Noise Overexposure Alters Long-Term Somatosensory-Auditory Processing in the Dorsal Cochlear Nucleus--Possible Basis for Tinnitus-Related Hyperactivity?

The cochlear nucleus, the first central auditory structure, performs initial stimulus processing and segregation of information into parallel ascending pathways. It also receives nonauditory inputs. Here we show in vivo that responses of dorsal cochlear nucleus (DCN) principal neurons to sounds can change significantly depending on the presence or absence of inputs from the somatosensory dorsal column nucleus occurring before the onset of auditory stimuli. The effects range from short-term suppression of spikes lasting a few milliseconds at the onset of the stimulus to long-term increases or decreases in spike rate that last throughout the duration of an acoustic stimulus (up to several hundred milliseconds). The long-term effect requires only a single electrical stimulus pulse to initiate and seems to be similar to persistent activity reported in other parts of the brain. Among the DCN inhibitory interneurons, only the cartwheel cells show a long-term rate decrease that could account for the rate increases (but not the decreases) of DCN principal cells. Thus even at the earliest stages of auditory processing, the represented information is dependent on nonauditory context, in this case somatosensory events.

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Mechanisms Underlying Long-Term Synaptic Zinc Plasticity at Mouse Dorsal Cochlear Nucleus Glutamatergic Synapses

Journal of Neuroscience ◽

10.1523/jneurosci.0175-20.2020 ◽

2020 ◽

Vol 40 (26) ◽

pp. 4981-4996 ◽

Cited By ~ 2

Author(s):

Nathan W. Vogler ◽

Vincent M. Betti ◽

Jacob M. Goldberg ◽

Thanos Tzounopoulos

Keyword(s):

Cochlear Nucleus ◽

Dorsal Cochlear Nucleus ◽

Glutamatergic Synapses

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Expression and Localization of Kv1.1 and Kv3.1b Potassium Channels in the Cochlear Nucleus and Inferior Colliculus after Long-Term Auditory Deafferentation

Brain Sciences ◽

10.3390/brainsci10010035 ◽

2020 ◽

Vol 10 (1) ◽

pp. 35 ◽

Cited By ~ 2

Author(s):

Clara Poveda ◽

Maria Valero ◽

Marianny Pernia ◽

Juan Alvarado ◽

David Ryugo ◽

...

Keyword(s):

Potassium Channels ◽

Protein Expression ◽

Inferior Colliculus ◽

Auditory Processing ◽

Cochlear Nucleus ◽

Auditory Pathway ◽

Cellular Mechanisms ◽

Auditory Deprivation ◽

Central Auditory Neurons

Deafness affects the expression and distribution of voltage-dependent potassium channels (Kvs) of central auditory neurons in the short-term, i.e., hours to days, but the consequences in the expression of Kvs after long-term deafness remain unknown. We tested expression and distribution of Kv1.1 and Kv3.1b, key for auditory processing, in the rat cochlear nucleus (CN), and in the inferior colliculus (IC), at 1, 15 and 90 days after mechanical lesion of the cochlea, using a combination of qRT-PCR and Western blot in the whole CN, along with semi-quantitative immunocytochemistry in the AVCN, where the role of both Kvs in the control of excitability for accurate auditory timing signal processing is well established. Neither Kv1.1/Kv3.1b mRNA or protein expression changed significantly in the CN between 1 and 15 days after deafness. At 90 days post-lesion, however, mRNA and protein expression for both Kvs increased, suggesting that regulation of Kv1.1 and Kv3.1b expression is part of cellular mechanisms for long-term adaptation to auditory deprivation in the CN. Consistent with these findings, immunocytochemistry showed increased labeling intensity for both Kvs in the AVCN at day 90 after cochlear lesion. This increase argues that up-regulation of Kv1.1 and Kv3.1b in AVCN neurons may be required to adapt intrinsic excitability to altered input over the long term after auditory deprivation. Contrary to these findings in the CN, expression levels of Kv1.1 and Kv3.1b in the IC did not undergo major changes after cochlear lesion. In particular, there was no evidence of long-term up-regulation of either Kv1.1 or Kv3.1b, supporting that such post-lesion adaptive mechanism may not be needed in the IC. These results reveal that post-lesion adaptations do not necessarily involve stereotyped plastic mechanisms along the entire auditory pathway.

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Single-neuron recordings from unanesthetized mouse dorsal cochlear nucleus

Journal of Neurophysiology ◽

10.1152/jn.00427.2011 ◽

2012 ◽

Vol 107 (3) ◽

pp. 824-835 ◽

Cited By ~ 12

Author(s):

Wei-Li Diana Ma ◽

Stephan D. Brenowitz

Keyword(s):

Cochlear Nucleus ◽

Single Neuron ◽

Dorsal Cochlear Nucleus ◽

Future Studies ◽

Auditory Neuroscience ◽

Neuronal Mechanisms ◽

Auditory Physiology ◽

Complex Spikes

Because of the availability of disease and genetic models, the mouse has become a valuable species for auditory neuroscience that will facilitate long-term goals of understanding neuronal mechanisms underlying the perception and processing of sounds. The goal of this study was to define the basic sound-evoked response properties of single neurons in the mouse dorsal cochlear nucleus (DCN). Neurons producing complex spikes were distinguished as cartwheel cells (CWCs), and other neurons were classified according to the response map scheme previously developed in DCN. Similar to observations in other rodent species, neurons of the mouse DCN exhibit relatively little sound-driven inhibition. As a result, type III was the most commonly observed response. Our findings are generally consistent with the model of DCN function that has been developed in the cat and the gerbil, suggesting that this in vivo mouse preparation will be a useful tool for future studies of auditory physiology.

