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Dwight E Bergles - One of the best experts on this subject based on the ideXlab platform.
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purinergic signaling controls spontaneous activity in the Auditory System throughout early development
The Journal of Neuroscience, 2021Co-Authors: Travis A Babola, Zhirong Wang, Calvin J Kersbergen, Ana Belen Elgoyhen, Thomas M Coate, Dwight E BerglesAbstract:Spontaneous bursts of electrical activity in the developing Auditory System arise within the cochlea before hearing onset and propagate through future sound-processing circuits of the brain to promote maturation of Auditory neurons. Studies in isolated cochleae revealed that this intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs), resulting in activation of purinergic autoreceptors, K+ efflux, and subsequent depolarization of inner hair cells. However, it is unknown when this activity emerges or whether different mechanisms induce activity during distinct stages of development. Here we show that spontaneous electrical activity in mouse cochlea from both sexes emerges within ISCs during the late embryonic period, preceding the onset of spontaneous correlated activity in inner hair cells and spiral ganglion neurons, which begins at birth and follows a base to apex developmental gradient. At all developmental ages, pharmacological inhibition of P2Y1 purinergic receptors dramatically reduced spontaneous activity in these three cell types. Moreover, in vivo imaging within the inferior colliculus revealed that Auditory neurons within future isofrequency zones exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased progressively during the postnatal prehearing period yet remained dependent on P2RY1. Analysis of mice with disrupted cholinergic signaling in the cochlea indicate that this efferent input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the Auditory System uses a consistent mechanism involving ATP release from ISCs and activation of P2RY1 autoreceptors to elicit coordinated excitation of neurons that will process similar frequencies of sound. SIGNIFICANCE STATEMENT In developing sensory Systems, groups of neurons that will process information from similar sensory space exhibit highly correlated electrical activity that is critical for proper maturation and circuit refinement. Defining the period when this activity is present, the mechanisms responsible and the features of this activity are crucial for understanding how spontaneous activity influences circuit development. We show that, from birth to hearing onset, the Auditory System relies on a consistent mechanism to elicit correlate firing of neurons that will process similar frequencies of sound. Targeted disruption of this activity will increase our understanding of how these early circuits mature and may provide insight into processes responsible for developmental disorders of the Auditory System.
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purinergic signaling controls spontaneous activity in the Auditory System throughout early development
bioRxiv, 2020Co-Authors: Travis A Babola, Zhirong Wang, Calvin J Kersbergen, Ana Belen Elgoyhen, Thomas M Coate, Dwight E BerglesAbstract:ABSTRACT Spontaneous bursts of electrical activity in the developing Auditory System arise within the cochlea prior to hearing onset and propagate through future sound processing circuits of the brain to promote maturation of Auditory neurons. Studies in isolated cochleae revealed that this intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs), resulting in activation of purinergic autoreceptors, K+ efflux and subsequent depolarization of inner hair cells (IHCs). However, little is known about when this activity emerges or whether different mechanisms underlie distinct stages of development. Here we show that spontaneous electrical activity in mouse cochlea emerges within ISCs during the late embryonic period, preceding the onset of spontaneous correlated activity in IHCs and spiral ganglion neurons (SGNs), which begins at birth and follows a base to apex developmental gradient. At all developmental stages, pharmacological inhibition of P2Y1 metabotropic purinergic receptors dramatically reduced spontaneous activity in these three cell types. Moreover, in vivo imaging within the inferior colliculus of awake mice revealed that Auditory neurons within future isofrequency zones exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased progressively during the postnatal prehearing period, yet remained dependent on P2RY1. Analysis of mice with disrupted cholinergic signaling in the cochlea, indicate that this input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the Auditory System uses a consistent mechanism involving ATP release from ISCs and activation of purinergic autoreceptors to elicit coordinated excitation of neurons that will process similar frequencies of sound. SIGNIFICANCE STATEMENT In developing sensory Systems, groups of neurons that will process information from similar sensory space exhibit highly correlated electrical activity that is critical for proper maturation and circuit refinement. Defining the period when this activity is present, the mechanisms responsible and the features of this activity are crucial for understanding how spontaneous activity influences circuit development. We show that, from birth to hearing onset, the Auditory System relies on a consistent mechanism to elicit correlate firing of neurons that will process similar frequencies of sound. Targeted disruption of this activity will increase our understanding of how these early circuits mature and may provide insight into processes responsible for developmental disorders of the Auditory System.
