicted by a model in which the threshold adapts, tracking the membrane potential at a short timescale. As a result, in these neurons, slow voltage fluctuations do not contribute to spiking because they are filtered by threshold adaptation. More importantly, these neurons can only respond to input spikes arriving together on a millisecond timescale. These results demonstrate that fast adaptation to the membrane potential captures spike threshold variability in vivo.     

On the choice of noise for the analysis of the peripheral auditory system

The cross-correlation between output and input of a system containing nonlinearities, when that system is stimulated with Gaussian white noise, is a good estimate of the linear properties of the system. In practice, however, when sequences of pseudonoise are used, great errors may be introduced in the estimate of the linear part depending on the properties of the noise. This consideration assumes special importance in the analysis of the linear properties of the peripheral auditory system, where the rectifying properties of the haircells constitute a second order nonlinearity. To explore this problem, a simple model has been designed, consisting of a second order nonlinearity without memory and sandwiched between two bandpass filters. Different types of pseudonoise are used as input whereupon it is shown that noise based on binary m-sequences, which is commonly used in noise generators, will yield totally incorrect information about this system. Somewhat better results are achieved with other types of noise. By using inverse-repeat sequences the results are greatly improved. Furthermore, certain anomalies obtained in the analysis of responses from single fibers in the auditory nerve are viewed in the light of the present results. The theoretical analysis of these anomalies reveals some information about the organization of the peripheral auditory system. For example, the possibility of the existence of a second bandpass filter in the auditory periphery seems to be excluded.     

Physiological characteristics of the tympanic organ in noctuoid moths

Summary We show the variations in the spike activity of both auditory receptors inSpodoptera frugiperda, Mocis latipes, Ascalapha odorata (Noctuidae),Maenas jussiae andEmpyreuma pugione (Arctiidae) immediately after 45 ms and 5 s acoustic stimuli at different intensities. The frequency of the applied stimuli was 34 kHz forE. pugione and 20 kHz for the other species. The electrical activity of the auditory receptors was recorded at the tympanic nerve with a stainless steel hook electrode. When the 45 ms pulses cease there is an afterdischarge from both auditory receptors in all the species. The number of spikes in the afterdischarge activity of both receptor cells (A₁ and A₂) shows a linear relation with stimulus intensity (Table 1). This number increases monotonically with increments in stimulus intensity, except for the A₁ cell activity inE. pugione, which decreases at intensities higher than 55 dB (Fig. 1). There are significant species-specific differences in the slope values of the number of spikes in the afterdischarge of both auditory receptors. After a 5 s stimulusM. latipes andM. jussiae show a rapid recovery of the standard spontaneous A₁-cell discharge level. Poststimulus A₁-cell spike activity inS. frugiperda shows a silent period, the duration of which increases with stimulus intensity (Fig. 3).E. pugione andA. odorata show such a silent period after low and moderately intense stimuli, but at high intensities the post-stimulus activity exceeds the pre-stimulus spontaneous discharge (Fig. 3). We demonstrate statistically that these variations cannot be explained by the random fluctuations of the standard spontaneous discharge. They are thus considered a silent and a rebound period respectively (Fig. 5). The presence and duration of either type of period seem to depend on the magnitude of the response to the acoustic stimulus. They thus seem related to the adaptation rate and the previously suggested existence of peripheral inhibitory interaction between the auditory receptors.     

