An iterative deconvolution model to extract the temporal firing properties of the auditory nerve fibers in human eCAPs.
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ABSTRACT:
SUBMITTER: Dong Y
PROVIDER: S-EPMC8374234 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Auditory nerve fibers (ANFs) exhibit a range of spontaneous firing rates (SRs) that are inversely correlated with threshold for sounds. To probe the underlying mechanisms and time course of SR differentiation during cochlear maturation, loose-patch extracellular recordings were made from ANF dendrites using acutely excised rat cochlear preparations of different ages after hearing onset. Diversification of SRs occurred mostly between the second and the third postnatal week. Statistical properties of ANF spike trains showed developmental changes that approach adult-like features in older preparations. Comparison with intracellularly recorded EPSCs revealed that most properties of ANF spike trains derive from the characteristics of presynaptic transmitter release. Pharmacological tests and waveform analysis showed that endogenous firing produces some fraction of ANF spikes, accounting for their unusual properties; the endogenous firing diminishes gradually during maturation. Paired recordings showed that ANFs contacting the same inner hair cell could have different SRs, with no correlation in their spike timing. SIGNIFICANCE STATEMENT:The inner hair cell (IHC)/auditory nerve fiber (ANF) synapse is the first synapse of the auditory pathway. Remarkably, each IHC is the sole partner of 10-30 ANFs with a range of spontaneous firing rates (SRs). Low and high SR ANFs respond to sound differently, and both are important for encoding sound information across varying acoustical environments. Here we demonstrate SR diversification after hearing onset by afferent recordings in acutely excised rat cochlear preparations. We describe developmental changes in spike train statistics and endogenous firing in immature ANFs. Dual afferent recordings provide the first direct evidence that fibers with different SRs contact the same IHCs and do not show correlated spike timing at rest. These results lay the groundwork for understanding the differential sensitivity of ANFs to acoustic trauma.
| S-EPMC5059429 | biostudies-literature
Project description:People suffering from age-related hearing loss typically present with deficits in temporal processing tasks. Temporal processing deficits have also been shown in single-unit studies at the level of the auditory brainstem, midbrain, and cortex of aged animals. In this study, we explored whether temporal coding is already affected at the level of the input to the central auditory system. Single-unit auditory nerve fiber recordings were obtained from 41 Mongolian gerbils of either sex, divided between young, middle-aged, and old gerbils. Temporal coding quality was evaluated as vector strength in response to tones at best frequency, and by constructing shuffled and cross-stimulus autocorrelograms, and reverse correlations, from responses to 1 s noise bursts at 10-30 dB sensation level (dB above threshold). At comparable sensation levels, all measures showed that temporal coding was not altered in auditory nerve fibers of aging gerbils. Furthermore, both temporal fine structure and envelope coding remained unaffected. However, spontaneous rates were decreased in aging gerbils. Importantly, despite elevated pure tone thresholds, the frequency tuning of auditory nerve fibers was not affected. These results suggest that age-related temporal coding deficits arise more centrally, possibly due to a loss of auditory nerve fibers (or their peripheral synapses) but not due to qualitative changes in the responses of remaining auditory nerve fibers. The reduced spontaneous rate and elevated thresholds, but normal frequency tuning, of aged auditory nerve fibers can be explained by the well known reduction of endocochlear potential due to strial dysfunction in aged gerbils.SIGNIFICANCE STATEMENT As our society ages, age-related hearing deficits become ever more prevalent. Apart from decreased hearing sensitivity, elderly people often suffer from a reduced ability to communicate in daily settings, which is thought to be caused by known age-related deficits in auditory temporal processing. The current study demonstrated, using several different stimuli and analysis techniques, that these putative temporal processing deficits are not apparent in responses of single-unit auditory nerve fibers of quiet-aged gerbils. This suggests that age-related temporal processing deficits may develop more central to the auditory nerve, possibly due to a reduced population of active auditory nerve fibers, which will be of importance for the development of treatments for age-related hearing disorders.