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homeostatic control of spontaneous activity in the developing Auditory System
Neuron, 2018Co-Authors: Travis A Babola, Alexandra Gribizis, Brian J Lee, John B Issa, Han Chin Wang, Michael C Crair, Dwight E BerglesAbstract:Summary Neurons in the developing Auditory System exhibit spontaneous bursts of activity before hearing onset. How this intrinsically generated activity influences development remains uncertain, because few mechanistic studies have been performed in vivo. We show using macroscopic calcium imaging in unanesthetized mice that neurons responsible for processing similar frequencies of sound exhibit highly synchronized activity throughout the Auditory System during this critical phase of development. Spontaneous activity normally requires synaptic excitation of spiral ganglion neurons (SGNs). Unexpectedly, tonotopic spontaneous activity was preserved in a mouse model of deafness in which glutamate release from hair cells is abolished. SGNs in these mice exhibited enhanced excitability, enabling direct neuronal excitation by supporting cell-induced potassium transients. These results indicate that homeostatic mechanisms maintain spontaneous activity in the pre-hearing period, with significant implications for both circuit development and therapeutic approaches aimed at treating congenital forms of deafness arising through mutations in key sensory transduction components.
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the origin of spontaneous activity in the developing Auditory System
Nature, 2007Co-Authors: Nicolas X Tritsch, Jonathan E Gale, Elisabeth Glowatzki, Dwight E BerglesAbstract:Spontaneous activity in the developing Auditory System is required for neuronal survival as well as the refinement and maintenance of tonotopic maps in the brain. However, the mechanisms responsible for initiating Auditory nerve firing in the absence of sound have not been determined. Here we show that supporting cells in the developing rat cochlea spontaneously release ATP, which causes nearby inner hair cells to depolarize and release glutamate, triggering discrete bursts of action potentials in primary Auditory neurons. This endogenous, ATP-mediated signalling synchronizes the output of neighbouring inner hair cells, which may help refine tonotopic maps in the brain. Spontaneous ATP-dependent signalling rapidly subsides after the onset of hearing, thereby preventing this experience-independent activity from interfering with accurate encoding of sound. These data indicate that supporting cells in the organ of Corti initiate electrical activity in Auditory nerves before hearing, pointing to an essential role for peripheral, non-sensory cells in the development of central Auditory pathways.
Walter H Backes - One of the best experts on this subject based on the ideXlab platform.
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lateralization connectivity and plasticity in the human central Auditory System
NeuroImage, 2005Co-Authors: Dave R M Langers, Pim Van Dijk, Walter H BackesAbstract:Although it is known that responses in the Auditory cortex are evoked predominantly contralateral to the side of stimulation, the lateralization of responses at lower levels in the human central Auditory System has hardly been studied. Furthermore, little is known on the functional interactions between the involved processing centers. In this study, functional MRI was performed using sound stimuli of varying left and right intensities. In normal hearing subjects, contralateral activation was consistently detected in the temporal lobe, thalamus and midbrain. Connectivity analyses showed that Auditory information crosses to the contralateral side in the lower brainstem followed by ipsilateral signal conduction towards the Auditory cortex, similar to the flow of Auditory signals in other mammals. In unilaterally deaf subjects, activation was more symmetrical for the cortices but remained contralateral in the midbrain and thalamus. Input connection strengths were different only at cortical levels, and there was no evidence for plastic reorganization at subcortical levels.
Alai Dabdoub - One of the best experts on this subject based on the ideXlab platform.
