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Hearing Research Aug 2024Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of...
Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of perceptual objects from sensory features. Oscillatory activity can be differentiated into stimulus-phase-locked (evoked) and non-phase-locked (induced). The former is mainly determined by sensory input, the latter by higher-level (cortical) processing. Effects of auditory deprivation on cortical oscillations have been studied in congenitally deaf cats (CDCs) using cochlear implant (CI) stimulation. CI-induced alpha, beta, and gamma activity were compromised in the auditory cortex of CDCs. Furthermore, top-down information flow between secondary and primary auditory areas in hearing cats, conveyed by induced alpha oscillations, was lost in CDCs. Here we used the matching pursuit algorithm to assess components of such oscillatory activity in local field potentials recorded in primary field A1. Additionally to the loss of induced alpha oscillations, we also found a loss of evoked theta activity in CDCs. The loss of theta and alpha activity in CDCs can be directly related to reduced high-frequency (gamma-band) activity due to cross-frequency coupling. Here we quantified such cross-frequency coupling in adult 1) hearing-experienced, acoustically stimulated cats (aHCs), 2) hearing-experienced cats following acute pharmacological deafening and subsequent CIs, thus in electrically stimulated cats (eHCs), and 3) electrically stimulated CDCs. We found significant cross-frequency coupling in all animal groups in > 70% of auditory-responsive sites. The predominant coupling in aHCs and eHCs was between theta/alpha phase and gamma power. In CDCs such coupling was lost and replaced by alpha oscillations coupling to delta/theta phase. Thus, alpha/theta oscillations synchronize high-frequency gamma activity only in hearing-experienced cats. The absence of induced alpha and theta oscillations contributes to the loss of induced gamma power in CDCs, thereby signifying impaired local network activity.
Topics: Animals; Cats; Auditory Cortex; Deafness; Acoustic Stimulation; Gamma Rhythm; Cochlear Implants; Alpha Rhythm; Evoked Potentials, Auditory; Algorithms; Auditory Pathways; Disease Models, Animal; Theta Rhythm
PubMed: 38797035
DOI: 10.1016/j.heares.2024.109032 -
Bioengineering (Basel, Switzerland) Apr 2024Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available.... (Review)
Review
Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear's architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions.
PubMed: 38790292
DOI: 10.3390/bioengineering11050425 -
BioRxiv : the Preprint Server For... May 2024The posterior "tail" region of the striatum receives dense innervation from sensory brain regions and has been demonstrated to play a role in behaviors that require...
The posterior "tail" region of the striatum receives dense innervation from sensory brain regions and has been demonstrated to play a role in behaviors that require sensorimotor integration including discrimination , avoidance and defense responses. The output neurons of the striatum, the D1 and D2 striatal projection neurons (SPNs) that make up the direct and indirect pathways, respectively, are thought to play differential roles in these behavioral responses, although it remains unclear if or how these neurons display differential responsivity to sensory stimuli. Here, we used whole-cell recordings in vivo and ex vivo to examine the strength of excitatory and inhibitory synaptic inputs onto D1 and D2 SPNs following the stimulation of upstream auditory pathways. While D1 and D2 SPNs both displayed stimulus-evoked depolarizations, D1 SPN responses were stronger and faster for all stimuli tested in vivo as well as in brain slices. This difference did not arise from differences in the strength of excitatory inputs but from differences in the strength of feed forward inhibition. Indeed, fast spiking interneurons, which are readily engaged by auditory afferents exerted stronger inhibition onto D2 SPNs compared to D1 SPNs. Our results support a model in which differences in feed forward inhibition enable the preferential recruitment of the direct pathway in response to auditory stimuli, positioning this pathway to initiate sound-driven actions.
PubMed: 38766066
DOI: 10.1101/2024.05.09.592848 -
Epilepsy & Behavior : E&B Jul 2024In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a... (Review)
Review
In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a number of limbic and thalamo-cortical related structures involved in the processing of musical emotion (exposure), including the amygdala (arousal, expression of mood, fear), hippocampus (memory, regulation of HPA axis, stress), parahippocampal gyrus (recognition, memory retrieval), insula (valence), temporal poles (connectivity), ventral striatum (expectation and experience of reward), orbitofrontal cortex (valence) and cingulate cortex (autonomic regulation). One method is to audify (a form of sonification) EEG activity to find music by feedback to entrain abnormal EEG activity. We discuss various methods and our use of X-System (https://www.x-system.co.uk/) which is a computational model of the musical brain capable of predicting the neurophysiological effects of music. It models structures and pathways related to responses to music, including the cochlea, brain stem, auditory and motor cortex, as well as basal ganglia, cerebellum and limbic structures. It can predict autonomic and endocrine activity as well as the substrates of electrical activity to select music which can regularise EEG abnormalities to decrease epileptic activity and seizures, especially in those unresponsive to antiepileptic medication or invasive treatments.
