Standardized Methodologies to Utilize Exosome Treatment as Potential Nano Substances in Hearing Loss

Recently, studies on the mechanism and clinical application of stem cell-derived exosomes have increased. Although the number of patients with hearing loss is increasing, there is no ideal therapy for the recovery of auditory cells of an independent organ in humans. In this review, we proposed the use of stem cell-derived exosomes for treating hearing loss and summarized the exosome research strategy platform for preclinical studies. It is necessary to select a research direction to assess direct or indirect effects on recipients based on the physiological mechanisms of exosomes that deliver useful molecules (called payloads) to recipient cells or tissues. To apply exosomes in the auditory field, researchers should select a model for assessing the toxicity to the auditory cells and analyzing their mechanisms in the recipient tissue. Such in vitro, ex vivo, and in vivo models have been designed and reported in previous studies. The analytical strategies in various models can evaluate the mechanism of exosomes based on exosome surface markers or the payload, thus helping the researchers in finding evidence regarding the efficacy of exosomes. Here, we propose three strategies for exosome application research in the auditory field.

Deafness Weakens Interareal Couplings in the Auditory Cortex

The function of the cerebral cortex essentially depends on the ability to form functional assemblies across different cortical areas serving different functions. Here we investigated how developmental hearing experience affects functional and effective interareal connectivity in the auditory cortex in an animal model with years-long and complete auditory deprivation (deafness) from birth, the congenitally deaf cat (CDC). Using intracortical multielectrode arrays, neuronal activity of adult hearing controls and CDCs was registered in the primary auditory cortex and the secondary posterior auditory field (PAF). Ongoing activity as well as responses to acoustic stimulation (in adult hearing controls) and electric stimulation applied via cochlear implants (in adult hearing controls and CDCs) were analyzed. As functional connectivity measures pairwise phase consistency and Granger causality were used. While the number of coupled sites was nearly identical between controls and CDCs, a reduced coupling strength between the primary and the higher order field was found in CDCs under auditory stimulation. Such stimulus-related decoupling was particularly pronounced in the alpha band and in top–down direction. Ongoing connectivity did not show such a decoupling. These findings suggest that developmental experience is essential for functional interareal interactions during sensory processing. The outcomes demonstrate that corticocortical couplings, particularly top-down connectivity, are compromised following congenital sensory deprivation.

Sparse Coding in Temporal Association Cortex Improves Complex Sound Discriminability

The mouse auditory cortex is comprised of several auditory fields spanning the dorso-ventral axis of the temporal lobe. The ventral most auditory field is the temporal association cortex (TeA), which remains largely unstudied. Using Neuropixels probes, we simultaneously recorded from primary auditory cortex (AUDp), secondary auditory cortex (AUDv) and TeA, characterizing neuronal responses to pure tones and frequency modulated (FM) sweeps in awake head-restrained mice. As compared to primary and secondary auditory cortices, single unit responses to pure tones in TeA were sparser, delayed and prolonged. Responses to FMs were also sparser. Population analysis showed that the sparser responses in TeA render it less sensitive to pure tones, yet more sensitive to FMs. When characterizing responses to pure tones under anesthesia, the distinct signature of TeA was changed considerably as compared to that in awake mice, implying that responses in TeA are strongly modulated by non-feedforward connections. Together with the known connectivity profile of TeA, these findings suggest that sparse representation of sounds in TeA supports selectivity to higher-order features of sounds and more complex auditory computations.

Microbial Sensing: Constructing Perception through Technological Layers

The author introduces the concept of looking without seeing to describe the layered use of technology required to experience microorganisms during the making of The Stars Beneath Our Feet: an audiovisual installation for Lumiere Durham, a four-day international light festival produced by Artichoke in the U.K. First, the author describes the experience of technological layering when attempting to perceive microorganisms in the visual field and then the methodology adopted to determine how the same microorganisms might be perceived in the auditory field. The conclusion describes the author's sense of being with the organism as a form of constructed perception in the context of “looking for” and “listening for” microorganisms through an expanded technological frame.

Phase-amplitude coupling profiles differ in frontal and auditory cortices

Neural oscillations are at the core of important computations in the mammalian brain. Interactions between oscillatory activities in different frequency bands, such as delta (1-4 Hz), theta (4-8 Hz), or gamma (>30 Hz), are a powerful mechanism for binding fundamentally distinct spatiotemporal scales of neural processing. Phase-amplitude coupling (PAC) is one such plausible and well-described interaction, but much is yet to be uncovered regarding how PAC dynamics contribute to sensory representations. In particular, although PAC appears to have a major role in audition, the characteristics of coupling profiles in sensory and integration (i.e. frontal) cortical areas remain obscure. Here, we address this question by studying PAC dynamics in the frontal-auditory field (FAF; an auditory area in the bat frontal cortex) and the auditory cortex (AC) of the bat Carollia perspicillata. By means of simultaneous electrophysiological recordings in frontal and auditory cortices examining local-field potentials (LFPs), we show that the amplitude of gamma-band activity couples with the phase of low-frequency LFPs in both structures. Our results demonstrate that the coupling in FAF occurs most prominently in delta/high-gamma frequencies (1-4/75-100 Hz), whereas in the AC the coupling is strongest in the theta/low-gamma (2-8/25-55 Hz) range. We argue that distinct PAC profiles may represent different mechanisms for neuronal processing in frontal and auditory cortices, and might complement oscillatory interactions for sensory processing in the frontal-auditory cortex network.

Reciprocal connectivity between secondary auditory cortical field and amygdala in mice

Recent studies have examined the feedback pathway from the amygdala to the auditory cortex in conjunction with the feedforward pathway from the auditory cortex to the amygdala. However, these connections have not been fully characterized. Here, to visualize the comprehensive connectivity between the auditory cortex and amygdala, we injected cholera toxin subunit b (CTB), a bidirectional tracer, into multiple subfields in the mouse auditory cortex after identifying the location of these subfields using flavoprotein fluorescence imaging. After injecting CTB into the secondary auditory field (A2), we found densely innervated CTB-positive axon terminals that were mainly located in the lateral amygdala (La), and slight innervations in other divisions such as the basal amygdala. Moreover, we found a large number of retrogradely-stained CTB-positive neurons in La after injecting CTB into A2. When injecting CTB into the primary auditory cortex (A1), a small number of CTB-positive neurons and axons were visualized in the amygdala. Finally, we found a near complete absence of connections between the other auditory cortical fields and the amygdala. These data suggest that reciprocal connections between A2 and La are main conduits for communication between the auditory cortex and amygdala in mice.