Characteristic alterations of gut microbiota and serum metabolites in patients with chronic tinnitus: a multi-omics analysis.

Chronic tinnitus is a central nervous system disorder. Currently, the effects of gut microbiota on tinnitus remain unexplored. To explore the connection between gut microbiota and tinnitus, we conducted 16S rRNA sequencing of fecal microbiota and serum metabolomic analysis in a cohort of 70 patients with tinnitus and 30 healthy volunteers.

Danshensu reduces neuronal excitability by enhancing potassium currents in bushy cells in the mouse cochlear nucleus.

Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative and neuroprotective effects are well-documented, the underlying mechanisms are poorly understood. In this study, we sought out to investigate if and how Danshensu modulates neuronal excitability and voltage-gated ionic currents in the central nervous system.

Resveratrol prevents hearing loss and a subregion specific- reduction of serotonin reuptake transporter induced by noise exposure in the central auditory system.

Prolonged or excessive exposure to noise can lead to hearing loss, tinnitus and hypersensitivity to sound. The effects of noise exposure on main excitatory and inhibitory neurotransmitter systems in auditory pathway have been extensively investigated. However, little is known about aberrant changes in neuromodulator systems caused by noise exposure.

Focusing on the Emerging Role of Kainate Receptors in the Dorsal Cochlear Nucleus (DCN) and Cerebellum.

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.

Electrically Evoked Auditory Brainstem Responses in Children Fitted with Hearing Aids Prior to Cochlear Implantation.

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs).

Outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates antibiotic-induced anxiety and depression-like behavior in mice.

Akkermansia muciniphila is present in the mucus layer of its host gut, and its outer membrane protein Amuc_1100 has a significant ameliorative effect on metabolic disorders and emotional memory aspects of enteritis, obesity, depression, and anxiety in the host. Antibiotics affect gut microbial composition, leading to imbalance and behavioral changes in the gut-brain axis, while probiotics have a protective effect against behavioral changes caused by gut flora disorders. In the present study, a depressed mouse model using a broad-spectrum cocktail mixture resulted in increased anxiety and depression-like behavior, decreased serum and hippocampal levels of 5-hydroxytryptamine (5-HT), and increased serum corticosterone (cort) levels.

Electrically evoked auditory brainstem responses in deaf patients with Mondini malformation during cochlear implantation.

Purpose: To investigate the auditory pathway functions in deaf patients with Mondini malformation using the electrically evoked auditory brainstem response (EABR) during cochlear implantation (CI).

Methods: A total of 58 patients with severe to profound sensorineural hearing loss (SNHL) were included in this study. Of these patients, 27 cases had Mondini malformation and 31 control cases had no inner ear malformations (IEMs).

The outer membrane protein Amuc_1100 of Akkermansia muciniphila alleviates the depression-like behavior of depressed mice induced by chronic stress.

Akkermansia muciniphila is a symbiotic intestinal bacterium with a high medicinal value. Amuc_1100 is the outer membrane protein of A. muciniphila and plays an important role in the interaction between A.

The outer membrane protein Amuc_1100 of promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling.

Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host.

Sodium salicylate enhances neural excitation via reducing GABAergic transmission in the dentate gyrus area of rat hippocampus in vivo.

Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation.

Resveratrol noncompetitively inhibits glycine receptor-mediated currents in neurons of rat central auditory neurons.

Resveratrol, a naturally occurring stilbene found in red wine, is known to modulate the activity of several types of ion channels and membrane receptors, including Ca, K, and Na ion channels. However, little is known about the effects of resveratrol on some important receptors, such as glycine receptors and GABA receptors, in the central nervous system (CNS). In the present study, the effects of resveratrol on glycine receptor or GABA receptor-mediated currents in cultured rat inferior colliculus (IC) and auditory cortex (AC) neurons were studied using whole-cell voltage-clamp recordings.

Cross-talk pattern between GABA- and glycine-receptors in CNS neurons is shaped by their relative expression levels.

GABA receptors (GABARs) and glycine receptors (GlyRs) are two principal inhibitory chloride ion channels in the central nervous system. The two receptors do not function independently but cross-talk to each other, i.e.

A Central Amygdala Input to the Parafascicular Nucleus Controls Comorbid Pain in Depression.

While comorbid pain in depression (CP) occurs at a high rate worldwide, the neural connections underlying the core symptoms of CP have yet to be elucidated. Here, we define a pathway whereby GABAergic neurons from the central nucleus of the amygdala (GABA) project to glutamatergic neurons in the parafascicular nucleus (Glu). These Glu neurons relay directly to neurons in the second somatosensory cortex (S2), a well-known area involved in pain signal processing.

Anatomy and Physiology of Metabotropic Glutamate Receptors in Mammalian and Avian Auditory System.

Glutamate, as the major excitatory neurotransmitter used in the vertebrate brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), which mediate fast and slow neuronal actions, respectively. mGluRs play important modulatory roles in many brain areas, forming potential targets for drugs developed to treat brain disorders. Here, we review studies on mGluRs in the mammalian and avian auditory system.

Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific.