Topics: Humans; Epilepsy; Music Therapy; Music; Electroencephalography; Brain; Auditory Perception; Precision Medicine
PubMed: 38761451
DOI: 10.1016/j.yebeh.2024.109829 -
The Journal of the Acoustical Society... May 2024Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise....
Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.
Topics: Animals; Female; Male; Mice; Acoustic Stimulation; Auditory Pathways; Auditory Perception; Auditory Threshold; Behavior, Animal; Cochlea; Evoked Potentials, Auditory, Brain Stem; Hearing; Mice, Inbred C57BL; Mice, Knockout; Noise; Olivary Nucleus; Perceptual Masking; Phenotype; Receptors, Nicotinic; Reflex, Startle
PubMed: 38738939
DOI: 10.1121/10.0025985 -
Cureus Apr 2024Bickerstaff brainstem encephalitis (BBE) is a rare disorder that is characterized by ophthalmoplegia, ataxia, and disturbance in consciousness. Definite diagnosis is...
Bickerstaff brainstem encephalitis (BBE) is a rare disorder that is characterized by ophthalmoplegia, ataxia, and disturbance in consciousness. Definite diagnosis is made primarily through clinical presentation and serology testing with anti-GQ1b antibody. However, in a country where access to serologic testing is scarce, electrophysiologic tests such as brainstem auditory evoked response (BAER) may contribute to the diagnosis. Due to its rarity and generally good prognosis, there is no established consensus for the treatment of BBE. Immunomodulatory treatments such as intravenous immunoglobulin (IVIG), plasma exchange, steroids, or a combination of these therapies are often used with good response. However, there are severe cases that respond poorly to these conventional treatments. We report the case of a 26-year-old Filipino man who came in for sudden onset of diplopia, with a one-week history of upper respiratory tract infection. Subsequently, he developed paresthesias, quadriparesis, and an altered level of consciousness. On initial examination, he only had partial third nerve palsy, but eventually became quadriparetic and obtunded during admission. Initial electromyography and nerve conduction velocity (EMG-NCV) study showed a reduced recruitment pattern of the right rectus femoris, absent H reflexes of bilateral posterior tibial nerves, and no abnormal increase in temporal dispersion. Cranial MRI with contrast was unremarkable. Video electroencephalogram (video-EEG) showed intermittent generalized 5-6 Hz and 6-7 Hz theta slowing of the background activity in the stimulated state. BAER was done revealing bilateral partial dysfunction of the auditory pathways to support brainstem involvement of the disease. He received IVIG and methylprednisolone pulse therapy with no significant clinical improvement. Hence, he was given a rituximab infusion. One week post-rituximab, he had sustained wakefulness and was able to move his extremities.
PubMed: 38738130
DOI: 10.7759/cureus.57993 -
Frontiers in Neural Circuits 2024The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The... (Comparative Study)
Comparative Study
The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.
Topics: Animals; Rats; Mice; Male; Neural Pathways; Intralaminar Thalamic Nuclei; Mice, Inbred C57BL; Rats, Sprague-Dawley; Female
PubMed: 38736977
DOI: 10.3389/fncir.2024.1384621 -
Hearing Research Jun 2024Cortical acetylcholine (ACh) release has been linked to various cognitive functions, including perceptual learning. We have previously shown that cortical cholinergic...
Cortical acetylcholine (ACh) release has been linked to various cognitive functions, including perceptual learning. We have previously shown that cortical cholinergic innervation is necessary for accurate sound localization in ferrets, as well as for their ability to adapt with training to altered spatial cues. To explore whether these behavioral deficits are associated with changes in the response properties of cortical neurons, we recorded neural activity in the primary auditory cortex (A1) of anesthetized ferrets in which cholinergic inputs had been reduced by making bilateral injections of the immunotoxin ME20.4-SAP in the nucleus basalis (NB) prior to training the animals. The pattern of spontaneous activity of A1 units recorded in the ferrets with cholinergic lesions (NB ACh) was similar to that in controls, although the proportion of burst-type units was significantly lower. Depletion of ACh also resulted in more synchronous activity in A1. No changes in thresholds, frequency tuning or in the distribution of characteristic frequencies were found in these animals. When tested with normal acoustic inputs, the spatial sensitivity of A1 neurons in the NB ACh ferrets and the distribution of their preferred interaural level differences also closely resembled those found in control animals, indicating that these properties had not been altered by sound localization training with one ear occluded. Simulating the animals' previous experience with a virtual earplug in one ear reduced the contralateral preference of A1 units in both groups, but caused azimuth sensitivity to change in slightly different ways, which may reflect the modest adaptation observed in the NB ACh group. These results show that while ACh is required for behavioral adaptation to altered spatial cues, it is not required for maintenance of the spectral and spatial response properties of A1 neurons.
