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Nature Reviews. Neurology Mar 2016Tinnitus is a phantom auditory sensation that reduces quality of life for millions of people worldwide, and for which there is no medical cure. Most cases of tinnitus... (Review)
Review
Tinnitus is a phantom auditory sensation that reduces quality of life for millions of people worldwide, and for which there is no medical cure. Most cases of tinnitus are associated with hearing loss caused by ageing or noise exposure. Exposure to loud recreational sound is common among the young, and this group are at increasing risk of developing tinnitus. Head or neck injuries can also trigger the development of tinnitus, as altered somatosensory input can affect auditory pathways and lead to tinnitus or modulate its intensity. Emotional and attentional state could be involved in the development and maintenance of tinnitus via top-down mechanisms. Thus, military personnel in combat are particularly at risk owing to combined risk factors (hearing loss, somatosensory system disturbances and emotional stress). Animal model studies have identified tinnitus-associated neural changes that commence at the cochlear nucleus and extend to the auditory cortex and other brain regions. Maladaptive neural plasticity seems to underlie these changes: it results in increased spontaneous firing rates and synchrony among neurons in central auditory structures, possibly generating the phantom percept. This Review highlights the links between animal and human studies, and discusses several therapeutic approaches that have been developed to target the neuroplastic changes underlying tinnitus.
Topics: Animals; Auditory Cortex; Auditory Pathways; Cochlear Nucleus; Humans; Neuronal Plasticity; Noise; Tinnitus; Treatment Outcome
PubMed: 26868680
DOI: 10.1038/nrneurol.2016.12 -
Scientific Reports Mar 2021Multisensory integration of auditory and tactile information occurs already at the level of the cochlear nucleus. Rodents use their whiskers for tactile perception to...
Multisensory integration of auditory and tactile information occurs already at the level of the cochlear nucleus. Rodents use their whiskers for tactile perception to guide them in their exploration of the world. As nocturnal animals with relatively poor vision, audiotactile interactions are of great importance for this species. Here, the influence of whisker deflections on sound-evoked spiking in the cochlear nucleus was investigated in vivo in anesthetized mice. Multichannel, silicon-probe electrophysiological recordings were obtained from both the dorsal and ventral cochlear nucleus. Whisker deflections evoked an increased spiking activity in fusiform cells of the dorsal cochlear nucleus and t-stellate cells in ventral cochlear nucleus, whereas bushy cells in the ventral cochlear nucleus showed a more variable response. The response to broadband noise stimulation increased in fusiform cells and primary-like bushy cells when the sound stimulation was preceded (~ 20 ms) by whisker stimulation. Multi-sensory integration of auditory and whisker input can thus occur already in this early brainstem nucleus, emphasizing the importance of early integration of auditory and somatosensory information.
Topics: Acoustic Stimulation; Animals; Cochlear Nucleus; Electric Stimulation; Evoked Potentials, Somatosensory; Male; Mice; Mice, Inbred C57BL; Neural Inhibition; Neurons; Sensation; Vibrissae
PubMed: 33767295
DOI: 10.1038/s41598-021-86236-9 -
Hearing Research Nov 2022The cochlear efferent system comprises multiple populations of brainstem neurons whose axons project to the cochlea, and whose responses to acoustic stimuli lead to... (Review)
Review
The cochlear efferent system comprises multiple populations of brainstem neurons whose axons project to the cochlea, and whose responses to acoustic stimuli lead to regulation of auditory sensitivity. The major groups of efferent neurons are found in the superior olivary complex and are likely activated by neurons of the cochlear nucleus, thus forming a simple reflex pathway back to the cochlea. The peripheral actions of only one of these efferent cell types has been well described. Moreover, the efferent neurons are not well understood at the cellular- and circuit-levels. For example, ample demonstration of descending projections to efferent neurons raises the question of whether these additional inputs constitute a mechanism for modulation of relay function or instead play a more prominent role in driving the efferent response. Related to this is the question of synaptic plasticity at these synapses, which has the potential to differentially scale the degree of efferent activation across time, depending on the input pathway. This review will explore central nervous system aspects of the efferent system, the physiological properties of the neurons, their synaptic inputs, their modulation, and the effects of efferent axon collaterals within the brainstem.
