Search Results (134)

Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors. Full article

Background: Kölliker’s organ (KO), a transient structure in the cochlea, plays a critical role in the auditory maturation of mammals, particularly during embryonic and early postnatal development. This organ is essential for the proper differentiation and function of cochlear cells, acting as a pivotal source of signalling molecules that influence hair cell development and synaptic connectivity. Methods: This study systematically analyses the literature according to the PRISMA statement in order to evaluate the function roles of KO during cochlea development, reporting the molecular mechanisms and signalling pathways involved. Results: From our study, it emerged that KO supporting cells release adenosine triphosphate (ATP) through connexin hemichannels, initiating a cascade of intracellular calcium (Ca²⁺) signalling in adjacent inner hair cells (IHCs). This signalling promotes the release of glutamate, facilitating synaptic excitation of afferent nerve fibres and enhancing auditory neuron maturation prior to the onset of hearing. Additionally, the spontaneous electrical activity generated within KO supports the establishment of essential neural connections in the auditory pathway. The dynamic interplay between ATP release, Ca²⁺ signalling, and morphological changes in KO is crucial for cochlear compartmentalisation and fluid regulation, contributing to the formation of endolymph and perilymph. Furthermore, KO supports cellular plasticity and may provide a reservoir of precursor cells capable of trans-differentiating into hair cells under specific conditions. Conclusions: Dysregulation of KO function or delayed degeneration of its supporting cells has been implicated in auditory disorders, underscoring the importance of this organ in normal cochlear development and auditory function. Despite its identification over a century ago, further investigation is necessary to elucidate the molecular mechanisms underlying KO’s contributions to auditory maturation, particularly in human physiology. Full article

In the era of artificial intelligence, the demand for rapid and efficient data processing is growing, and traditional computing architectures are increasingly struggling to meet these needs. Against this backdrop, memristor devices, capable of mimicking the computational functions of brain neural networks, have emerged as key components in neuromorphic systems. Despite this, memristors still face many challenges in biomimetic functionality and circuit integration. In this context, a starch–glycerol-based hydrogel memristor was developed using starch as the dielectric material. The starch–glycerol–water mixture employed in this study has been widely recognized in literature as a physically cross-linked hydrogel system with a three-dimensional network, and both high water content and mechanical flexibility. This memristor demonstrates a high current switching ratio and stable threshold voltage, showing great potential in mimicking the activity of biological neurons. The device possesses the functionality of auditory neurons, not only achieving artificial spiking neuron discharge but also accomplishing the spatiotemporal summation of input information. In addition, we demonstrate the application capabilities of this artificial auditory neuron in gain modulation and in the synchronization detection of sound signals, further highlighting its potential in neuromorphic engineering applications. These results suggest that starch-based hydrogel memristors offer a promising platform for the construction of bio-inspired auditory neuron circuits and flexible neuromorphic systems. Full article

Background/Objectives: A maternal high-fat diet (HFD) impairs brain structure in offspring. In turn, fish oil (FO) rich in n-3 polyunsaturated fatty acids (PUFAs) has neuroprotective effects. Therefore, we investigated whether maternal HFD exposure affected the neurological reflexes, neuron morphology, and n-3 PUFA levels in the cerebral cortex of the offspring and whether these effects were mitigated by maternal FO consumption. Methods: Female Sprague Dawley rats received a control diet (CD, 10% Kcal fat) or HFD (45% Kcal fat) five weeks before mating and throughout pregnancy and lactation. From mating, a subgroup of HFD was supplemented with 11.4% FO into the diet (HFD-FO). Neurological reflexes were evaluated from postnatal day (PND) 3 until PND20. Brains were removed at PND22 for neuron morphology analysis. Moreover, fatty acid composition and transcripts of genes encoding for factors associated with synapse transmission (SNAP-25), plasticity (BDNF), transport of DHA (MFSD2a), and inflammation (NF-κB and IL-1β) were quantified in prefrontal, motor, and auditory cortices. Results: FO diminished the effects of HFD on the number of thin and mushroom-shaped dendritic spines in the cerebral cortex in both sexes. It also reversed the HFD effects on the motor and auditory reflexes in female and male offspring, respectively. In males, FO up-regulated Bdnf transcript levels in the motor cortex compared with CD and HFD. In females, n-3 PUFAs were higher in HFD and HFD-FO than in CD in the auditory cortex. Conclusions: Our results highlight the protective role of maternal dietary n-3 PUFAs in counteracting the effects induced by HFD on the acquisition of neurological reflexes and neuronal morphology in the cerebral cortex of the offspring of both sexes. Full article