Many studies have explored how neuromodulators affect synaptic function, yet little is known about how they modify computations at the microcircuit level. In the dorsal cochlear nucleus (DCN), a region that integrates auditory and multisensory inputs from two distinct pathways, serotonin (5-HT) enhances excitability of principal cells, predicting a generalized reduction in sensory thresholds. Surprisingly, we found that when looked at from the circuit level, 5-HT enhances signaling only from the multisensory input, while decreasing input from auditory fibers.

Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) is one of the first stations within the central auditory pathway where the basic computations underlying sound localization are initiated and heightened activity in the DCN may underlie central tinnitus. The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT), is associated with many distinct behavioral or cognitive states, and serotonergic fibers are concentrated in the DCN. However, it remains unclear what is the function of this dense input.

Interplay between low threshold voltage-gated K(+) channels and synaptic inhibition in neurons of the chicken nucleus laminaris along its frequency axis.

Central auditory neurons that localize sound in horizontal space have specialized intrinsic and synaptic cellular mechanisms to tightly control the threshold and timing for action potential generation. However, the critical interplay between intrinsic voltage-gated conductances and extrinsic synaptic conductances in determining neuronal output are not well understood. In chicken, neurons in the nucleus laminaris (NL) encode sound location using interaural time difference (ITD) as a cue.

Activation of synaptic group II metabotropic glutamate receptors induces long-term depression at GABAergic synapses in CNS neurons.

Metabotropic glutamate receptor (mGluR)-dependent homosynaptic long-term depression (LTD) has been studied extensively at glutamatergic synapses in the CNS. However, much less is known about heterosynaptic long-term plasticity induced by mGluRs at inhibitory synapses. Here we report that pharmacological or synaptic activation of group II mGluRs (mGluR II) induces LTD at GABAergic synapses without affecting the excitatory glutamatergic transmission in neurons of the chicken cochlear nucleus.

Two GABAA responses with distinct kinetics in a sound localization circuit.

The temporal characteristics and functional diversity of GABAergic inhibition are determined by the spatiotemporal neurotransmitter profile, intrinsic properties of GABAA receptors, and other factors. Here, we report two distinct GABAA responses and the underlying mechanisms in neurons of the chicken nucleus laminaris (NL), the first encoder of interaural time difference for sound localization in birds. The time course of the postsynaptic GABAA currents in NL neurons, recorded with whole-cell voltage clamp, differed between different characteristic frequency (CF) regions.

Development of GPCR modulation of GABAergic transmission in chicken nucleus laminaris neurons.

Neurons in the nucleus laminaris (NL) of birds act as coincidence detectors and encode interaural time difference to localize the sound source in the azimuth plane. GABAergic transmission in a number of CNS nuclei including the NL is subject to a dual modulation by presynaptic GABA(B) receptors (GABA(B)Rs) and metabotropic glutamate receptors (mGluRs). Here, using in vitro whole-cell patch clamp recordings from acute brain slices of the chick, we characterized the following important but unknown properties pertaining to such a dual modulation: (1) emergence of functional GABA synapses in NL neurons; (2) the temporal onset of neuromodulation mediated by GABA(B)Rs and mGluRs; and (3) the physiological conditions under which GABA(B)Rs and mGluRs are activated by endogenous transmitters.

Synaptic activity-induced Ca(2+) signaling in avian cochlear nucleus magnocellularis neurons.

Neurons of the avian cochlear nucleus magnocellularis (NM) receive glutamatergic inputs from the spiral ganglion cells via the auditory nerve and feedback GABAergic inputs primarily from the superior olivary nucleus. We investigated regulation of Ca(2+) signaling in NM neurons with ratiometric Ca(2+) imaging in chicken brain slices. Application of exogenous glutamate or GABA increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) in NM neurons.

Cross-talk between NMDA and GABA(A) receptors in cultured neurons of the rat inferior colliculus.

Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels, a process called cross-talk. The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABA(A) receptor) are important excitatory and inhibitory receptors in the central nervous system, respectively. Currently, cross-talk between the NMDA receptor and the GABA(A) receptor, particularly in the central auditory system, is not well understood.

Ambient GABA-activated tonic inhibition sharpens auditory coincidence detection via a depolarizing shunting mechanism.

Tonic inhibition mediated by extrasynaptic GABA(A) receptors (GABA(A)Rs) has emerged as a novel form of neural inhibition in the CNS. However, little is known about its presence and function in the auditory system. Using whole-cell recordings in brain slices, we identified a tonic current mediated by GABA(A)Rs containing the δ subunit in middle/high-characteristic-frequency neurons of the chicken nucleus laminaris, the first interaural time difference encoder that computes information for sound localization.

Control of a depolarizing GABAergic input in an auditory coincidence detection circuit.

Neurons in the chicken nucleus laminaris (NL), the third-order auditory neurons that detect the interaural time differences that enable animals to localize sounds in the horizontal plane, receive glutamatergic excitation from the cochlear nucleus magnocellularis (NM) and GABAergic inhibition from the ipsilateral superior olivary nucleus. Here, we study metabotropic glutamate receptor (mGluR)- and GABAB receptor (GABABR)-mediated modulation of synaptic transmission in NL neurons. Gramicidin-perforated recordings from acute brain stem slice preparations showed that the reversal potential of the GABAergic responses in NL neurons was more depolarized than the spike threshold.