Topics: Acoustic Stimulation; Auditory Pathways; Brain Stem; Cochlea; Cochlear Nucleus; Efferent Pathways; Neurons, Efferent; Olivary Nucleus
PubMed: 35606211
DOI: 10.1016/j.heares.2022.108516 -
BMC Biology May 2022The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of...
BACKGROUND
The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca/Calmodulin kinase 2 α (CaMKII α)-positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus.
RESULTS
Mice were exposed to loud noise (9-11kHz, 90dBSPL, 1h, followed by 2h of silence), and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded 2 days before and 2 weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKII α+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKII α+ DCN units decrease tinnitus-like responses (p = 3e -3, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKII α-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKII α-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise exposure (n = 6 experimental and 6 control mice).
CONCLUSION
We found that lowering DCN activity in mice displaying tinnitus-related behavior reduces tinnitus, but lowering DCN activity during noise exposure does not prevent noise-induced tinnitus. Our results suggest that CaMKII α-positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.
Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cochlear Nucleus; Evoked Potentials, Auditory, Brain Stem; Mice; Perception; Tinnitus
PubMed: 35550106
DOI: 10.1186/s12915-022-01288-1 -
Hearing Research Nov 2011This chapter reviews evidence for functional connections of the somatosensory and auditory systems at the very lowest levels of the nervous system. Neural inputs from... (Review)
Review
This chapter reviews evidence for functional connections of the somatosensory and auditory systems at the very lowest levels of the nervous system. Neural inputs from the dosal root and trigeminal ganglia, as well as their brain stem nuclei, cuneate, gracillis and trigeminal, terminate in the cochlear nuclei. Terminations are primarily in the shell regions surrounding the cochlear nuclei but some terminals are found in the magnocellular regions of cochlear nucleus. The effects of stimulating these inputs on multisensory integration are shown as short and long-term, both suppressive and enhancing. Evidence that these projections are glutamatergic and are altered after cochlear damage is provided in the light of probable influences on the modulation and generation of tinnitus.
Topics: Acoustic Stimulation; Animals; Auditory Pathways; Cochlear Nucleus; Evoked Potentials, Auditory; Glutamic Acid; Humans; Neuronal Plasticity; Somatosensory Cortex; Time Factors; Tinnitus
PubMed: 21620940
DOI: 10.1016/j.heares.2011.05.001 -
International Journal of Molecular... Jan 2023Mammals have a dorsal cochlear nucleus (DCN), which is thought to be a cerebellum-like structure with similar features in terms of structure and microcircuitry to the... (Review)
Review
Mammals have a dorsal cochlear nucleus (DCN), which is thought to be a cerebellum-like structure with similar features in terms of structure and microcircuitry to the cerebellum. Both the DCN and cerebellum perform their functions depending on synaptic and neuronal networks mediated by various glutamate receptors. Kainate receptors (KARs) are one class of the glutamate receptor family and are strongly expressed in the hippocampus, the cerebellum, and cerebellum-like structures. The cellular distribution and the potential role of KARs in the hippocampus have been extensively investigated. However, the cellular distribution and the potential role of KARs in cerebellum-like structures, including the DCN and cerebellum, are poorly understood. In this review, we summarize the similarity between the DCN and cerebellum at the levels of structure, circuitry, and cell type as well as the investigations referring to the expression patterns of KARs in the DCN and cerebellum according to previous studies. Recent studies on the role of KARs have shown that KARs mediate a bidirectional modulatory effect at parallel fiber (PF)-Purkinje cell (PC) synapses in the cerebellum, implying insights into their roles in cerebellum-like structures, including the DCN, that remain to be explored in the coming years.
