scholarly journals Synaptic transmission between end bulbs of Held and bushy cells in the cochlear nucleus of mice with a mutation in Otoferlin

2014 ◽  
Vol 112 (12) ◽  
pp. 3173-3188 ◽  
Author(s):  
Samantha Wright ◽  
Youngdeok Hwang ◽  
Donata Oertel
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Calcium Binding ◽  
Otoacoustic Emissions ◽  
Nerve Fibers ◽  
Mutant Mice ◽  
Synaptic Current ◽  
Cross Sectional ◽  
Distortion Product ◽  
Bushy Cells

Mice that carry a mutation in a calcium binding domain of Otoferlin, the putative calcium sensor at hair cell synapses, have normal distortion product otoacoustic emissions (DPOAEs), but auditory brain stem responses (ABRs) are absent. In mutant mice mechanotransduction is normal but transmission of acoustic information to the auditory pathway is blocked even before the onset of hearing. The cross-sectional area of the auditory nerve of mutant mice is reduced by 54%, and the volume of ventral cochlear nuclei is reduced by 46% relative to hearing control mice. While the tonotopic organization was not detectably changed in mutant mice, the axons to end bulbs of Held and the end bulbs themselves were smaller. In mutant mice bushy cells in the anteroventral cochlear nucleus (aVCN) have the electrophysiological hallmarks of control cells. Spontaneous miniature excitatory postsynaptic currents (EPSCs) occur with similar frequencies and have similar shapes in deaf as in hearing animals, but they are 24% larger in deaf mice. Bushy cells in deaf mutant mice are contacted by ∼2.6 auditory nerve fibers compared with ∼2.0 in hearing control mice. Furthermore, each fiber delivers more synaptic current, on average 4.8 nA compared with 3.4 nA, in deaf versus hearing control mice. The quantal content of evoked EPSCs is not different between mutant and control mice; the increase in synaptic current delivered in mutant mice is accounted for by the increased response to the size of the quanta. Although responses to shocks presented at long intervals are larger in mutant mice, they depress more rapidly than in hearing control mice.

Convergence of auditory nerve fibers onto bushy cells in the ventral cochlear nucleus: implications of a computational model

1993 ◽  
Vol 70 (6) ◽  
pp. 2562-2583 ◽  
Author(s):  
J. S. Rothman ◽  
E. D. Young ◽  
P. B. Manis
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Full Range ◽  
Nerve Fibers ◽  
Membrane Properties ◽  
Delayed Rectifier ◽  
Current Clamp ◽  
Synaptic Inputs ◽  
Ventral Cochlear Nucleus ◽  
Bushy Cells

1. Convergence of auditory nerve (AN) fibers onto bushy cells of the ventral cochlear nucleus (VCN) was investigated with a model that describes the electrical membrane properties of these cells. The model consists of a single compartment, representing the soma, and includes three voltage-sensitive ion channels (fast sodium, delayed-rectifier-like potassium, and low-threshold potassium). These three channels have characteristics derived from voltage clamp data of VCN bushy cells. The model also contains a leakage channel, membrane capacitance, and synaptic inputs. The model accurately reproduces the membrane rectification seen in current clamp studies of bushy cells, as well as their unique current clamp responses. 2. In this study, the number and synaptic strength of excitatory AN inputs to the model were varied to investigate the relationship between input convergence parameters and response characteristics. From 1 to 20 excitatory synaptic inputs were applied through channels in parallel with the voltage-gated channels. Each synapse was driven by an independent AN spike train; spike arrivals produced brief (approximately 0.5 ms) conductance increases. The number (NS) and conductance (AE) of these inputs were systematically varied. The input spike trains were generated as a renewal point process that accurately models characteristics of AN fibers (refractoriness, adaptation, onset latency, irregularity of discharge, and phase locking). Adaptation characteristics of both high and low spontaneous rate (SR) AN fibers were simulated. 3. As NS and AE vary over the ranges 1–20 and 3–80 nS, respectively, the full range of response types seen in VCN bushy cells are produced by the model, with AN inputs typical of high-SR AN fibers. These include primarylike (PL), primarylike-with-notch (Pri-N), and onset-L (On-L). In addition, Onset responses, whose association with bushy cells in uncertain, and “dip” responses, which are not seen in the VCN, are produced. Dip responses occur with large NS and/or AE, and are due to depolarization block. When the AN inputs have the adaptation characteristics of low-SR AN fibers, PL--but not Pri-N or On-L responses--are produced. This suggests that neurons showing Pri-N and On-L responses must receive high-SR AN inputs. 4. The regularity of discharge of the model is compared with that of VCN bushy cells, using a measure derived from the mean and standard deviation of interspike intervals. Regularity is an important constraint on the model because the regularity of VCN bushy cells is the same as that of their AN inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Reducing Auditory Nerve Excitability by Acute Antagonism of Ca2+-Permeable AMPA Receptors

