Temporary Unilateral Hearing Loss Impairs Spatial Auditory Information Processing in Neurons in the Central Auditory System

Temporary conductive hearing loss (CHL) can lead to hearing impairments that persist beyond resolution of the CHL. In particular, unilateral CHL leads to deficits in auditory skills that rely on binaural input (e.g., spatial hearing). Here, we asked whether single neurons in the auditory midbrain, which integrate acoustic inputs from the two ears, are altered by a temporary CHL. We introduced 6 weeks of unilateral CHL to young adult chinchillas via foam earplug. Following CHL removal and restoration of peripheral input, single-unit recordings from inferior colliculus (ICC) neurons revealed the CHL decreased the efficacy of inhibitory input to the ICC contralateral to the earplug and increased inhibitory input ipsilateral to the earplug, effectively creating a higher proportion of monaural responsive neurons than binaural. Moreover, this resulted in a ∼10 dB shift in the coding of a binaural sound location cue (interaural-level difference, ILD) in ICC neurons relative to controls. The direction of the shift was consistent with a compensation of the altered ILDs due to the CHL. ICC neuron responses carried ∼37% less information about ILDs after CHL than control neurons. Cochlear peripheral-evoked responses confirmed that the CHL did not induce damage to the auditory periphery. We find that a temporary CHL altered auditory midbrain neurons by shifting binaural responses to ILD acoustic cues, suggesting a compensatory form of plasticity occurring by at least the level of the auditory midbrain, the ICC.

Population registration of echo flow in the big brown bat’s auditory midbrain

Echolocating bats navigate through cluttered environments that return cascades of echoes in response to the bat’s broadcasts. We show that local field potentials from the big brown bat’s auditory midbrain have consistent responses to a simulated echo cascade varying across echo delays and stimulus amplitudes, despite different underlying individual neuronal selectivities. These results suggest that population activity in the midbrain can build a cohesive percept of an auditory scene by aggregating activity over neuronal subpopulations.

5-HT1A Receptors Alter Temporal Responses to Broadband Vocalizations in the Mouse Inferior Colliculus Through Response Suppression

Neuromodulatory systems may provide information on social context to auditory brain regions, but relatively few studies have assessed the effects of neuromodulation on auditory responses to acoustic social signals. To address this issue, we measured the influence of the serotonergic system on the responses of neurons in a mouse auditory midbrain nucleus, the inferior colliculus (IC), to vocal signals. Broadband vocalizations (BBVs) are human-audible signals produced by mice in distress as well as by female mice in opposite-sex interactions. The production of BBVs is context-dependent in that they are produced both at early stages of interactions as females physically reject males and at later stages as males mount females. Serotonin in the IC of males corresponds to these events, and is elevated more in males that experience less female rejection. We measured the responses of single IC neurons to five recorded examples of BBVs in anesthetized mice. We then locally activated the 5-HT1A receptor through iontophoretic application of 8-OH-DPAT. IC neurons showed little selectivity for different BBVs, but spike trains were characterized by local regions of high spike probability, which we called “response features.” Response features varied across neurons and also across calls for individual neurons, ranging from 1 to 7 response features for responses of single neurons to single calls. 8-OH-DPAT suppressed spikes and also reduced the numbers of response features. The weakest response features were the most likely to disappear, suggestive of an “iceberg”-like effect in which activation of the 5-HT1A receptor suppressed weakly suprathreshold response features below the spiking threshold. Because serotonin in the IC is more likely to be elevated for mounting-associated BBVs than for rejection-associated BBVs, these effects of the 5-HT1A receptor could contribute to the differential auditory processing of BBVs in different behavioral subcontexts.

Inverse Density of Iba1 and Glutamine Synthetase Expressing Glia in Rat Inferior Colliculus

Microglia and astrocytes undertake numerous essential roles in nervous systems but we know little of their anatomical distribution within numerous nuclei. In the principal nuclei of the mammalian auditory midbrain, the inferior colliculi (IC), the cellular density and relative distribution of glutamate synthetase (GS) expressing astrocytes and ionized calcium-binding adapter molecule 1 (Iba1) expressing microglia is unknown. To address this, the IC of young adult, male Wistar rats were immunohistochemically labelled for GS and Iba1, using chromogenic methods. Sub-regions of imaged IC sections were demarked and soma density of both cell types determined. GS labelled somata were twice more densely packed as Iba1 labelled somata throughout IC parenchyma and peri-vascular regions. Furthermore, GS labelled somata density was significantly lower in dorsal cortex than external cortex or central nucleus. Iba1 labelled somata density exhibited the opposite trend, revealing an inverse density of these glial cell types between IC sub-regions. GS labelled neuropil was strongest in the cortices with and a gradual transition of lighter labelling towards central nucleus. These data provide the first detailed descriptions of GS labelling in IC and demonstrate sub-regional differences in IC glial cell density. Taken together, these findings suggest neurochemical specialization of glia in IC sub-regions, likely related to local physiological and metabolic demands, with implications for IC function.