Immediate and Delayed Cochlear Neuropathy after Noise Exposure in Pubescent Mice

Moderate acoustic overexposure in adult rodents is known to cause acute loss of synapses on sensory inner hair cells (IHCs) and delayed degeneration of the auditory nerve, despite the completely reversible temporary threshold shift (TTS) and morphologically intact hair cells. Our objective was to determine whether a cochlear synaptopathy followed by neuropathy occurs after noise exposure in pubescence, and to define neuropathic versus non-neuropathic noise levels for pubescent mice. While exposing 6 week old CBA/CaJ mice to 8-16 kHz bandpass noise for 2 hrs, we defined 97 dB sound pressure level (SPL) as the threshold for this particular type of neuropathic exposure associated with TTS, and 94 dB SPL as the highest non-neuropathic noise level associated with TTS. Exposure to 100 dB SPL caused permanent threshold shift although exposure of 16 week old mice to the same noise is reported to cause only TTS. Amplitude of wave I of the auditory brainstem response, which reflects the summed activity of the cochlear nerve, was complemented by synaptic ribbon counts in IHCs using confocal microscopy, and by stereological counts of peripheral axons and cell bodies of the cochlear nerve from 24 hours to 16 months post exposure. Mice exposed to neuropathic noise demonstrated immediate cochlear synaptopathy by 24 hours post exposure, and delayed neurodegeneration characterized by axonal retraction at 8 months, and spiral ganglion cell loss at 8-16 months post exposure. Although the damage was initially limited to the cochlear base, it progressed to also involve the cochlear apex by 8 months post exposure. Our data demonstrate a fine line between neuropathic and non-neuropathic noise levels associated with TTS in the pubescent cochlea.     

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.     

Analytical theory for extracellular electrical stimulation of nerve with focal electrodes. II. Passive myelinated axon.

The cable model of a passive, myelinated fiber is derived using the theory of electromagnetic propagation in periodic structures. The cable may be excited by an intracellular source or by an arbitrary, time-varying, applied extracellular field. When the cable is stimulated by a distant source, its properties are qualitatively similar to an unmyelinated fiber. Under these conditions relative threshold is proportional to the cube of the source distance and inversely proportional to the square of the fiber diameter. Electrical parameters of the model are chosen where possible, from mammalian peripheral nerve and anatomic parameters from cat auditory nerve. Several anatomic representations of the paranodal region are analyzed for their effects on the length and time constants of the fibers. Sensitivity of the model to parameter changes is studied. The linear model reliably predicts the effects of fiber size and electrode-fiber separation on threshold of cat dorsal column fibers to extracellular electrical stimulation.     

A statistical analyzer for optic nerve messages

A statistical mathematical model of the discharge in a single optic nerve fiber is proposed, based on a discharge with intervals between impulses distributed independently according to a gamma distribution ("gamma discharge"). A light stimulus distorts the time axis of this discharge according to a "frequency function" which is characteristic of the stimulus. A linear filter is described which calculates the likelihood of a certain stimulus when the nerve fiber message is fed into it. This filter forms the basis of theoretical nerve message analyzers for three visual experiments: (a) The detection of the occurrence of a flash of light of known intensity and time of occurrence, (b) the detection of the time of occurrence of a flash of known intensity, and (c) The estimation of the intensity of a flash occurring at a known time. Possible neural mechanisms in the brain for analyzing optic nerve messages, based on the above mathematical models, are suggested. Changes of excitability or discharge frequency correspond to the output of the likelihood filter. Any such mechanism must be sufficiently plastic to have a response matched to each expected stimuus for most efficient vision near threshold.     

Fast and slow effects of medial olivocochlear efferent activity in humans

Background

The medial olivocochlear (MOC) pathway modulates basilar membrane motion and auditory nerve activity on both a fast (10–100 ms) and a slow (10–100 s) time scale in guinea pigs. The slow MOC modulation of cochlear activity is postulated to aide in protection against acoustic trauma. However in humans, the existence and functional roles of slow MOC effects remain unexplored.

Methodology/Principal Findings

By employing contralateral noise at moderate to high levels (68 and 83 dB SPL) as an MOC reflex elicitor, and spontaneous otoacoustic emissions (SOAEs) as a non-invasive probe of the cochlea, we demonstrated MOC modulation of human cochlear output both on a fast and a slow time scale, analogous to the fast and slow MOC efferent effects observed on basilar membrane vibration and auditory nerve activity in guinea pigs. The magnitude of slow effects was minimal compared with that of fast effects. Consistent with basilar membrane and auditory nerve activity data, SOAE level was reduced by both fast and slow MOC effects, whereas SOAE frequency was elevated by fast and reduced by slow MOC effects. The magnitudes of fast and slow effects on SOAE level were positively correlated.

Conclusions/Significance

Contralateral noise up to 83 dB SPL elicited minimal yet significant changes in both SOAE level and frequency on a slow time scale, consistent with a high threshold or small magnitude of slow MOC effects in humans.