2021 ◽  
Vol 13 ◽  
Author(s):  
Amit Walia ◽  
Choongheon Lee ◽  
Jared Hartsock ◽  
Shawn S. Goodman ◽  
Roland Dolle ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Ampa Receptors ◽  
Auditory Nerve ◽  
Otoacoustic Emissions ◽  
Nerve Fibers ◽  
Glutamate Excitotoxicity ◽  
Blood Levels ◽  
Systemic Delivery ◽  
Cochlear Function ◽  
Distortion Product

Hearing depends on glutamatergic synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs are tetramers, where inclusion of the GluA2 subunit reduces overall channel conductance and Ca2+ permeability. Cochlear afferent synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs) contain the AMPAR subunits GluA2, 3, and 4. However, the tetrameric complement of cochlear AMPAR subunits is not known. It was recently shown in mice that chronic intracochlear delivery of IEM-1460, an antagonist selective for GluA2-lacking AMPARs [also known as Ca2+-permeable AMPARs (CP-AMPARs)], before, during, and after acoustic overexposure prevented both the trauma to ANF synapses and the ensuing reduction of cochlear nerve activity in response to sound. Surprisingly, baseline measurements of cochlear function before exposure were unaffected by chronic intracochlear delivery of IEM-1460. This suggested that cochlear afferent synapses contain GluA2-lacking CP-AMPARs alongside GluA2-containing Ca2+-impermeable AMPA receptors (CI-AMPARs), and that the former can be antagonized for protection while the latter remain conductive. Here, we investigated hearing function in the guinea pig during acute local or systemic delivery of CP-AMPAR antagonists. Acute intracochlear delivery of IEM-1460 or systemic delivery of IEM-1460 or IEM-1925 reduced the amplitude of the ANF compound action potential (CAP) significantly, for all tone levels and frequencies, by > 50% without affecting CAP thresholds or distortion product otoacoustic emissions (DPOAE). Following systemic dosing, IEM-1460 levels in cochlear perilymph were ~ 30% of blood levels, on average, consistent with pharmacokinetic properties predicting permeation of the compounds into the brain and ear. Both compounds were metabolically stable with half-lives >5 h in vitro, and elimination half-lives in vivo of 118 min (IEM-1460) and 68 min (IEM-1925). Heart rate monitoring and off-target binding assays suggest an enhanced safety profile for IEM-1925 over IEM-1460. Compound potency on CAP reduction (IC50 ~ 73 μM IEM-1460) was consistent with a mixture of GluA2-lacking and GluA2-containing AMPARs. These data strongly imply that cochlear afferent synapses of the guinea pig contain GluA2-lacking CP-AMPARs. We propose these CP-AMPARs may be acutely antagonized with systemic dosing, to protect from glutamate excitotoxicity, while transmission at GluA2-containing AMPARs persists to mediate hearing during the protection.

Encoding timing and intensity in the ventral cochlear nucleus of the cat

1986 ◽  
Vol 56 (2) ◽  
pp. 261-286 ◽  
Author(s):  
W. S. Rhode ◽  
P. H. Smith
Keyword(s):  
Firing Rate ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Cell Types ◽  
Nerve Fibers ◽  
Frequency Selectivity ◽  
Firing Rates ◽  
Ventral Cochlear Nucleus ◽  
Auditory Nerve Fibers ◽  
Different Cell Types

