Development in the Mammalian Auditory System Depends on Transcription Factors

We review the molecular basis of several transcription factors (Eya1, Sox2), including the three related genes coding basic helix–loop–helix (bHLH; see abbreviations) proteins (Neurog1, Neurod1, Atoh1) during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires Neurog1, followed by its downstream target Neurod1, to cross-regulate Atoh1 expression. In contrast, hair cells and cochlear nuclei critically depend on Atoh1 and require Neurod1 expression for interactions with Atoh1. Upregulation of Atoh1 following Neurod1 loss changes some vestibular neurons’ fate into “hair cells”, highlighting the significant interplay between the bHLH genes. Further work showed that replacing Atoh1 by Neurog1 rescues some hair cells from complete absence observed in Atoh1 null mutants, suggesting that bHLH genes can partially replace one another. The inhibition of Atoh1 by Neurod1 is essential for proper neuronal cell fate, and in the absence of Neurod1, Atoh1 is upregulated, resulting in the formation of “intraganglionic” HCs. Additional genes, such as Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b, play a role in the auditory system. Finally, both Lmx1a and Lmx1b genes are essential for the cochlear organ of Corti, spiral ganglion neuron, and cochlear nuclei formation. We integrate the mammalian auditory system development to provide comprehensive insights beyond the limited perception driven by singular investigations of cochlear neurons, cochlear hair cells, and cochlear nuclei. A detailed analysis of gene expression is needed to understand better how upstream regulators facilitate gene interactions and mammalian auditory system development.

Imaging of Auditory Brain Stem Implants

Auditory brain stem implants are infrequently encountered neuroprosthetic devices used for auditory rehabilitation in deaf patients with pathology between the cochlea and cochlear nuclei who would not benefit from cochlear implantation. This article reviews the device, the relevant anatomy, audiologic performance, operative approaches, and conditions in which auditory brain stem implants are indicated. The imaging appearance of auditory brain stem implants, including optimal lead positioning, and imaging safety considerations of the device are also discussed. Knowledge of the device can assist the radiologist in detecting postoperative complications and component malpositioning and in providing safe and effective imaging practices in patients with indwelling auditory brain stem implants.Learning Objective: To describe the auditory brain stem implant device, identify optimal lead positioning, and list indications for auditory brain stem implant placement.

Auditory brainstem models: adapting cochlear nuclei improve spatial encoding by the medial superior olive in reverberation

Listeners perceive sound-energy as originating from the direction of its source, even as direct sound is followed milliseconds later by reflected sound from multiple different directions. Early-arriving sound is emphasised in the ascending auditory pathway, including the medial superior olive (MSO) where binaural neurons encode the interaural time difference (ITD) cue for spatial location. Behaviourally, weighting of ITD conveyed during rising sound-energy is stronger at 600 Hz, a frequency with higher reverberant energy, than at 200 Hz where reverberant energy is lower. Here we computationally explore the combined effectiveness of adaptation before ITD-encoding, and excitatory binaural coincidence detection within MSO neurons, in emphasising ITD conveyed in early-arriving sound. With excitatory inputs from adapting model spherical bushy cells (SBCs) of the bilateral cochlear nuclei, a Hodgkin-Huxley-type model MSO neuron reproduces the frequency-dependent emphasis of rising vs. peak sound-energy in ITD-encoding. Maintaining the adaptation in model SBCs, and adjusting membrane speed in model MSO neurons, hemispheric populations of model SBCs and MSO neurons, with simplified membranes for computational efficiency, also reproduce the stronger weighting of ITD information conveyed during rising sound-energy at 600 Hz compared to 200 Hz. This hemispheric model further demonstrates a link between strong weighting of spatial information during rising sound-energy, and correct unambiguous lateralisation of reverberant speech.

Presynaptic GABAergic receptors modulate inhibitory synaptic feedback in the avian cochlear nucleus angularis

Inhibition plays multiple critical roles in the neural processing of sound. In the avian auditory brain stem, the cochlear nuclei receive their principal inhibitory feedback from the superior olivary nucleus (SON) in lieu of local inhibitory circuitry. In the timing pathway, GABAergic inhibitory feedback underlies gain control to enhance sound localization. In the cochlear nucleus angularis (NA), which processes intensity information, how the inhibitory feedback is integrated is not well understood. Using whole cell patch-clamp recordings in chick brain stem slices, we investigated the effects of GABA release on the inhibitory (presumed SON) and excitatory (8th nerve) synaptic inputs onto NA neurons. Pharmacological activation of the metabotropic GABAB receptors with baclofen profoundly suppressed both evoked excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). Baclofen similarly reduced the frequency of spontaneous IPSCs and EPSCs, but had no significant effect on the current kinetics or amplitudes, indicating a presynaptic locus of modulation. Trains of IPSCs showed substantial transient and sustained short-term synaptic facilitation. Baclofen application reduced the initial IPSC amplitude, but enhanced the relative facilitation over the train via changes in release probability. Comparable levels of GABAB receptor mediated blockade also shifted short-term synaptic plasticity of EPSCs toward less depression. Evoked (but not spontaneous) release of GABA was sufficient to suppress basal release at inhibitory synapses in slices. Overall, the modulation of excitatory and inhibitory inputs of NA neurons via GABAB receptor activation appears to parallel that in the timing pathway.New and NoteworthyAvian cochlear nucleus angularis (NA) neurons are responsible for encoding sound intensity and provide level information for gain control feedback via the superior olivary nucleus. This GABAergic inhibitory feedback was itself modulated in NA via presynaptic, metabotropic GABAB receptor mediated suppression. Excitatory transmission was modulated by the same receptors, suggesting parallel homosynaptic and heterosynaptic mechanisms in both cochlear nuclei.

The Cochlear Nuclei

Plasticity in neuronal circuits is essential for optimizing connections as animals develop and for adapting to injuries and aging, but it can also distort the processing, as well as compromise the conveyance of ongoing sensory information. This chapter summarizes evidence from electrophysiological studies in slices and in vivo that shows how remarkably robust signaling is in principal cells of the ventral cochlear nucleus. Even in the face of short-term plasticity, these neurons signal rapidly and with temporal precision. They can relay ongoing acoustic information from the cochlea to the brain largely independently of sounds to which they were exposed previously.