Biology subjects

Ceriani, F.

Publications and source records attributed to Ceriani, F..

6 recordsLinked to original sources

bioRxiv2024

An Open-Source Deep Learning-Based GUI Toolbox For Automated Auditory Brainstem Response Analyses (ABRA)

Hearing loss is a pervasive global health challenge with profound impacts on communication, cognitive function, and quality of life. Recent studies have established age-related hearing loss as a significant risk factor for dementia, highlighting the importance of hearing loss research. Auditory brainstem responses (ABRs), which are electrophysiological recordings of acoustically evoked synchronized neural activity from the auditory nerve and brainstem, serve as in vivo correlates for sensory hair cell and synaptic function, hearing sensitivity, and other critical readouts of auditory pathway physiology, making them highly valuable for both basic neuroscience and clinical research. Despite their utility, traditional ABR analyses rely heavily on subjective manual interpretation, which may introduce variability and pose challenges for reproducibility across studies. Here, we introduce Auditory Brainstem Response Analyzer (ABRA), a novel suite of open-source ABR analysis tools powered by deep learning, which automates and standardizes ABR waveform analysis. ABRA employs convolutional neural networks trained on diverse datasets collected from multiple experimental settings, achieving rapid and unbiased extraction of key ABR metrics, including peak amplitude, latency, and auditory threshold estimates. We demonstrate that ABRAs deep learning models provide performance comparable to expert human annotators while dramatically reducing analysis time and enhancing reproducibility across datasets from different laboratories. By bridging hearing research, sensory neuroscience, and advanced computational techniques, ABRA facilitates broader interdisciplinary insights into auditory function. An online version of the tool is available for use at no cost at https://abra.ucsd.edu.

neuroscience↗

bioRxiv2023

Organismal landscape of clock cells and circadian gene expression in Drosophila

BackgroundCircadian rhythms time physiological and behavioral processes to 24-hour cycles. It is generally assumed that most cells contain self-sustained circadian clocks that drive circadian rhythms in gene expression that ultimately generating circadian rhythms in physiology. While those clocks supposedly act cell autonomously, current work suggests that in Drosophila some of them can be adjusted by the brain circadian pacemaker through neuropeptides, like the Pigment Dispersing Factor (PDF). Despite these findings and the ample knowledge of the molecular clockwork, it is still unknown how circadian gene expression in Drosophila is achieved across the body. ResultsHere, we used single-cell and bulk RNAseq data to identify cells within the fly that express core-clock components. Surprisingly, we found that less than a third of the cell types in the fly express core-clock genes. Moreover, we identified Lamina wild field (Lawf) and Ponx-neuro positive (Poxn) neurons as putative new circadian neurons. In addition, we found several cell types that do not express core clock components but are highly enriched for cyclically expressed mRNAs. Strikingly, these cell types express the PDF receptor (Pdfr), suggesting that PDF drives rhythmic gene expression in many cell types in flies. Other cell types express both core circadian clock components and Pdfr, suggesting that in these cells, PDF regulates the phase of rhythmic gene expression. ConclusionsTogether, our data suggest three different mechanisms generate cyclic daily gene expression in cells and tissues: canonical endogenous canonical molecular clock, PDF signaling-driven expression, or a combination of both.

molecular biology↗

bioRxiv2023

Oncomodulin Regulates Spontaneous Calcium Signaling and Maturation of Afferent Innervation in Cochlear Outer Hair Cells

Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca2+ activity in both sensory and non-sensory cells. Calcium signaling in neonatal OHCs can be modulated by Oncomodulin (OCM, {beta}-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca2+ activity and afferent connectivity during development. Using a genetically encoded Ca2+ sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm+/+) and Ocm knockout (Ocm-/-) littermates, we found increased spontaneous Ca2+ activity and upregulation of purinergic receptors in OHCs from GCaMP6s Ocm-/- cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibers on GCaMP6s Ocm-/- OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca2+ signaling in the developing cochlea and the maturation of OHC afferent innervation.

developmental biology↗

bioRxiv2022

Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells.

In cochlear outer hair cells (OHCs), a network of Ca2+ channels, pumps and Ca2+-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), -parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm-/-) gives rise to progressive cochlear dysfunction in young adult mice. Here, we show that changes in Ca2+ signaling begin early in postnatal development of Ocm-/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca2+ transients in OHCs and leads to slower KCl-induced Ca2+ transients than those elicited in cells from Ocm-/- littermates. We compared OCM buffering kinetics with other CaBPs in animal models and cultured cells. In a double knockout of Ocm and Apv (Ocm-/-;Apv-/-), mutant OHCs show even faster Ca2+ kinetics, suggesting that APV may also contribute to early postnatal Ca2+ signaling. In transfected HEK293T cells, OCM slows Ca2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca2+ environment by lowering the amount of freely available [Ca2+]i in OHCs and in transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca2+ signals through its inimitable Ca2+ buffering capacity.

developmental biology↗

bioRxiv2019

Dynamic coupling of cochlear inner hair cell intrinsic Ca2+ action potentials to Ca2+ signaling of non-sensory cells

The relationship between Ca2+ action potential (AP) activity in immature inner hair cells (IHCs) and the spontaneous ATP-dependent intercellular Ca2+ signaling in cochlear non-sensory cells (NSCs) of the greater epithelial ridge (GER) is unclear. Here, we determined that IHCs fired asynchronous Ca2+ APs also in the absence of Ca2+ activity in the GER. Patch clamp recordings from IHCs isolated from the rest of the sensory epithelium confirmed that this firing activity is an intrinsic property of immature IHCs. However, frequency, correlation index and burst duration of IHC APs increased significantly during Ca2+ wave propagation in NSCs, and depended on wave extension in the GER. Furthermore, IHC depolarization under whole cell patch clamp conditions triggered Ca2+ signals in nearby NSCs with a delay that was proportional to the distance from the stimulated IHC. Thus the immature mammalian cochlea supports bidirectional exchange of Ca2+ signals between IHCs and NSCs.\n\nIMPACT STATEMENTIn inner hair cells of the developing mammalian cochlea, Ca2+ action potentials are both intrinsic and bidirectionally coupled to the ATP-dependent Ca2+ signaling of the surrounding non-sensory cells.

developmental biology↗

bioRxiv2018

Spontaneous and coordinated Ca2+ activity of cochlear sensory and non-sensory cells drives the maturation of OHC afferent innervation

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca2+ signalling in vivo, through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca2+ signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca2+ spikes during a narrow period of immature development. Simultaneously, waves of Ca2+ activity in the non-sensory greater epithelial ridge act, via ATP-induced activation of P2X receptors, to synchronize OHC firing, resulting in the refinement of their afferent innervation. In the absence of connexin channels Ca2+ waves are impaired, leading to a reduction in the number of ribbon synapses and afferent fibres on OHCs. We propose that the correct maturation of the afferent connectivity in OHCs requires experience-independent Ca2+ signals from sensory and non-sensory cells.

neuroscience↗