Subcortical circuits mediate communication between primary sensory cortical areas in mice

Integration of information across the senses is critical for perception and is a common property of neurons in the cerebral cortex, where it is thought to arise primarily from corticocortical connections. Much less is known about the role of subcortical circuits in shaping the multisensory properties of cortical neurons. We show that stimulation of the whiskers causes widespread suppression of sound-evoked activity in mouse primary auditory cortex (A1). This suppression depends on the primary somatosensory cortex (S1), and is implemented through a descending circuit that links S1, via the auditory midbrain, with thalamic neurons that project to A1. Furthermore, a direct pathway from S1 has a facilitatory effect on auditory responses in higher-order thalamic nuclei that project to other brain areas. Crossmodal corticofugal projections to the auditory midbrain and thalamus therefore play a pivotal role in integrating multisensory signals and in enabling communication between different sensory cortical areas.

Constant Resting Frequency and Auditory Midbrain Neuronal Frequency Analysis of Hipposideros pratti in Background White Noise

Acoustic communication signals are inevitably challenged by ambient noise. In response to noise, many animals adjust their calls to maintain signal detectability. However, the mechanisms by which the auditory system adapts to the adjusted pulses are unclear. Our previous study revealed that the echolocating bat, Hipposideros pratti, increased its pulse intensity in the presence of background white noise. In vivo single-neuron recording demonstrated that the auditory midbrain neurons tuned to the second harmonic (H2 neurons) increased their minimal threshold (MT) to a similar degree as the increment of pulse intensity in the presence of the background noise. Furthermore, the H2 neurons exhibited consistent spike rates at their best amplitudes and sharper intensity tuning with background white noise compared with silent conditions. The previous data indicated that sound intensity analysis by auditory midbrain neurons was adapted to the increased pulse intensity in the same noise condition. This study further examined the echolocation pulse frequency and frequency analysis of auditory midbrain neurons with noise conditions. The data revealed that H. pratti did not shift the resting frequency in the presence of background noise. The auditory midbrain neuronal frequency analysis highly linked to processing the resting frequency with the presence of noise by presenting the constant best frequency (BF), frequency sensitivity, and frequency selectivity. Thus, our results suggested that auditory midbrain neuronal responses in background white noise are adapted to process echolocation pulses in the noise conditions.

Nitric oxide signalling underlies salicylate-induced increases in neuronal firing in the inferior colliculus: a central mechanism of tinnitus?

The tinnitus-inducing agent salicylate reduces cochlear output but causes hyperactivity in higher auditory centres, including the inferior colliculus (the auditory midbrain). Using multi-electrode recording in anaesthetised guinea pigs (Cavia porcellus), we addressed the hypothesis that salicylate-induced hyperactivity in the inferior colliculus involves nitric oxide signalling secondary to increased ascending excitatory input. In the inferior colliculus, systemic salicylate (200 mg/kg i.p., 0 h) markedly increased spontaneous and sound-driven neuronal firing (3-6 h post drug) with both onset and sustained responses to pure tones being massively increased. Reverse microdialysis of increasing concentrations of salicylate directly into the inferior colliculus (100 μM-10 mM, from 0 h) failed to mimic systemic salicylate. In contrast, it caused a small, transient, increase in sound-driven firing (1 h), followed by a larger sustained decrease in both spontaneous and sound-driven firing (2-5 h). When salicylate was given systemically, reverse microdialysis of the neuronal nitric oxide synthase inhibitor L-methyl arginine into the inferior colliculus (500 mM, 2-6 h) completely blocked the salicylate-induced increase in spontaneous and sound-driven neuronal firing. Our data indicate that systemic salicylate induces neuronal hyperactivity in the auditory midbrain via a mechanism outside the inferior colliculus, presumably upstream in the auditory pathway; and that the mechanism is ultimately dependent on nitric oxide signalling within the inferior colliculus. Given that nitric oxide is known to mediate NMDA receptor signalling in the inferior colliculus, we propose that salicylate activates an ascending glutamatergic input to the inferior colliculus and that this is an important mechanism underlying salicylate-induced tinnitus.

Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus

The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.