Tinnitus mechanisms and the need for an objective electrophysiological tinnitus test.

Tinnitus, the perception of sound with no external auditory stimulus, is a complex, multifaceted, and potentially devastating disorder. Despite recent advances in our understanding of tinnitus, there are limited options for effective treatment. Tinnitus treatments are made more complicated by the lack of a test for tinnitus based on objectively measured physiological characteristics.

Comparison of two behavioral tests for tinnitus assessment in mice.

Animal research focused on chronic tinnitus associated with noise-induced hearing loss can be expensive and time-consuming as a result of the behavioral training required. Although there exist a number of behavioral tests for tinnitus; there have been few formal direct comparisons of these tests. Here, we evaluated animals in two different tinnitus assessment methods.

Long-Duration Sound-Induced Facilitation Changes Population Activity in the Inferior Colliculus.

The inferior colliculus (IC) is at the midpoint of the auditory system and integrates virtually all information ascending from the auditory brainstem, organizes it, and transmits the results to the auditory forebrain. Its abundant, excitatory local connections are crucial for this task. This study describes a long duration sound (LDS)-induced potentiation in the IC that changes both subsequent tone-evoked responses and spontaneous activity.

C1ql1 is expressed in adult outer hair cells of the cochlea in a tonotopic gradient.

Hearing depends on the transduction of sounds into neural signals by the inner hair cells of the cochlea. Cochleae also have outer hair cells with unique electromotile properties that increase auditory sensitivity, but they are particularly susceptible to damage by intense noise exposure, ototoxic drugs, and aging. Although the outer hair cells have synapses on afferent neurons that project to the brain, the function of this neuronal circuit is unclear.

Neuronal sensitivity to the interaural time difference of the sound envelope in the mouse inferior colliculus.

We examined the sensitivity of the neurons in the mouse inferior colliculus (IC) to the interaural time differences (ITD) conveyed in the sound envelope. Utilizing optogenetic methods, we compared the responses to the ITD in the envelope of identified glutamatergic and GABAergic neurons. More than half of both cell types were sensitive to the envelope ITD, and the ITD curves were aligned at their troughs.

Mice heterozygous for the Cdh23/Ahl1 mutation show age-related deficits in auditory temporal processing.

A mutation in the Cdh23 gene is implicated in both syndromic and nonsyndromic hearing loss in humans and age-related hearing loss in C57BL/6 mice. It is generally assumed that human patients (as well as mouse models) only have a hearing loss phenotype if the mutation is homozygous. However, a major complaint for patients with a hearing disability is a reduced speech intelligibility that may be related to temporal processing deficits rather than just elevated thresholds.

Intravenously-injected gold nanoparticles (AuNPs) access intracerebral F98 rat gliomas better than AuNPs infused directly into the tumor site by convection enhanced delivery.

Background: Intravenously (IV)-injected gold nanoparticles (AuNPs) powerfully enhance the efficacy of X-ray therapy of tumors including advanced gliomas. However, pharmacokinetic issues, such as slow tissue clearance and skin discoloration, may impede clinical translation. The direct infusion of AuNPs into the tumor might be an alternative mode of delivery.

Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain.

Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice.

Functional organization of the local circuit in the inferior colliculus.

The inferior colliculus (IC) is the first integration center of the auditory system. After the transformation of sound to neural signals in the cochlea, the signals are analyzed by brainstem auditory nuclei that, in turn, transmit this information to the IC. However, the neural circuitry that underlies this integration is unclear.

Differences in the strength of cortical and brainstem inputs to SSA and non-SSA neurons in the inferior colliculus.

In an ever changing auditory scene, change detection is an ongoing task performed by the auditory brain. Neurons in the midbrain and auditory cortex that exhibit stimulus-specific adaptation (SSA) may contribute to this process. Those neurons adapt to frequent sounds while retaining their excitability to rare sounds.

Differential distribution of GABA and glycine terminals in the inferior colliculus of rat and mouse.

The inferior colliculus (IC), the midbrain component of the auditory pathway, integrates virtually all inputs from the auditory brainstem. These are a mixture of excitatory and inhibitory ascending inputs, and the inhibitory transmitters include both gamma-aminobutyric acid (GABA) and glycine (GLY). Although the presence of these inhibitory inputs is well established, their relative location in the IC is not, and there is little information on the mouse.

Convergence of Lemniscal and Local Excitatory Inputs on Large GABAergic Tectothalamic Neurons.

Large GABAergic (LG) neurons form a distinct cell type in the inferior colliculus (IC), identified by the presence of dense VGLUT2-containing axosomatic terminals. Although some of the axosomatic terminals originate from local and commissural IC neurons, it has been unclear whether LG neurons also receive axosomatic inputs from the lower auditory brainstem nuclei, i.e.

Asymmetric temporal interactions of sound-evoked excitatory and inhibitory inputs in the mouse auditory midbrain.

In the auditory midbrain, synaptic mechanisms responsible for the precise temporal coding of inputs in the brainstem are absent. Instead, in the inferior colliculus (IC), the diverse temporal firing patterns must be coded by other synaptic mechanisms, about which little is known. Here, we demonstrate the temporal characteristics of sound-evoked excitatory and inhibitory postsynaptic currents (seEPSCs and seIPSCs, respectively) in vivo in response to long-duration tones.