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Saturation of long-term potentiation in the dorsal cochlear nucleus and its pharmacological reversal in an experimental model of tinnitus

Experimental Neurology ◽

10.1016/j.expneurol.2017.02.011 ◽

2017 ◽

Vol 292 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Thomas Tagoe ◽

Daniel Deeping ◽

Martine Hamann

Keyword(s):

Experimental Model ◽

Cochlear Nucleus ◽

Long Term Potentiation ◽

Dorsal Cochlear Nucleus ◽

Term Potentiation

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Saturation of long-term potentiation in the dorsal cochlear nucleus and its pharmacological reversal in an experimental model of tinnitus

10.26226/morressier.5b31ec742afeeb001345b3d6 ◽

2018 ◽

Author(s):

Thomas Tagoe

Keyword(s):

Experimental Model ◽

Cochlear Nucleus ◽

Long Term Potentiation ◽

Dorsal Cochlear Nucleus ◽

Term Potentiation

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Temporal and Frequency Characteristics of Cartwheel Cells in the Dorsal Cochlear Nucleus of the Awake Mouse

Journal of Neurophysiology ◽

10.1152/jn.01356.2006 ◽

2007 ◽

Vol 98 (2) ◽

pp. 744-756 ◽

Cited By ~ 33

Author(s):

Christine V. Portfors ◽

Patrick D. Roberts

Keyword(s):

Auditory Processing ◽

Cochlear Nucleus ◽

Auditory Nerve ◽

Active Role ◽

Auditory Pathway ◽

Dorsal Cochlear Nucleus ◽

Central Auditory Processing ◽

Complex Frequency ◽

Principal Cells ◽

Cartwheel Cells

The dorsal cochlear nucleus (DCN) is an initial site of central auditory processing and also the first site of multisensory convergence in the auditory pathway. The auditory nerve imparts a tonotopic frequency organization on the responses of principal cells in the DCN. Cartwheel cells modify the responses of principal cells, but they do not receive direct auditory nerve input. This study shows that cartwheel cells respond well to tonal stimuli in the awake mouse and they have a well-defined characteristic frequency that corresponds to the tonotopic organization of the DCN. The auditory responses of cartwheel cells exhibit complex spectrotemporal responses to tones, with excitation and inhibition modulating the firing patterns in both frequency and time after onset of the stimulus. Temporal responses to best-frequency tones are highly variable between cartwheel cells, but a simple model is used to unify this variability as differences in the timing of synaptic currents. Cartwheel cell responses to two-tone stimuli show that interactions from different frequencies affect the output of cartwheel cells. The results suggest that at this primary auditory structure, processing of sound at one frequency can be modified by sounds of different frequency. These complex frequency and temporal interactions in cartwheel cells suggest that these neurons play an active role in basic sound processing.

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In Vitro Studies of Neuromodulation and Plasticity in the Dorsal Cochlear Nucleus

The Oxford Handbook of the Auditory Brainstem ◽

10.1093/oxfordhb/9780190849061.013.5 ◽

2018 ◽

pp. 122-142 ◽

Cited By ~ 1

Author(s):

Laurence O. Trussell

Keyword(s):

Synaptic Plasticity ◽

Auditory Processing ◽

Cochlear Nucleus ◽

Cell Types ◽

Auditory Pathway ◽

Dorsal Cochlear Nucleus ◽

Membrane Properties ◽

Auditory Input ◽

Dynamic Tuning

The dorsal cochlear nucleus (DCN), a division of the cochlear nuclear complex, has been the subject of intense interest for its role in auditory processing and hearing disorders. The tonotopic layout of DCN principal cells and the refinement of processing of auditory signals by interneurons are together thought to permit encoding of sound source elevation. However, the many cell types and complex connectivity of the DCN suggest more diverse functions than localization. A prominent non-auditory input to the DCN has been proposed to assist in such functions as orienting to sounds of interest, detecting moving sounds, or cancelling self-generated sounds. Synaptic plasticity in the DCN may be essential for dynamic tuning of non-auditory input. Indeed, long-term changes in synaptic or membrane properties could underlie tinnitus, which is associated with hyperactivity in the DCN in some animal models. Finally, the DCN is invested with wide-ranging neuromodulatory mechanisms, suggesting that changes in the behavioral state of animals associated with such neuromodulatory systems might alter sensory processing at the earliest stages of the auditory pathway. This review will focus on studies that have utilized the in vitro brain slice approach to identify basic mechanisms of synaptic plasticity and neuromodulation in the DCN.

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Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus

Journal of Neurophysiology ◽

10.1152/jn.00270.2016 ◽

2017 ◽

Vol 117 (3) ◽

pp. 1229-1238 ◽

Cited By ~ 11

Author(s):

Roxana A. Stefanescu ◽

Susan E. Shore

Keyword(s):

Spontaneous Activity ◽

Cochlear Nucleus ◽

Acetylcholine Receptors ◽

Dorsal Cochlear Nucleus ◽

Muscarinic Acetylcholine Receptors ◽

Fusiform Cell ◽

Baseline Activity ◽

Stimulus Timing

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N-methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology. NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology.

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Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

American Journal of Audiology ◽

10.1044/2020_aja-20-00018 ◽

2020 ◽

Vol 29 (4) ◽

pp. 710-727

Author(s):

Beula M. Magimairaj ◽

Naveen K. Nagaraj ◽

Alexander V. Sergeev ◽

Natalie J. Benafield

Keyword(s):

Auditory Processing ◽

Short Term Memory ◽

Group Differences ◽

Long Term Memory ◽

Short Term ◽

Significant Group ◽

Term Memory ◽

Memory And Attention ◽

Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

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