Topics: Animals; Cochlear Nucleus; Receptors, Kainic Acid; Neurons; Axons; Synapses; Cerebellum; Mammals
PubMed: 36675230
DOI: 10.3390/ijms24021718 -
Progress in Brain Research 2007Somatic tinnitus is clinically observed modulation of the pitch and loudness of tinnitus by somatic stimulation. This phenomenon and the association of tinnitus with... (Review)
Review
Somatic tinnitus is clinically observed modulation of the pitch and loudness of tinnitus by somatic stimulation. This phenomenon and the association of tinnitus with somatic neural disorders indicate that neural connections between the somatosensory and auditory systems may play a role in tinnitus. Anatomical and physiological evidence supports these observations. The trigeminal and dorsal root ganglia relay afferent somatosensory information from the periphery to secondary sensory neurons in the brainstem, specifically, the spinal trigeminal nucleus and dorsal column nuclei, respectively. Each of these structures has been shown to send excitatory projections to the cochlear nucleus. Mossy fibers from the spinal trigeminal and dorsal column nuclei terminate in the granule cell domain while en passant boutons from the ganglia terminate in the granule cell domain and core region of the cochlear nucleus. Sources of these somatosensory-auditory projections are associated with proprioceptive and cutaneous, but not nociceptive, sensation. Single unit and evoked potential recordings in the dorsal cochlear nucleus indicate that these pathways are physiologically active. Stimulation of the dorsal column and the cervical dorsal root ganglia elicits short- and long-latency inhibition separated by a transient excitatory peak in DCN single units. Similarly, activation of the trigeminal ganglion elicits excitation in some DCN units and inhibition in others. Bimodal integration in the DCN is demonstrated by comparing responses to somatosensory and auditory stimulation alone with responses to paired somatosensory and auditory stimulation. The modulation of firing rate and synchrony in DCN neurons by somatatosensory input is physiological correlate of somatic tinnitus.
Topics: Animals; Cochlear Nucleus; Humans; Somatosensory Cortex; Tinnitus; Trigeminal Nerve
PubMed: 17956776
DOI: 10.1016/S0079-6123(07)66010-5 -
The Journal of Neuroscience : the... Feb 2016Tinnitus, the perception of phantom sounds, is thought to arise from increased neural synchrony, which facilitates perceptual binding and creates salient sensory...
UNLABELLED
Tinnitus, the perception of phantom sounds, is thought to arise from increased neural synchrony, which facilitates perceptual binding and creates salient sensory features in the absence of physical stimuli. In the auditory cortex, increased spontaneous cross-unit synchrony and single-unit bursting are de facto physiological correlates of tinnitus. However, it is unknown whether neurons in the dorsal cochlear nucleus (DCN), the putative tinnitus-induction site, exhibit increased synchrony. Using a temporary-threshold shift model and gap-prepulse inhibition of the acoustic startle to assess tinnitus, we recorded spontaneous activity from fusiform cells, the principle neurons of the DCN, in normal hearing, tinnitus, and non-tinnitus guinea pigs. Synchrony and bursting, as well as spontaneous firing rate (SFR), correlated with behavioral evidence of tinnitus, and increased synchrony and bursting were associated with SFR elevation. The presence of increased synchrony and bursting in DCN fusiform cells suggests that a neural code for phantom sounds emerges in this brainstem location and likely contributes to the formation of the tinnitus percept.
SIGNIFICANCE STATEMENT
Tinnitus, a phantom auditory percept, is encoded by pathological changes in the neural synchrony code of perceptual processing. Increased cross-unit synchrony and bursting have been linked to tinnitus in several higher auditory stations but not in fusiform cells of the dorsal cochlear nucleus (DCN), key brainstem neurons in tinnitus generation. Here, we demonstrate increased synchrony and bursting of fusiform cell spontaneous firing, which correlate with frequency-specific behavioral measures of tinnitus. Thus, the neural representation of tinnitus emerges early in auditory processing and likely drives its pathophysiology in higher structures.