Repulsive guidance molecule-a (RGMa) has emerged as a significant therapeutic target in a variety of neurological disorders, including neurodegenerative diseases and acute conditions. This review comprehensively examines the multifaceted role of RGMa in central nervous system (CNS) pathologies such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, neuromyelitis optica spectrum disorder, spinal cord injury, stroke, vascular dementia, auditory neuropathy, and epilepsy. The mechanisms through which RGMa contributes to neuroinflammation, neuronal degeneration, and impaired axonal regeneration are herein discussed. Evidence from preclinical studies associate RGMa overexpression with negative outcomes, such as increased neuroinflammation and synaptic loss, while RGMa inhibition, particularly the use of agents like elezanumab, has shown promise in enhancing neuronal survival and functional recovery. RGMa’s responses concerning immunomodulation and neurogenesis highlight its potential as a therapeutic avenue. We emphasize RGMa’s critical role in CNS pathology and its potential to pave the way for innovative treatment strategies in neurological disorders. While preclinical findings are encouraging so far, further clinical trials are needed to validate the safety and efficacy of RGMa-targeted therapies. Full article

Epilepsy is a multifaceted neurological disorder characterized by recurrent seizures and associated with molecular and immune alterations in key brain regions. The GASH/Sal (Genetic Audiogenic Seizure Hamster, Salamanca), a genetic model for audiogenic epilepsy, provides a powerful tool to study seizure mechanisms and resistance in predisposed individuals. This study investigates the proteomic and immune responses triggered by audiogenic kindling in the inferior colliculus, comparing non-responder animals exhibiting reduced seizure severity following repeated stimulation versus GASH/Sal naïve hamsters. To assess auditory pathway functionality, Auditory Brainstem Responses (ABRs) were recorded, revealing reduced neuronal activity in the auditory nerve of non-responders, while central auditory processing remained unaffected. Cytokine profiling demonstrated increased levels of proinflammatory markers, including IL-1 alpha (Interleukin-1 alpha), IL-10 (Interleukin-10), and TGF-beta (Transforming Growth Factor beta), alongside decreased IGF-1 (Insulin-like Growth Factor 1) levels, highlighting systemic inflammation and its interplay with neuroprotection. Building on these findings, a proteomic analysis identified 159 differentially expressed proteins (DEPs). Additionally, bioinformatic approaches, including Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co-expression Network Analysis (WGCNA), revealed disrupted pathways related to metabolic and inflammatory epileptic processes and a module potentially linked to a rise in the threshold of seizures, respectively. Differentially expressed genes, identified through bioinformatic and statistical analyses, were validated by RT-qPCR. This confirmed the upregulation of six genes (Gpc1—Glypican-1; Sdc3—Syndecan-3; Vgf—Nerve Growth Factor Inducible; Cpne5—Copine 5; Agap2—Arf-GAP with GTPase domain, ANK repeat, and PH domain-containing protein 2; and Dpp8—Dipeptidyl Peptidase 8) and the downregulation of two (Ralb—RAS-like proto-oncogene B—and S100b—S100 calcium-binding protein B), aligning with reduced seizure severity. This study may uncover key proteomic and immune mechanisms underlying seizure susceptibility, providing possible novel therapeutic targets for refractory epilepsy. Full article