| S-EPMC6948943 | biostudies-literature
Project description:Spiral ganglion neurons (SGNs) and the associated components of the auditory nerve are primary carriers of auditory information from hair cells to the brain. Loss of SGNs occurs with many pathological conditions, resulting in permanent sensorineural hearing loss. Neural stem/progenitors (NSPs) have been well-characterized in several locations of adult brain and retina. However, it is unclear whether NSPs are present in the adult auditory nerve. Here we examined the self-renewal potential of the adult auditory nerve using ouabain application as a well-established mouse model of acute SGN injury. The observed increase in cell proliferation, alteration in enchromatin/heterochromatin ratio and down-regulation of histone deacetylase expression in glial cells suggest that the quiescent glial cells convert to an activated state after SGN degeneration. This was further confirmed by global gene expression analysis of injured auditory nerves, which showed up-regulation of numerous neurogenesis- and/or development-associated genes shortly after ouabain exposure. These genes include molecular markers commonly used for the identification of NSPs. Under a strict culture regimen, auditory nerve-derived cells of adult mouse ears gave rise to neurospheres, suggesting that multipotent NSPs are present in adult cochlear nerve. Neurosphere assays on Sox2 transgenic mice revealed that Sox2+ glial cells are the source for NSPs. Our data also showed that acute injury or hypoxia enhances neurosphere formation. Taken together, our study revealed that glial cells of adult cochlea exhibit several NSP characteristics, and hence these mature non-neuronal cells may be important targets for promoting self-repair of degenerative auditory nerves. Auditory nerves were removed from the temporal bones of adult CBA/CaJ mice, aged 8 to 12 weeks. Tissues were either collected and used directly as the tissue samples or dissociated and used for the cell culture samples. Dissociated auditory nerve cells were propagated and grown to full confluency (5-7 days), constituting the cultured cell samples. For neurosphere samples, growth medium was changed to neurosphere formation medium and the cells were cultured for an additional 12 days. All samples were prepared in triplicate (n=3).
2015-04-29 | E-GEOD-65249 | biostudies-arrayexpress
Project description:The processing characteristics of neurons in the central auditory system are directly shaped by and reflect the statistics of natural acoustic environments, but the principles that govern the relationship between natural sound ensembles and observed responses in neurophysiological studies remain unclear. In particular, accumulating evidence suggests the presence of a code based on sustained neural firing rates, where central auditory neurons exhibit strong, persistent responses to their preferred stimuli. Such a strategy can indicate the presence of ongoing sounds, is involved in parsing complex auditory scenes, and may play a role in matching neural dynamics to varying time scales in acoustic signals. In this paper, we describe a computational framework for exploring the influence of a code based on sustained firing rates on the shape of the spectro-temporal receptive field (STRF), a linear kernel that maps a spectro-temporal acoustic stimulus to the instantaneous firing rate of a central auditory neuron. We demonstrate the emergence of richly structured STRFs that capture the structure of natural sounds over a wide range of timescales, and show how the emergent ensembles resemble those commonly reported in physiological studies. Furthermore, we compare ensembles that optimize a sustained firing code with one that optimizes a sparse code, another widely considered coding strategy, and suggest how the resulting population responses are not mutually exclusive. Finally, we demonstrate how the emergent ensembles contour the high-energy spectro-temporal modulations of natural sounds, forming a discriminative representation that captures the full range of modulation statistics that characterize natural sound ensembles. These findings have direct implications for our understanding of how sensory systems encode the informative components of natural stimuli and potentially facilitate multi-sensory integration.
| S-EPMC3610626 | biostudies-literature
Project description:Spiral ganglion neurons (SGNs) and the associated components of the auditory nerve are primary carriers of auditory information from hair cells to the brain. Loss of SGNs occurs with many pathological conditions, resulting in permanent sensorineural hearing loss. Neural stem/progenitors (NSPs) have been well-characterized in several locations of adult brain and retina. However, it is unclear whether NSPs are present in the adult auditory nerve. Here we examined the self-renewal potential of the adult auditory nerve using ouabain application as a well-established mouse model of acute SGN injury. The observed increase in cell proliferation, alteration in enchromatin/heterochromatin ratio and down-regulation of histone deacetylase expression in glial cells suggest that the quiescent glial cells convert to an activated state after SGN degeneration. This was further confirmed by global gene expression analysis of injured auditory nerves, which showed up-regulation of numerous neurogenesis- and/or development-associated genes shortly after ouabain exposure. These genes include molecular markers commonly used for the identification of NSPs. Under a strict culture regimen, auditory nerve-derived cells of adult mouse ears gave rise to neurospheres, suggesting that multipotent NSPs are present in adult cochlear nerve. Neurosphere assays on Sox2 transgenic mice revealed that Sox2+ glial cells are the source for NSPs. Our data also showed that acute injury or hypoxia enhances neurosphere formation. Taken together, our study revealed that glial cells of adult cochlea exhibit several NSP characteristics, and hence these mature non-neuronal cells may be important targets for promoting self-repair of degenerative auditory nerves.