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reprogramming glia into neurons in the peripheral Auditory System as a solution for sensorineural hearing loss lessons from the central nervous System
Frontiers in Molecular Neuroscience, 2018Co-Authors: Steve J Meas, Chun Li Zhang, Alai DabdoubAbstract:Disabling hearing loss affects over 5% of the world's population and impacts the lives of individuals from all age groups. Within the next three decades, the worldwide incidence of hearing impairment is expected to double. Since a leading cause of hearing loss is the degeneration of primary Auditory neurons (PANs), the sensory neurons of the Auditory System that receive input from mechanosensory hair cells in the cochlea, it may be possible to restore hearing by regenerating PANs. A direct reprogramming approach can be used to convert the resident spiral ganglion glial cells into induced neurons to restore hearing. This review summarizes recent advances in reprogramming glia in the CNS to suggest future steps for regenerating the peripheral Auditory System. In the coming years, direct reprogramming of spiral ganglion glial cells has the potential to become one of the leading biological strategies to treat hearing impairment.
Dianne Durham - One of the best experts on this subject based on the ideXlab platform.
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reversible conductive hearing loss restored activity in the central Auditory System
Audiology and Neuro-otology, 2009Co-Authors: Kendall A Hutso, Dianne Durham, Debara L TucciAbstract:The effect of a reversible, unilateral hearing loss on 2-deoxyglucose (2-DG) uptake in the central Auditory System was studied using young gerbils. All animals had a unilateral conductive hearing loss (CHL), induced by atresia, on postnatal day 21 (P21). One week later, on P28, animals had their atresia repaired (CHL/R), or not repaired (CHL/NR), and CHL/NR animals entered the 2-DG experiments. CHL/R animals were allowed a 1-week period of restored binaural hearing experience prior to entering 2-DG experiments on P35. Animals in each group were injected with 2-DG and exposed to ambient sounds for 45 min prior to sacrifice. Uptake of 2-DG was measured in the anteroventral cochlear nucleus (AVCN), the medial superior olive (MSO), and the inferior colliculus (IC) on both sides of the brain. In CHL/NR animals, there were significant differences in uptake between the AVCN, MSO, and IC ipsilateral versus contralateral to the manipulated ear, indicating an imbalance in ascending afferent activity. In CHL/R animals, there were no significant differences, suggesting that 1 week after CHL repair, the appearance of balanced afferent activity had been restored.
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effects of conductive hearing loss on gerbil central Auditory System activity in silence
Hearing Research, 2001Co-Authors: Debara L Tucci, Dianne DurhamAbstract:Animal models of conductive hearing loss (CHL) show altered structure and function in the central Auditory System (CAS), particularly following unilateral deprivation. Assessment of neuronal activity as measured by 2-deoxyglucose (2-DG) uptake following CHL has been reported by two groups of investigators, with different findings. Woolf and colleagues [Brain Res. 274 (1983) 119] found that 2-DG uptake increased in the cochlear nucleus ipsilateral to the CHL, while Tucci et al. [Laryngoscope 109 (1999) 1359] found a decrease in 2-DG uptake in the ipsilateral cochlear nucleus. One significant difference between the protocols in the two studies was that, in the first study, animals were maintained in silence following 2-DG injection, whereas in the Tucci et al. study, animals were exposed to sound. The current study was designed to replicate the protocol used by Woolf et al. Young adult gerbils underwent unilateral malleus removal with bilateral canal ligation (n=6) or a sham procedure (n=7) 48 h prior to 2-DG administration and sacrifice. Optical density measurements were made from CAS nuclei. 2-DG uptake decreased in the ipsilateral cochlear nucleus and contralateral inferior colliculus, and in nuclei of the superior olivary complex bilaterally, supporting the finding that CHL is associated with a decrease in CAS neuronal activity.