Physiological response properties of neurons in the ventral cochlear nucleus have a variety of features that are substantially different from the stereotypical auditory nerve responses that serve as the principal source of activation for these neurons. These emergent features are the result of the varying distribution of auditory nerve inputs on the soma and dendrites of the various cell types within the nucleus; the intrinsic membrane characteristics of the various cell types causing different responses to the same input in different cell types; and secondary excitatory and inhibitory inputs to different cell types. Well-isolated units were recorded with high-impedance glass microelectrodes, both intracellularly and extracellularly. Units were characterized by their temporal response to short tones, rate vs. intensity relation, and response areas. The principal response patterns were onset, chopper, and primary-like. Onset units are characterized by a well-timed first spike in response to tones at the characteristic frequency. For frequencies less than 1 kHz, onset units can entrain to the stimulus frequency with greater precision than their auditory nerve inputs. This implies that onset units receive converging inputs from a number of auditory nerve fibers. Onset units are divided into three subcategories, OC, OL, and OI. OC units have extraordinarily wide dynamic ranges and low-frequency selectivity. Some are capable of sustaining firing rates of 800 spikes/s at high intensities. They have the smallest standard deviation and coefficient of variation of the first spike latency of any cells in the cochlear nuclei. OC units are candidates for encoding intensity. OI and OL units differ from OC units in that they have dynamic ranges and frequency selectivity ranges much like those of auditory nerve fibers. They differ from one another in their steady-state firing rates; OI units fire mainly at the onset of a tone. OI units also differ from OL units in that they prefer frequency sweeps in the low to high direction. Primary-like-with-notch (PLN) units also respond to tones with a well-timed first spike. They differ from onset cells in that the onset peak is not always as precise as the spontaneous rate is higher. A comparison of spontaneous firing rate and saturation firing rate of PLN units with auditory nerve fibers suggest that PLN units receive one to four auditory nerve fiber inputs. Chopper units fire in a sustained regular manner when they are excited by sound.(ABSTRACT TRUNCATED AT 400 WORDS)

Frequency Tuning and Spontaneous Activity in the Auditory Nerve and Cochlear Nucleus Magnocellularis of the Barn Owl Tyto alba

1997 ◽  
Vol 77 (1) ◽  
pp. 364-377 ◽  
Author(s):  
Christine Köppl
Keyword(s):  
Response Latency ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Frequency Tuning ◽  
Barn Owl ◽  
Nerve Fibers ◽  
Spontaneous Discharge ◽  
Tyto Alba ◽  
Nucleus Magnocellularis ◽  
Auditory Nerve Fibers

Köppl, Christine. Frequency tuning and spontaneous activity in the auditory nerve and cochlear nucleus magnocellularis of the barn owl Tyto alba. J. Neurophysiol. 77: 364–377, 1997. Single-unit recordings were obtained from the brain stem of the barn owl at the level of entrance of the auditory nerve. Auditory nerve and nucleus magnocellularis units were distinguished by physiological criteria, with the use of the response latency to clicks, the spontaneous discharge rate, and the pattern of characteristic frequencies encountered along an electrode track. The response latency to click stimulation decreased in a logarithmic fashion with increasing characteristic frequency for both auditory nerve and nucleus magnocellularis units. The average difference between these populations was 0.4–0.55 ms. The most sensitive thresholds were ∼0 dB SPL and varied little between 0.5 and 9 kHz. Frequency-threshold curves showed the simple V shape that is typical for birds, with no indication of a low-frequency tail. Frequency selectivity increased in a gradual, power-law fashion with increasing characteristic frequency. There was no reflection of the unusual and greatly expanded mapping of higher frequencies on the basilar papilla of the owl. This observation is contrary to the equal-distance hypothesis that relates frequency selectivity to the spatial respresentation in the cochlea. On the basis of spontaneous rates and/or sensitivity there was no evidence for distinct subpopulations of auditory nerve fibers, such as the well-known type I afferent response classes in mammals. On the whole, barn owl auditory nerve physiology conformed entirely to the typical patterns seen in other bird species. The only exception was a remarkably small spread of thresholds at any one frequency, this being only 10–15 dB in individual owls. Average spontaneous rate was 72.2 spikes/s in the auditory nerve and 219.4 spikes/s for nucleus magnocellularis. This large difference, together with the known properties of endbulb-of-Held synapses, suggests a convergence of ∼2–4 auditory nerve fibers onto one nucleus magnocellularis neuron. Some auditory nerve fibers as well as nucleus magnocellularis units showed a quasiperiodic spontaneous discharge with preferred intervals in the time-interval histogram. This phenomenon was observed at frequencies as high as 4.7 kHz.

scholarly journals Hearing Performance in the Follicular-Luteal Phase of the Menstrual Cycle

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Seyede Faranak Emami ◽  
Nasrin Gohari ◽  
Hossein Ramezani ◽  
Mariam Borzouei
Keyword(s):  
Menstrual Cycle ◽  
Otoacoustic Emissions ◽  
Luteal Phase ◽  
Pure Tone Audiometry ◽  
Nerve Fibers ◽  
Follicular Phase ◽  
Auditory Brainstem Responses ◽  
Auditory Function ◽  
Distortion Product ◽  
Excitatory Action