2015-04-29 | GSE65249 | GEO
Project description:Most auditory prostheses use modulated electric pulse trains to excite the auditory nerve. There are, however, scant data regarding the effects of pulse trains on auditory nerve fiber (ANF) responses across the duration of such stimuli. We examined how temporal ANF properties changed with level and pulse rate across 300-ms pulse trains. Four measures were examined: (1) first-spike latency, (2) interspike interval (ISI), (3) vector strength (VS), and (4) Fano factor (FF, an index of the temporal variability of responsiveness). Data were obtained using 250-, 1,000-, and 5,000-pulse/s stimuli. First-spike latency decreased with increasing spike rate, with relatively small decrements observed for 5,000-pulse/s trains, presumably reflecting integration. ISIs to low-rate (250 pulse/s) trains were strongly locked to the stimuli, whereas ISIs evoked with 5,000-pulse/s trains were dominated by refractory and adaptation effects. Across time, VS decreased for low-rate trains but not for 5,000-pulse/s stimuli. At relatively high spike rates (>200 spike/s), VS values for 5,000-pulse/s trains were lower than those obtained with 250-pulse/s stimuli (even after accounting for the smaller periods of the 5,000-pulse/s stimuli), indicating a desynchronizing effect of high-rate stimuli. FF measures also indicated a desynchronizing effect of high-rate trains. Across a wide range of response rates, FF underwent relatively fast increases (i.e., within 100 ms) for 5,000-pulse/s stimuli. With a few exceptions, ISI, VS, and FF measures approached asymptotic values within the 300-ms duration of the low- and high-rate trains. These findings may have implications for designs of cochlear implant stimulus protocols, understanding electrically evoked compound action potentials, and interpretation of neural measures obtained at central nuclei, which depend on understanding the output of the auditory nerve.
| S-EPMC2536806 | biostudies-other
Project description:Songbirds learn to sing much as humans learn to speak. In zebra finches, one of the premier songbird models, males learn to sing for later courtship through a multistep learning process during the developmental period. They first listen to and memorize the song of a tutor (normally their father) during the sensory learning period. Then, in the subsequent sensory-motor learning phase (with large overlap), they match their vocalizations to the memorized tutor song via auditory feedback and develop their own unique songs, which they maintain throughout their lives. Previous studies have suggested that memories of tutor songs are shaped in the caudomedial nidopallium (NCM) of the brain, which is analogous to the mammalian higher auditory cortex. Isolation during development, which extends the sensory learning period in males, alters song preference in adult females, and NCM inactivation decreases song preference. However, the development of neurophysiological properties of neurons in this area and the effect of isolation on these neurons have not yet been explained. Here, we performed whole-cell patch-clamp recording on NCM neurons from juvenile zebra finches during the sensory learning period, 20, 40, or 60 days post-hatching (DPH) and examined their neurophysiological properties. In contrast to previous reports in adult NCM neurons, the majority of NCM neurons of juvenile zebra finches showed spontaneous firing with or without burst firing patterns, and the percentage of neurons that fired increased in the middle of the sensory learning period (40 DPH) and then decreased at the end (60 DPH) in both males and females. We further found that auditory isolation from tutor songs alters developmental changes in the proportions of firing neurons both in males and females, and also changes those of burst neurons differently between males that sing and females that do not. Taken together, these findings suggest that NCM neurons develop their neurophysiological properties depending on auditory experiences during the sensory song learning period, which underlies memory formation for song learning in males and song discrimination in females.