Local and commissural IC neurons make axosomatic inputs on large GABAergic tectothalamic neurons.

Large GABAergic (LG) neurons are a distinct type of neuron in the inferior colliculus (IC) identified by their dense vesicular glutamate transporter 2 (VGLUT2)-containing axosomatic synaptic terminals. Yet the sources of these terminals are unknown. Since IC glutamatergic neurons express VGLUT2, and IC neurons are known to have local collaterals, we tested the hypothesis that these excitatory, glutamatergic axosomatic inputs on LG neurons come from local axonal collaterals and commissural IC neurons.

The balance of excitatory and inhibitory synaptic inputs for coding sound location.

The localization of high-frequency sounds in the horizontal plane uses an interaural-level difference (ILD) cue, yet little is known about the synaptic mechanisms that underlie processing this cue in the inferior colliculus (IC) of mouse. Here, we study the synaptic currents that process ILD in vivo and use stimuli in which ILD varies around a constant average binaural level (ABL) to approximate sounds on the horizontal plane. Monaural stimulation in either ear produced EPSCs and IPSCs in most neurons.

Gene expression identifies distinct ascending glutamatergic pathways to frequency-organized auditory cortex in the rat brain.

A conserved feature of sound processing across species is the presence of multiple auditory cortical fields with topographically organized responses to sound frequency. Current organizational schemes propose that the ventral division of the medial geniculate body (MGBv) is a single functionally homogenous structure that provides the primary source of input to all neighboring frequency-organized cortical fields. These schemes fail to account for the contribution of MGBv to functional diversity between frequency-organized cortical fields.

The basic circuit of the IC: tectothalamic neurons with different patterns of synaptic organization send different messages to the thalamus.

The inferior colliculus (IC) in the midbrain of the auditory system uses a unique basic circuit to organize the inputs from virtually all of the lower auditory brainstem and transmit this information to the medial geniculate body (MGB) in the thalamus. Here, we review the basic circuit of the IC, the neuronal types, the organization of their inputs and outputs. We specifically discuss the large GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the more numerous glutamatergic neurons.

Expression of glutamate and inhibitory amino acid vesicular transporters in the rodent auditory brainstem.

Glutamate is the main excitatory neurotransmitter in the auditory system, but associations between glutamatergic neuronal populations and the distribution of their synaptic terminations have been difficult. Different subsets of glutamatergic terminals employ one of three vesicular glutamate transporters (VGLUT) to load synaptic vesicles. Recently, VGLUT1 and VGLUT2 terminals were found to have different patterns of organization in the inferior colliculus, suggesting that there are different types of glutamatergic neurons in the brainstem auditory system with projections to the colliculus.

Origins of Glutamatergic Terminals in the Inferior Colliculus Identified by Retrograde Transport and Expression of VGLUT1 and VGLUT2 Genes.

Terminals containing vesicular glutamate transporter (VGLUT) 2 make dense axosomatic synapses on tectothalamic GABAergic neurons. These are one of the three types of glutamatergic synapses in the inferior colliculus (IC) identified by one of three combinations of transporter protein: VGLUT1 only, VGLUT2 only, or both VGLUT1 and 2. To identify the source(s) of these three classes of glutamatergic terminals, we employed the injection of Fluorogold (FG) into the IC and retrograde transport in combination with in situ hybridization for VGLUT1 and VGLUT2 mRNA.

Differential patterns of inputs create functional zones in central nucleus of inferior colliculus.

Distinct pathways carry monaural and binaural information from the lower auditory brainstem to the central nucleus of the inferior colliculus (ICC). Previous anatomical and physiological studies suggest that differential ascending inputs to regions of the ICC create functionally distinct zones. Here, we provide direct evidence of this relationship by combining recordings of single unit responses to sound in the ICC with focal, iontophoretic injections of the retrograde tracer Fluoro-Gold at the physiologically characterized sites.

Regulation of Kv channel expression and neuronal excitability in rat medial nucleus of the trapezoid body maintained in organotypic culture.

Principal neurons of the medial nucleus of the trapezoid body (MNTB) express a spectrum of voltage-dependent K(+) conductances mediated by Kv1-Kv4 channels, which shape action potential (AP) firing and regulate intrinsic excitability. Postsynaptic factors influencing expression of Kv channels were explored using organotypic cultures of brainstem prepared from P9-P12 rats and maintained in either low (5 mm, low-K) or high (25 mm, high-K) [K(+)](o) medium. Whole cell patch-clamp recordings were made after 7-28 days in vitro.

Two classes of GABAergic neurons in the inferior colliculus.

The inferior colliculus (IC) is unique, having both glutamatergic and GABAergic projections ascending to the thalamus. Although subpopulations of GABAergic neurons in the IC have been proposed, criteria to distinguish them have been elusive and specific types have not been associated with specific neural circuits. Recently, the largest IC neurons were found to be recipients of somatic terminals containing vesicular glutamate transporter 2 (VGLUT2).