Introduction. Estrogen has a protective role on auditory function. It may have an excitatory action on auditory nerve fibers and can have a neuroprotective effect. Progesterone has a mainly inhibitory action on the central nervous system, which may balance the mainly excitatory action of estrogen. Objective. To determine changes in hearing performance with pure tone audiometry (PTA), tympanometry, distortion product otoacoustic emissions (DPOAEs), and auditory brainstem responses (ABR) as hormonal changes occur from follicular to luteal phase. Materials and Methods. Twenty healthy female volunteers (age 19 ± 30 years) with normal menstrual cycle and without any hearing problems are included in this case-control study. Hearing evaluation was performed on the 13th day of the menstrual cycle (follicular phase) and then on the 22nd day (luteal phase). Results. All of the participants had normal results in follicular phase. In luteal phase, four cases showed abnormalities as follows: reduced hearing thresholds 250 Hz (mean= 15 dBHL), increased amplitudes of DPOAE (mean= 3 dBspl), decreased middle ear pressure (mean= -110 dapa), and delayed ABR interpeak latencies (mean of IPLs I-III= 0.4 and mean of IPLs III-V= 0.6 ms). Conclusions. In some women, changing of ovarian hormones may induce fluctuating hearing and increased progesterone in luteal phase can lead to abnormal outcomes in auditory function. However, elevated estrogen modifies its consequences in follicular phase.

R446 – Rostral Cochlear Nucleus Changes After Cochlear Ablation

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P194-P194 ◽  
Author(s):  
Kyle Robinson ◽  
Donald A Godfrey ◽  
Matthew A. Godfrey
Keyword(s):  
Auditory Processing ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
High Performance ◽  
Nerve Fibers ◽  
Average Concentration ◽  
Gamma Aminobutyric Acid ◽  
Freeze Dried ◽  
Concentration Changes ◽  
Temporal Bones

Problem Identification of neurotransmitter concentration changes occurring in the rostral anterior ventral cochlear nucleus (AVCN) following transection of the auditory nerve within the cochlea. Methods Chinchillas with cochlear ablations, as well as sham-lesioned chinchillas, were euthanized at times ranging from 3 to 84 days post ablation. Both temporal bones and brains were saved. Temporal bones were fixed, embedded in paraffin and sectioned to document the completeness of the cochlear lesion. Brain portions containing the cochlear nuclei were frozen-sectioned, and sections were freeze dried. Freeze-dried sections were microdissected into samples of AVCN for high performance liquid chromatography (HPLC) assay of 12 amino acid concentrations. Results The average concentration of glutamate, the most likely neurotransmitter of auditory nerve fibers, declined in the lesioned-side rostral AVCN by about 25% at 15 days. This decrease was maintained through 31 days post ablation and became bilateral at 83 days. There was no decrease in the adjacent granular region. Larger lesioned-side decreases, approaching 50%, were found more caudally in the AVCN at 31 days post ablation. The average concentration of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) decreased bilaterally by 15–25% at 3 through 15 days post ablation. Conclusion The degeneration of the central portion of the auditory nerve following mechanical ablation of the cochlea is accompanied by decreases of glutamate concentration on the lesioned side but bilateral decreases of GABA in the rostral part of the AVCN. These decreases were smaller than those reported previously for the posteroventral cochlear nucleus (PVCN). However, changes more caudally in AVCN approach those found in PVCN. Significance Our results are consistent with other evidence that damage to the cochlea leads to neurotransmitter changes in the central auditory system. The smaller changes in AVCN than in PVCN may correlate with different types of auditory processing in these two regions. Support The American Tinnitus Association and the University of Toledo Foundation.

Frequency extent of two-tone facilitation in onset units in the ventral cochlear nucleus

1996 ◽  
Vol 75 (1) ◽  
pp. 380-395 ◽  
Author(s):  
D. Jiang ◽  
A. R. Palmer ◽  
I. M. Winter
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Inhibitory Input ◽  
Ventral Cochlear Nucleus ◽  
Narrow Region ◽  
Morphological Studies ◽  
Wide Range ◽  
Auditory Nerve Fibers