Proteins involved in synaptic transmission in normal hearing, acoustic stimulation, and tinnitus were identified using protein–protein interaction (PPI) networks. The gene list for tinnitus was compiled from the GeneCards database using the keywords “synaptic transmission” AND “inferior colliculus” AND “tinnitus” (Tin). For comparison, two gene lists were built using the keywords “auditory perception” (AP) and “acoustic stimulation” (AS). The STRING and the Cytoscape data analyzer were used to identify the top two high-degree proteins (HDPs) and the corresponding high-score interaction proteins (HSIP). The top1 key proteins of the AP and AS processes are BDNF and the receptor NTRK2; the top2 key proteins in the AP process are PVALB, together with GAD1, CALB1, and CALB2, which are important for the balance of excitation and inhibition. In the AS process, the top2 key proteins are FOS, CREB1, EGR1, and MAPK1, reflecting an activated state. The top1 key proteins of the Tin process are BDNF, NTRK3, and NTF3; these proteins are associated with the proliferation and differentiation of neurons and indicate the remodeling of synaptic transmission in IC. The top2 key proteins are GFAP and S100B, indicating a role for astrocytes in the modulation of synaptic transmission. Full article

Echolocation represents one of the most rapid adaptive sensorimotor modulation behaviors observed in mammals, establishing bats as one of the most evolutionarily successful mammals. Bats rely on high-frequency hearing for survival, but our understanding of its cellular molecular basis is scattered and segmented. Herein, we constructed the first single-cell transcriptomic landscape of the cochlea in Hipposideros armiger, a CF-FM bat, using a PacBio-optimized genome and compared it with the results obtained from unoptimized original genomes. Sixteen distinct cell types were distributed across five spatial regions of the cochlea. Notably, through hematoxylin and eosin staining and fluorescence in situ hybridization, we identified new types of spiral ganglion neuron (SGN) cells in the cochlea of H. armiger. These SGN cells are likely critical for auditory perception and may have driven the adaptive evolution of high-frequency hearing in this species. Furthermore, we uncovered the differentiation relationships of among specific cell types, such as the transition from supporting cells to hair cells. Using the cochlear cell atlas as a reference, cell types susceptible to deafness-associated genes (in the human) were also identified. In summary, this study provides novel insights into the cellular and molecular mechanisms underlying the adaptive high-frequency hearing in bats and highlights potential candidate cell types and genes for therapeutic interventions in hearing loss. Full article

Background: This study investigates electrophysiological distinctions in auditory evoked potentials (AEPs) among individuals with chronic subjective tinnitus, with a specific focus on the impact of treatment response and tinnitus localisation. Methods: Early AEPs, known as Auditory Brainstem Responses (ABR), and middle AEPs, termed Auditory Middle Latency Responses (AMLR), were analysed in tinnitus patients across four clinical centers in an attempt to verify increased neuronal activity, in accordance with the current tinnitus models. Our statistical analyses primarily focused on discrepancies in time–domain core features of ABR and AMLR signals, including amplitudes and latencies, concerning both treatment response and tinnitus laterality. Results: Statistically significant differences were observed in ABR wave III and V latencies, ABR wave III peak amplitude, and AMLR wave Na and Nb amplitudes when comparing groups based on their response to treatment, accompanied by varying effect sizes. Conversely, when examining groups categorised by tinnitus laterality, no statistically significant differences emerged. Conclusions: These results provide valuable insights into the potential influence of treatment responses on AEPs. However, further research is imperative to attain a comprehensive understanding of the underlying mechanisms at play. Full article