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conductive hearing loss results in a decrease in central Auditory System activity in the young gerbil
Laryngoscope, 1999Co-Authors: Debara L Tucci, Dianne DurhamAbstract:Objectives/Hypothesis: The impact of childhood conductive HL (CHL) on development of Auditory function has long been debated. The present study was conducted to define and compare the consequences of CHL and cochlear ablation (CA) in young and adult animals, using 2-deoxyglucose (2-DG) uptake as a measure of metabolic activity. It was hypothesized that, for both ages, CHL would result in a decrease in activity in the major ascending central Auditory System pathway of the manipulated ear, but that this decrease would be significantly less than that observed with CA. Study Design: Shamcontrolled study of metabolic effects of CHL during sound stimulation. Methods: Gerbils (aged 21 days or adult), underwent malleus removal, CA, or a sham procedure. Young animals survived either 48 hours or 3 weeks; adults survived 3 weeks. Each age/survival CHL group contained eight animals; otherwise, each group (CA and sham) contained five animals, for a total number of 54. At the appropriate survival time, animals were given an intracardiac injection of 14 C-2-DG, and sacrificed under anesthesia after 45 minutes of exposure to normal laboratory sounds. Tissue sections were prepared for exposure to x-ray film for optical density measurements, and alternate sections stained for identification of nuclei. Measurements from Auditory nuclei of experimental animals were corrected against an unaffected control area (abducens nucleus) and compared with measurements taken from animals in the sham group. Auditory evoked potential thresholds to both air- and bone-conducted stimuli were obtained in a second group of neonatal and adult animals. Results: Both CHL and CA resulted in a marked decrease in 2-DG uptake in the major ascending projection of the manipulated ear, in both the neonatal and adult animals. In young animals, effects of CHL and CA were similar. Effects of CHL in adult animals were less marked and significantly different from either effects of CHL in young animals or effects of CA in adult animals. HL following malleus removal only was purely conductive and ranged from 38 to 55 dB across frequency. Conclusions : Results suggest that, particularly in young animals, a unilateral CHL may have profound effects on metabolic activity in the central Auditory System.
Kevin R Sitek - One of the best experts on this subject based on the ideXlab platform.
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mapping the human subcortical Auditory System using histology postmortem mri and in vivo mri at 7t
eLife, 2019Co-Authors: Kevin R Sitek, Omer Faruk Gulban, Evan Calabrese, Allan G Johnson, Agustin Lagecastellanos, Michelle Moerel, Satrajit S Ghosh, Federico De MartinoAbstract:Studying the human subcortical Auditory System non-invasively is challenging due to its small, densely packed structures deep within the brain. Additionally, the elaborate three-dimensional (3-D) structure of the System can be difficult to understand based on currently available 2-D schematics and animal models. Wfe addressed these issues using a combination of histological data, post mortem magnetic resonance imaging (MRI), and in vivo MRI at 7 Tesla. We created anatomical atlases based on state-of-the-art human histology (BigBrain) and postmortem MRI (50 µm). We measured functional MRI (fMRI) responses to natural sounds and demonstrate that the functional localization of subcortical structures is reliable within individual participants who were scanned in two different experiments. Further, a group functional atlas derived from the functional data locates these structures with a median distance below 2 mm. Using diffusion MRI tractography, we revealed structural connectivity maps of the human subcortical Auditory pathway both in vivo (1050 µm isotropic resolution) and post mortem (200 µm isotropic resolution). This work captures current MRI capabilities for investigating the human subcortical Auditory System, describes challenges that remain, and contributes novel, openly available data, atlases, and tools for researching the human Auditory System.
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mapping the human subcortical Auditory System using histology post mortem mri and in vivo mri at 7t
bioRxiv, 2019Co-Authors: Kevin R Sitek, Omer Faruk Gulban, Evan Calabrese, Allan G Johnson, Agustin Lagecastellanos, Michelle Moerel, Satrajit S Ghosh, Federico De MartinoAbstract:Studying the human subcortical Auditory System non-invasively is challenging due to its small, densely packed structures deep within the brain. Additionally, the System9s elaborate 3-D structure can be difficult to understand with available 2-D schematics and animal models. We addressed these issues using histology, post mortem MRI, and in vivo 7-Tesla MRI. We created anatomical atlases with state-of-the-art human histology and post mortem MRI (50μm). We measured functional MRI responses to natural sounds and demonstrate that functional localization of subcortical structures is reliable within individuals across different experiments. Further, the derived group functional atlas locates these structures within 2mm. Using diffusion MRI tractography, we revealed subcortical Auditory structural connectivity maps in vivo (1050μm isotropic resolution) and post mortem (200μm). This work captures current MRI capabilities for investigating the human subcortical Auditory System, describes challenges that remain, and contributes novel, public data, atlases, and tools for researching the human Auditory System.