1. The frequency threshold curves (FTCs) of 91 single units in the cochlear nucleus of the anesthetized guinea pig were measured using a conventional single-tone paradigm and a two-tone paradigm designed to elucidate the frequency extent of two-tone facilitation in onset units (On). Units were classified according to existing classification schemes into primary-like (n = 3), chopper (n = 23), and three onset groups: OnI (n = 12), OnC (n = 29), and OnL (n = 24). Histological reconstructions show onset units to be widely distributed within the ventral cochlear nucleus in a manner generally consistent with its tonotopic organization. 2. The FTCs of onset units differed in their minimum thresholds, the steepness of their high- and low-frequency cutoffs, and their sharpness of tuning as quantified by the quality factor at 10 dB (Q10dB) above best frequency (BF) threshold values. There was considerable overlap in the sharpness of tuning between onset units and auditory nerve fibers, as indicated by the distribution of Q10dB values in the octave around 10 kHz: onset units had Q10dB values of 3.56 +/- 1.38 (SD), compared with 6.3 +/- 2.48 for auditory nerve fibers. The tuning of chopper units was similar to that of auditory nerve fibers (5.52 +/- 1.46). 3. Seventy-five percent of onset units showed some degree of facilitation (a threshold reduction) when their FTCs were measured in the presence of BF tones 4 dB below BF threshold. The frequency extent of such facilitation was variable, with a maximum of 6 octaves around the BF. In extreme cases facilitation could be measured when the BF tone was as low as 30 dB below BF threshold. 4. In 17% of onset units, suppressive effects were evident, as shown by noncontiguous frequency regions of facilitation. These suppressive effects might be a reflection either of suppression in the auditory nerve input or of a direct inhibitory input to the onset units. The strength of this effect suggests that inhibition is a likely explanation, consistent with the finding in previous morphological studies of profuse synapses with pleomorphic vesicles on multipolar cells. 5. FTCs of chopper and primary-like units measured in the presence of BF tones showed little facilitation. The facilitation that was observed in chopper units was confined to a narrow region around BF and disappeared when the facilitatory tone was lowered to 4 dB below BF threshold. 6. These data support the hypothesis that onset units, but not chopper or primary-like units, receive excitatory inputs from auditory nerve fibers with a wide range of BFs. However, the frequency range of facilitation and the magnitude of the threshold facilitation varied from unit to unit, suggesting that the off-BF inputs from auditory nerve fibers are not evenly distributed or equally effective in all units.

Neuronal circuits associated with the output of the dorsal cochlear nucleus through fusiform cells

1994 ◽  
Vol 71 (3) ◽  
pp. 914-930 ◽  
Author(s):  
S. Zhang ◽  
D. Oertel
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Nerve Fibers ◽  
Dorsal Cochlear Nucleus ◽  
Resting Potential ◽  
Temporal Association ◽  
Common Source ◽  
Excitatory Postsynaptic Potential ◽  
Current Voltage ◽  
Synaptic Responses

1. Intracellular recordings were made from 21 anatomically identified fusiform cells in the dorsal cochlear nucleus (DCN) of mice in slices. The aim of the experiments was to dissect the synaptic responses to shocks of the auditory nerve to correlate functional characteristics with the different classes of synaptic inputs. 2. When depolarized from rest (-57 +/- 5 mV) with current pulses, fusiform cells fired regular, overshooting action potentials that were followed by two undershoots. The frequency of firing increased with the strength of injected current by between 100 and 300 spikes/s/nA. The current-voltage relationship rectified between 10 and 15 mV below the resting potential. The slopes of current-voltage relationships of fusiform cells in the range between the resting potential and 10 mV hyperpolarization indicated an average input resistance of 86 +/- 37 M omega. 3. In each of the labeled fusiform cells frequent, spontaneous inhibitory postsynaptic potentials (IPSPs) were recorded singly or in bursts. Some, but not all, IPSPs were preceded by a slowly rising excitatory postsynaptic potential (EPSP). The temporal association of spontaneous EPSPs and IPSPs suggests that they are driven by a common source, possibly granule cells. 4. Shocks to the auditory nerve evoked synaptic responses consisting of early (1 to approximately 10 ms) and late (approximately 10 to 100 ms) components. 6,7-Dinitroquinoxaline-2,3-dione (DNQX) at 20 to 40 microM eliminated all detectable excitation and all late IPSPs. Late bursts of IPSPs, therefore, are mediated through a polysynaptic pathway that includes a DNQX-sensitive stage. Strong shocks to the nerve root elicited single monosynaptic IPSPs, indicating that inhibitory interneurons have processes close to the auditory nerve. Strychnine at 0.5 microM eliminated all detectable inhibition. 6. Cuts through the posteroventral cochlear nucleus (PVCN), which severed the descending branches of auditory nerve fibers, eliminated early EPSPs and IPSPs leaving late, slowly rising EPSPs and bursts of IPSPs in responses to shocks of the auditory nerve. Late, slowly rising EPSPs and bursts of IPSPs, as well as monosynaptic IPSPs, could also be evoked by stimulating the anteroventral cochlear nucleus (AVCN). 7. Focal applications of glutamate evoked excitation and inhibition from many parts of a slice, with patterns varying among cells, indicating that fusiform cells receive inputs through several groups of interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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