Background: The ionotropic glutamate receptor AMPA (AMPAR) mediates fast excitatory synaptic transmission and regulates synaptic strength in various parts of the CNS. Emotional challenges can affect these processes by influencing AMPAR levels and localization via stress hormones, resulting, e.g., in behavioral changes. AMPARs are essential for auditory processing, but their response to stress hormones in the central or peripheral auditory system remains poorly understood. Therefore, this scoping review examines the effects of corticosterone (CORT), a primary stress hormone in rodents, on AMPA receptor levels and localization in the rodent nervous system and considers potential implications for the auditory system. Methods: We systematically searched PubMed, Web of Science, and OVID EMBASE using MeSH terms related to AMPA receptors and corticosterone. Studies were screened based on predefined inclusion criteria, including original research published in English that focused on AMPA receptor subunits (e.g., GluR1-4, GluA1-4, Gria1-4). Of 288 articles screened, 17 met the criteria for final analysis. Results: No reports were found regarding CORT action in the auditory system. Three main experimental models used in the included research were identified: neuronal cultures, isolated tissue cultures, and animal models. Generally, short-term CORT exposure increases AMPAR surface localization and mobility in neuronal cultures, especially in the hippocampus and prefrontal cortex. However, results from animal models were inconsistent due to variations in experimental design and other factors. The isolated tissue study did not provide sufficient data for clear conclusions. Conclusions: Variability in experimental models limits our ability to draw definitive conclusions about the effects of CORT on AMPARs across different regions of the nervous system. The differences in live animal studies highlight the need for standardized methods and reporting. Since AMPARs play a crucial role in auditory processing, CORT-induced changes in neuronal cultures may occur in the auditory system. Further research is needed to explore the specific responses of AMPAR subunits and how stress hormones may influence auditory disorders, which could help identify potential treatment strategies. Full article

Neonatal hyperbilirubinemia may result in long-lasting motor, auditory and learning impairments. The mechanisms responsible for the localization of unconjugated bilirubin (UCB) to specific brain areas as well as those involved in potentially permanent central nervous system (CNS) dysfunctions are far from being clear. One area of investigation includes exploring how hyperbilirubinemia determines neuronal alterations predisposing to neurodevelopmental disorders. We focused on the hippocampus and pyramidal cell dysregulation of calcium homeostasis and synaptic activity, with a particular focus on early forms of correlated network activity, i.e., giant depolarizing potentials (GDPs), crucially involved in shaping mature synaptic networks. We performed live calcium imaging and patch clamp recordings from acute hippocampal slices isolated from wild-type rats exposed to exogenous high bilirubin concentration. We then explored the impact of endogenous bilirubin accumulation in hippocampal slices isolated from a genetic model of hyperbilirubinemia, i.e., Gunn rats. Our data show in both models an age-dependent dysregulation of calcium dynamics accompanied by severe alterations in GDPs, which were strongly reduced in hippocampal slices of hyperbilirubinemic rats, where the expression of GABAergic neurotransmission markers was also altered. We propose that hyperbilirubinemia damages neurons and affects the refinement of GABAergic synaptic circuitry during a critical period of hippocampal development. Full article

Background: Previous studies have shown that multiple post-traumatic irradiations of the cochlea with near-infrared light (NIR) can significantly reduce noise-induced hearing loss. However, a single NIR pre-treatment was shown to have the same effect. Extending the pre-treatment time did not result in any further reduction in hearing loss. The present study investigated whether a combined NIR pre- and post-treatment had an increased effect on hearing preservation. Methods: Frequency-specific auditory brainstem potential thresholds (ABR) were determined in young adult mice. One group (n = 8) underwent NIR irradiation (808 nm, 120 mW, 15 min) of the cochlea, followed by a 30 min noise exposure (5–20 kHz, 115 dB SPL). A post-NIR treatment was administered for 30 min immediately following the noise trauma. After 14 days, hearing loss was determined by ABR measurements. The results were compared with a trauma-only group (n = 8) and an untreated control group (n = 5). Subsequently, the spiral ganglion neuron density was investigated. Results: A peri-traumatic NIR treatment resulted in a significantly lower hearing loss compared to the trauma-only group. Hearing protection in these animals significantly exceeded the effect of an exclusive pre- or post-treatment across all frequencies. A loss of spiral ganglion neurons in the trauma-only group was observed, which was significantly rescued by the peri-traumatic NIR treatment. Conclusions: A single peri-traumatic NIR treatment seems to be the more effective approach for the preservation of hearing thresholds after noise trauma compared to an isolated pre- or post-treatment. One target of the protective effect seems to be the spiral ganglion. Full article