| S-EPMC7578418 | biostudies-literature
Project description:Background: Multi-compartment cable models of auditory nerve fibers have been developed to assist in the improvement of cochlear implants. With the advancement of computational technology and the results obtained from in vivo and in vitro experiments, these models have evolved to incorporate a considerable degree of morphological and physiological details. They have also been combined with three-dimensional volume conduction models of the cochlea to simulate neural responses to electrical stimulation. However, no specific rules have been provided on choosing the appropriate cable model, and most models adopted in recent studies were chosen without a specific reason or by inheritance. Methods: Three of the most cited biophysical multi-compartment cable models of the human auditory nerve, i.e., Rattay et al. (2001b), Briaire and Frijns (2005), and Smit et al. (2010), were implemented in this study. Several properties of single fibers were compared among the three models, including threshold, conduction velocity, action potential shape, latency, refractory properties, as well as stochastic and temporal behaviors. Experimental results regarding these properties were also included as a reference for comparison. Results: For monophasic single-pulse stimulation, the ratio of anodic vs. cathodic thresholds in all models was within the experimental range despite a much larger ratio in the model by Briaire and Frijns. For biphasic pulse-train stimulation, thresholds as a function of both pulse rate and pulse duration differed between the models, but none matched the experimental observations even coarsely. Similarly, for all other properties including the conduction velocity, action potential shape, and latency, the models presented different outcomes and not all of them fell within the range observed in experiments. Conclusions: While all three models presented similar values in certain single fiber properties to those obtained in experiments, none matched all experimental observations satisfactorily. In particular, the adaptation and temporal integration behaviors were completely missing in all models. Further extensions and analyses are required to explain and simulate realistic auditory nerve fiber responses to electrical stimulation.
| S-EPMC6848226 | biostudies-literature
Project description:Information processing in the brain requires reliable synaptic transmission. High reliability at specialized auditory nerve synapses in the cochlear nucleus results from many release sites (N), high probability of neurotransmitter release (Pr), and large quantal size (Q). However, high Pr also causes auditory nerve synapses to depress strongly when activated at normal rates for a prolonged period, which reduces fidelity. We studied how synapses are influenced by prolonged activity by exposing mice to constant, nondamaging noise and found that auditory nerve synapses changed to facilitating, reflecting low Pr. For mice returned to quiet, synapses recovered to normal depression, suggesting that these changes are a homeostatic response to activity. Two additional properties, Q and average excitatory postsynaptic current (EPSC) amplitude, were unaffected by noise rearing, suggesting that the number of release sites (N) must increase to compensate for decreased Pr. These changes in N and Pr were confirmed physiologically using the integration method. Furthermore, consistent with increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta, larger profiles in electron micrographs, and more release sites per profile. In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, auditory nerve synapses regulate excitability through an activity-dependent, homeostatic mechanism, which could have major effects on all downstream processing. Our results also suggest that noise-exposed bushy cells would remain hyperexcitable for a period after returning to normal quiet conditions, which could have perceptual consequences.
| S-EPMC4443347 | biostudies-literature
Project description:The ventral tegmental area (VTA) is one of the main brain regions harboring dopaminergic (DA) neurons, and plays important roles in reinforcement and motivation. Recent studies have indicated that DA neurons not only respond to rewarding stimuli, but also to noxious stimuli. Furthermore, VTA DA neurons undergo plasticity during chronic pain. Lateral and medial VTA neurons project to different brain areas, and have been characterized via their distinct electrophysiological properties. In this study, we characterized electrophysiological properties of lateral and medial VTA DA neurons using DAT-cre reporter mice, and examined their plasticity during neuropathic pain states. We observed various DA subpopulations in both the lateral and medial VTA, as defined by action potential firing patterns, independently of synaptic inputs. Our results demonstrated that lateral and medial VTA DA neurons undergo differential plasticity after peripheral nerve injury that leads to neuropathic pain. However, these changes only reside in specific DA subpopulations. This study suggests that lateral and medial VTA DA neurons are differentially affected during neuropathic pain conditions, and emphasizes the importance of subpopulation specificity when targeting VTA DA neurons for treatment of neuropathic pain.
| S-EPMC6827252 | biostudies-literature