The refinement of neural circuits towards mature function is driven during development by patterned spontaneous calcium-dependent electrical activity. In the auditory system, this sensory-independent activity arises in the pre-hearing cochlea and regulates the survival and refinement of the auditory pathway. However, the origin and interplay of calcium signals during cochlear development is unknown in vivo. Here we show how calcium dynamics in the cochlear neuroepithelium of live pre-hearing mice shape the activity of the inner hair cells (IHCs) and their afferent synapses. Both IHCs and supporting cells (SCs) generate spontaneous calcium-dependent activity. Calcium waves from SCs synchronise the activity of nearby IHCs, which then spreads longitudinally recruiting several additional IHCs via a calcium wave-independent mechanism. This synchronised IHC activity in vivo increases the probability of afferent terminal recruitment. Moreover, the modiolar-to-pillar segregation in sound sensitivity of mature auditory nerve fibres appears to be primed at pre-hearing ages.
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http://dx.doi.org/10.1038/s41467-024-55519-w | DOI Listing |
Nat Commun
January 2025
School of Biosciences, University of Sheffield, Sheffield, S10 2TN, UK.
The refinement of neural circuits towards mature function is driven during development by patterned spontaneous calcium-dependent electrical activity. In the auditory system, this sensory-independent activity arises in the pre-hearing cochlea and regulates the survival and refinement of the auditory pathway. However, the origin and interplay of calcium signals during cochlear development is unknown in vivo.
View Article and Find Full Text PDFElife
December 2024
Experimental Otology Group, InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany.
To encode continuous sound stimuli, the inner hair cell (IHC) ribbon synapses utilize calcium-binding proteins (CaBPs), which reduce the inactivation of their Ca1.3 calcium channels. Mutations in the gene underlie non-syndromic autosomal recessive hearing loss DFNB93.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, State University of Ceará, 1700. Dr Silas Munguba Av., 60455-900, Fortaleza, Ceará, Brazil. Electronic address:
The failure of achieving a penile erection for satisfactory sexual intercourse is known as erectile dysfunction (ED). The primary mediator for penile erection is nitric oxide (NO). ED is often associated with endothelial/nitrergic dysfunction characterized by a reduction of the bioavailability of NO.
View Article and Find Full Text PDFCirculation
December 2024
Department of Internal Medicine (Q.S., J.W., H.M., X.L., J. Streeter, J. Sharafuddin, E.W., B.C., D.H., L.-S.S., E.D.A.), Carver College of Medicine, University of Iowa, Iowa City.
Background: The docking protein IRS2 (insulin receptor substrate protein-2) is an important mediator of insulin signaling and may also regulate other signaling pathways. Murine hearts with cardiomyocyte-restricted deletion of (cIRS2-KO) are more susceptible to pressure overload-induced cardiac dysfunction, implying a critical protective role of IRS2 in cardiac adaptation to stress through mechanisms that are not fully understood. There is limited evidence regarding the function of IRS2 beyond metabolic homeostasis regulation, particularly in the context of cardiac disease.
View Article and Find Full Text PDFInt J Mol Sci
May 2024
Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan.
The excessive activation of frog eggs, referred to as overactivation, can be initiated by strong oxidative stress, leading to expedited calcium-dependent non-apoptotic cell death. Overactivation also occurs spontaneously, albeit at a low frequency, in natural populations of spawned frog eggs. Currently, the cytological and biochemical events of the spontaneous process have not been characterized.
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