The development of positioning systems has been significantly advanced by a combination of technological innovations, such as improved sensors, signal processing, and computational power, alongside inspiration drawn from biological mechanisms. Although vision is the main means for positioning oneself—or elements relative to oneself—in the environment, other sensory mediums provide additional information, and may even take over when visibility is lacking, such as in the dark or in troubled waters. In particular, the auditory system in mammals greatly contributes to determining the location of sound sources, as well as navigating or identifying objects’ texture and shape, when combined with echolocation behavior. Taking further inspiration from the neuronal processing in the brain, neuromorphic computing has been studied in the context of sound source localization and echolocation-based navigation, which aim at better understanding biological processes or reaching state-of-the-art performances in energy efficiency through the use of spike encoding. This paper sets out a review of these neuromorphic sound source localization, sonar- and radar-based navigation systems, from their earliest appearance to the latest published works. Current trends and possible future directions within this scope are discussed. Full article

Background/Objectives: Tinnitus is a debilitating auditory disorder commonly described as a ringing in the ears in the absence of an external sound source. Sound trauma is considered a primary cause. Neuronal hyperactivity is one potential mechanism for the genesis of tinnitus and has been identified in the cochlear nucleus (CN) and the auditory cortex (AC), where there may be an imbalance of excitatory and inhibitory neurotransmissions. However, no study has directly correlated tinnitus with the extracellular levels of amino acids in the CN and the AC using microdialysis, which reflects the functions of these neurochemicals. In the present study, rats were exposed to acoustic trauma and then subjected to behavioural confirmation of tinnitus after one month, followed by microdialysis. Methods: Rats were divided into sham (aged, n = 6; young, n = 6); tinnitus-positive (aged, n = 7; young, n = 7); and tinnitus-negative (aged, n = 3; young, n = 3) groups. In vivo microdialysis was utilized to collect samples from the CN and the AC, simultaneously, in the same rat. Extracellular levels of amino acids were quantified using high-performance liquid chromatography (HPLC) coupled with an electrochemical detector (ECD). The effects of sound stimulation and age on neurochemical changes associated with tinnitus were also examined. Results: There were no significant differences in either the basal levels or the sound stimulation-evoked changes of any of the amino acids examined in the CN and the AC between the sham and tinnitus animals. However, the basal levels of serine and threonine exhibited age-related alterations in the AC, and significant differences in threonine and glycine levels were observed in the responses to 4 kHz and 16 kHz stimuli in the CN. Conclusions: These results demonstrate the lack of a direct link between extracellular levels of amino acids in the CN and the AC and tinnitus perception in a rat model of tinnitus. Full article

Neurotrophins are proteins that mediate neuronal development using spatiotemporal signaling gradients. The chicken nucleus magnocellularis (NM), an analogous structure to the mammalian anteroventral cochlear nucleus, provides a model system in which signaling between the brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) is temporally regulated. In the NM, TrkB expression is high early in development (embryonic [E] day 9) and is downregulated until maturity (E18–21). It is currently unknown how BDNF–TrkB signaling affects neuronal properties throughout development and across a spatial (i.e., frequency) axis. To investigate this, we exogenously applied BDNF onto NM neurons ex vivo and studied intrinsic properties using whole-cell patch clamp electrophysiology. Early in development (E13), when TrkB expression is detectable with immunohistochemistry, BDNF application slowed the firing of high-frequency NM neurons, resembling an immature phenotype. Current measurements and biophysical modeling revealed that this was mediated by a decreased conductance of the voltage-dependent potassium channels. Interestingly, this effect was seen only in high-frequency neurons and not in low-frequency neurons. BDNF–TrkB signaling induced minimal changes in late-developing NM neurons (E20–21) of high and low frequencies. Our results indicate that normal developmental downregulation of BDNF–TrkB signaling promotes neuronal maturation tonotopically in the auditory brainstem, encouraging the appropriate development of neuronal properties. Full article