Topics: Animals; Ferrets; Auditory Cortex; Acoustic Stimulation; Basal Forebrain; Sound Localization; Acetylcholine; Male; Cholinergic Neurons; Auditory Pathways; Female; Immunotoxins; Basal Nucleus of Meynert; Neurons; Auditory Threshold; Adaptation, Physiological; Behavior, Animal
PubMed: 38733712
DOI: 10.1016/j.heares.2024.109025 -
Cells Apr 2024In mammals, hearing loss is irreversible due to the lack of the regenerative capacity of the auditory epithelium. However, stem/progenitor cells in mammalian cochleae...
In mammals, hearing loss is irreversible due to the lack of the regenerative capacity of the auditory epithelium. However, stem/progenitor cells in mammalian cochleae may be a therapeutic target for hearing regeneration. The ubiquitin proteasome system plays an important role in cochlear development and maintenance. In this study, we investigated the role of ubiquitin C-terminal hydrolase L1 (UCHL1) in the process of the transdifferentiation of auditory supporting cells (SCs) into hair cells (HCs). The expression of UCHL1 gradually decreased as HCs developed and was restricted to inner pillar cells and third-row Deiters' cells between P2 and P7, suggesting that UCHL1-expressing cells are similar to the cells with Lgr5-positive progenitors. UCHL1 expression was decreased even under conditions in which supernumerary HCs were generated with a γ-secretase inhibitor and Wnt agonist. Moreover, the inhibition of UCHL1 by LDN-57444 led to an increase in HC numbers. Mechanistically, LDN-57444 increased mTOR complex 1 activity and allowed SCs to transdifferentiate into HCs. The suppression of UCHL1 induces the transdifferentiation of auditory SCs and progenitors into HCs by regulating the mTOR pathway.
Topics: Animals; Cell Transdifferentiation; Hair Cells, Auditory; Indoles; Labyrinth Supporting Cells; Oximes; Signal Transduction; TOR Serine-Threonine Kinases; Ubiquitin Thiolesterase; Rats
PubMed: 38727276
DOI: 10.3390/cells13090737 -
Aging Cell May 2024The voltage-gated Kv3.1/KCNC1 channel is abundantly expressed in fast-spiking principal neurons and GABAergic inhibitory interneurons throughout the ascending auditory...
The voltage-gated Kv3.1/KCNC1 channel is abundantly expressed in fast-spiking principal neurons and GABAergic inhibitory interneurons throughout the ascending auditory pathway and in various brain regions. Inactivating mutations in the KCNC1 gene lead to forms of epilepsy and a decline in the expression of the Kv3.1 channel is involved in age-related hearing loss. As oxidative stress plays a fundamental role in the pathogenesis of epilepsy and age-related hearing loss, we hypothesized that an oxidative insult might affect the function of this channel. To verify this hypothesis, the activity and expression of endogenous and ectopic Kv3.1 were measured in models of oxidative stress-related aging represented by cell lines exposed to 100 mM d-galactose. In these models, intracellular reactive oxygen species, thiobarbituric acid reactive substances, sulfhydryl groups of cellular proteins, and the activity of catalase and superoxide dismutase were dysregulated, while the current density of Kv3.1 was significantly reduced. Importantly, the antioxidant melatonin reverted all these effects. The reduction of function of Kv3.1 was not determined by direct oxidation of amino acid side chains of the protein channel or reduction of transcript or total protein levels but was linked to reduced trafficking to the cell surface associated with Src phosphorylation as well as metabolic and endoplasmic reticulum stress. The data presented here specify Kv3.1 as a novel target of oxidative stress and suggest that Kv3.1 dysfunction might contribute to age-related hearing loss and increased prevalence of epilepsy during aging. The pharmacological use of the antioxidant melatonin can be protective in this setting.
PubMed: 38725150
DOI: 10.1111/acel.14185