Search Results (5)

Background/Objectives: Tinnitus and hyperacusis can occur together or in isolation, with hyperacusis being associated with tinnitus much more frequently than vice versa. This striking correlation between tinnitus and hyperacusis prevalence implies that there might be a common origin, such as (hidden) hearing loss, and possibly interrelated neural mechanisms in the pathological development of those two conditions. Here, we propose such interrelated pathological mechanisms. Methods: This is a theoretical work based solely on considerations and published data. Results: We propose a model localized in the dorsal cochlear nucleus (DCN) of the brainstem, based on classical mechanisms of Hebbian and associative plasticity known from classical conditioning. Specifically, our model proposes that hyperacusis results from the synaptic enhancement of cochlear input to the DCN, whereas chronic tinnitus results from the synaptic enhancement of somatosensory input to the DCN. Specific conditions leading to one or the other condition are discussed. Conclusions: Our model predicts that hearing loss leads to chronic tinnitus, while noise exposure (which may also cause hearing loss) leads to hyperacusis. We would like to emphasize that our aim with the proposed model is not to provide a self-contained theoretical construct, but to stimulate thought regarding possible pathological causes of tinnitus and hyperacusis that have not yet been investigated. Individual assumptions that cannot yet be substantiated by the existing literature are intended to provide impetus for future experimental studies. Full article

Serotonergic projections innervate both the dorsal and ventral cochlear nuclei; however, the electrophysiological consequences of serotonergic input in the ventral cochlear nucleus (VCN) remain incompletely understood. This study aimed to identify the serotonin receptor subtypes involved in serotonergic modulation of stellate cells in the mouse anteroventral cochlear nucleus (AVCN) and to determine the underlying ion channel mechanisms. Whole-cell patch-clamp recordings were performed in acute brain slices obtained from postnatal day 12–17 mice. Bath application of serotonin (25 µM) induced membrane depolarization (~5 mV) and increased action potential firing. Pharmacological experiments demonstrated that antagonists of 5-HT1A, 5-HT2A, and 5-HT2C receptors partially reversed the depolarization and reduced serotonin-induced inward currents, indicating that multiple receptor subtypes contribute to serotonergic excitation. Blockade of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with extracellular Cs⁺ suppressed approximately 95% of the serotonin-induced depolarization and inward current, implicating HCN channel-mediated Ih as a principal ionic mechanism. Serotonin significantly increased Ih amplitude. Analysis of steady-state activation revealed no statistically significant shift in V0.5; however, under near-resting membrane potential conditions, serotonin significantly reduced the slope factor of the activation curve, consistent with altered voltage sensitivity of Ih gating. Immunohistochemical analysis confirmed the presence of 5-HT1A, 5-HT2A, and 5-HT2C receptors in the AVCN. Together, these findings indicate that serotonergic excitation of AVCN stellate cells is mediated by coordinated activation of multiple 5-HT receptor subtypes and primarily involves modulation of HCN-dependent subthreshold membrane dynamics. Full article

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. Full article

Tinnitus, a common disease in the clinic, is associated with persistent pain and high costs to society. Several aspects of tinnitus, such as the pathophysiology mechanism, effective treatment, objective detection, etc., have not been elucidated. Any change in the auditory pathway can lead to tinnitus. At present, there is no clear and unified mechanism to explain tinnitus, and the hypotheses regarding its mechanism include auditory plasticity theory, cortical reorganization theory, dorsal cochlear nucleus hypothesis, etc. Current theories on the mechanism of tinnitus mainly focus on the abnormal activity of the central nervous system. Unfortunately, there is currently a lack of objective diagnostic methods for tinnitus. Developing a method that can detect tinnitus objectively is crucial, only in this way can we identify whether the patient really suffers from tinnitus in the case of cognitive impairment or medical disputes and the therapeutic effect of tinnitus. Electrophysiological investigations have prompted the development of an objective detection of tinnitus by potentials recorded in the auditory pathway. However, there is no objective indicator with sufficient sensitivity and specificity to diagnose tinnitus at present. Based on recent findings of studies with various methods, possible electrophysiological approaches to detect the presence of tinnitus have been summarized. We analyze the change of neural activity throughout the auditory pathway in tinnitus subjects and in patients with tinnitus of varying severity to find available parameters in these methods, which is helpful to further explore the feasibility of using electrophysiological methods for the objective detection of tinnitus. Full article

Many people are affected by tinnitus, a sensation of ringing in the ear despite the absence of external sound. Goshajinkigan (GJG) is one of the formulations of Japanese traditional herbal medicine and is prescribed for the palliative treatment of patients with tinnitus. Although GJG is clinically effective in these patients, its behavioral effects and the underlying neuroanatomical substrate have not been modeled in animals. We modeled tinnitus using salicylate-treated rats, demonstrated the effectiveness of GJG on tinnitus, and examined the underlying neuronal substrate with c-Fos expression. Intraperitoneal injection of sodium salicylate (400 mg/kg) into rats for three consecutive days significantly increased false positive scores, which were used to assess tinnitus behavior. When GJG was orally administered one hour after each salicylate injection, the increase in tinnitus behavior was suppressed. The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models. Full article