Topics: Algorithms; Animals; Cochlear Nucleus; Electrophysiological Phenomena; Evoked Potentials, Auditory; Evoked Potentials, Auditory, Brain Stem; Female; Guinea Pigs; Models, Neurological; Noise; Reflex, Startle; Tinnitus
PubMed: 26865628
DOI: 10.1523/JNEUROSCI.3960-15.2016 -
Brain Research Nov 2012Tinnitus, the perception of a phantom sound, is a common consequence of damage to the auditory periphery. A major goal of tinnitus research is to find the loci of the... (Review)
Review
Tinnitus, the perception of a phantom sound, is a common consequence of damage to the auditory periphery. A major goal of tinnitus research is to find the loci of the neural changes that underlie the disorder. Crucial to this endeavor has been the development of an animal behavioral model of tinnitus, so that neural changes can be correlated with behavioral evidence of tinnitus. Three major lines of evidence implicate the dorsal cochlear nucleus (DCN) in tinnitus. First, elevated spontaneous activity in the DCN is correlated with peripheral damage and tinnitus. Second, there are somatosensory inputs to the DCN that can modulate spontaneous activity and might mediate the somatic-auditory interactions seen in tinnitus patients. Third, we have found a subpopulation of DCN neurons in the adult rat that express doublecortin, a plasticity-related protein. The expression of this protein may reflect a role of these neurons in the neural reorganization causing tinnitus. However, there is a problem in extending the findings in the rodent DCN to humans. Classic studies state that the structure of the primate DCN is quite different from that of rodents, with primates lacking granule cells, the recipients of somatosensory input. To address the possibility of major species differences in DCN organization, we compared Nissl-stained sections of the DCN in five different species. In contrast to earlier reports, our data suggest that the organization of the primate DCN is not dramatically different from that of the rodents, and validate the use of animal data in the study of tinnitus. This article is part of a Special Issue entitled: Tinnitus Neuroscience.
Topics: Animals; Cats; Chinchilla; Cochlear Nucleus; Doublecortin Protein; Humans; Immunohistochemistry; Macaca mulatta; Neuronal Plasticity; Rabbits; Rats; Tinnitus
PubMed: 22513100
DOI: 10.1016/j.brainres.2012.03.044 -
Hearing Research Mar 2018Models of the auditory brainstem have been an invaluable tool for testing hypotheses about auditory information processing and for highlighting the most important gaps...
Models of the auditory brainstem have been an invaluable tool for testing hypotheses about auditory information processing and for highlighting the most important gaps in the experimental literature. Due to the complexity of the auditory brainstem, and indeed most brain circuits, the dynamic behavior of the system may be difficult to predict without a detailed, biologically realistic computational model. Despite the sensitivity of models to their exact construction and parameters, most prior models of the cochlear nucleus have incorporated only a small subset of the known biological properties. This confounds the interpretation of modelling results and also limits the potential future uses of these models, which require a large effort to develop. To address these issues, we have developed a general purpose, biophysically detailed model of the cochlear nucleus for use both in testing hypotheses about cochlear nucleus function and also as an input to models of downstream auditory nuclei. The model implements conductance-based Hodgkin-Huxley representations of cells using a Python-based interface to the NEURON simulator. Our model incorporates most of the quantitatively characterized intrinsic cell properties, synaptic properties, and connectivity available in the literature, and also aims to reproduce the known response properties of the canonical cochlear nucleus cell types. Although we currently lack the empirical data to completely constrain this model, our intent is for the model to continue to incorporate new experimental results as they become available.
Topics: Acoustic Stimulation; Animals; Auditory Pathways; Cochlear Nucleus; Computer Simulation; Evoked Potentials, Auditory, Brain Stem; Hearing; Humans; Models, Neurological
PubMed: 29331233
DOI: 10.1016/j.heares.2017.12.017