1,720,961 research outputs found
Pre- and postsynaptic recovery of semicircular canal activity in the frog following ototoxic insult
No full textAim: Inner ear hair cells of lower vertebrates regenerate following physical or chemical insults. In the present study we aimed to define the damage and recovery of the pre and postsynaptic activity in the frog crista ampullaris after ototoxic insult with the antibiotic, gentamicin.
Methods: Frogs were treated with a single dose of gentamicin sulphate (GM-5mM) administered intraotically. The presynaptic activity was monitored by recording in isolated canal preparations the endoampullar (receptor) potential (Adc). The postsynaptic activity was monitored by recording the resting (R) and evoked spike activity (E) from the whole ampullar nerve and from single canal afferents.
Results: We found that Adc was abolished 5 days after GM administration and that it progressively recovered close to control values 20 days after treatment. These results well fitted with the morphological damage and recovery of hair cells in the crista epithelium. Consistently with the presynaptic damage, the canal afferent activity was abolished 5 days after GM treatment, while the recovery of the background and the evoked afferent activity showed a different sequence. Background activity (R) was detected 7-8 days after GM treatment and it was not modulated by mechanical stimulation of the canal. In addition, R reached control values (14/15 days post-treatment), before those of the evoked activity (E-20 days post-treatment). Intracellular recordings confirmed the above mentioned results and revealed that the evoked EPSP discharge, together with the spike activity, reached normal values close to 20 days post-treatment.
Conclusion: The present results show that frog semicircular canal rapidly and completely recovers its pre -and postsynaptic function following severe ototoxic insult and that during the recovery, the synaptic function of regenerating hair cells becomes functional before the mechano-transduction function
Differential recovery of background and evoked afferent activity in the frog semicircular canal following ototoxic insult
No full textThe present study was aimed to define the damage and recovery of pre- and postsynaptic activity in the frog crista ampullaris after ototoxic insult with gentamicin (GM). We found that the endoampullar potential (receptor potential) recorded from the isolated canal was abolished 6 days after GM administration and that it recovered close to the control 20 days after treatment. Consistently with the presynaptic damage, the afferent activity from the ampullar nerve was abolished 6 days after GM treatment, while the recovery of background and evoked afferent activity showed a different sequence. Background activity reappeared 7-8 days after GM treatment and in this period it was not driven by canal mechanical stimulation. In addition, background activity reached control values around 15 days after the ototoxic insult, while the evoked activity was detected 9-10 days after GM treatment and appeared normal close to 20 days. Intracellular recordings from single canal afferents confirmed the above mentioned results. The present study show that the frog semicircular canal rapidly and completely recovers its pre -and postsynaptic function following severe ototoxic insult and that during the recovery afferent transmission at rest becomes functional before the mechano-transduction function
Electrophysiological evidence for potassium accumulation between type I hair cells and calyx terminal in mammalian crista ampullaris
Full text linkTwo types of hair cells are present in mammalian vestibular sensory epithelia, called Type I and Type II hair cells, which differ in electrophysiological properties and innervation. Type II hair cells are contacted by several bouton nerve terminals, while Type I hair cells are contacted by a calyx nerve terminal that envelopes the entire basolateral membrane. Only Type I hair cells, moreover, express a low-voltage activated outward K+ current, called IK,L, which confers upon them a much lower input resistance at rest compared to Type II hair cells. As a consequence, in Type I hair cells large transducer currents would be necessary to change the cell membrane potential and to depolarize the cell enough to activate voltage-gated Ca2+ channels and related neurotransmitter release. How the calyx synapse operates remains in fact enigmatic. It has been speculated that K+ accumulation in the synaptic cleft cooperates with conventional (vesicular) synaptic transmission in sustaining afferent transmission by Type I hair cells. By combining the patch-clamp whole-cell configuration with the whole crista preparation, we have recorded the current and voltage responses of mouse semicircular canal Type I and Type II hair cells in situ. Depolarizing voltage steps elicited in Type II hair cells a large outward K+ current characterized by a substantial time-dependent inactivation, while the same voltage-protocol elicited in most Type I hair cells a large and sustained outward K+ current. However, in a notable percentage (51%) of Type I hair cells investigated, the outward K+ current showed a substantial time-dependent relaxation. In these cells, moreover, upon repolarization to –40 mV the instantaneous current was inward, reversing to outward slowly with time. A reasonable explanation for the above results is that during large outward K+ currents, K+ accumulates around Type I hair cells, thus shifting the K+ reversal potential (VrevK+) toward more positive values. The rightward shift of VrevK+ would produce both the outward current relaxation during depolarizing voltage steps and the instantaneous inward current upon repolarization at –40 mV. Since we never observed such effects when recording from Type II hair cells, we hypothesized that the presence of a residual nerve calyx was responsible for K+ accumulation around Type I hair cells. We also found that by using voltage protocols that increased extracellular K+ accumulation, IK,L deactivation was slowed down. Similar results, i.e. VrevK+ rightward shift and IK,L deactivation slowdown, were obtained by local perfusion of the preparation with an extracellular solution enriched in K+, thus corroborating our hypothesis about K+ accumulation.
In conclusion, our results provide electrophysiological evidence for an increased K+ concentration in the synaptic cleft between Type I hair cell and its calyx ending during outward K+ current activation. The resulting depolarization might be aimed at reinforcing and prolonging Ca2+ channels activation and thus afferent transmission during slow head movements detected by vestibular organs
Intercellular K(+) accumulation depolarizes Type I vestibular hair cells and their associated afferent nerve calyx
No full textMammalian vestibular organs contain two types of sensory receptors, named Type I and Type II hair cells. While Type II hair cells are contacted by several small afferent nerve terminals, the basolateral surface of Type I hair cells is almost entirely enveloped by a single large afferent nerve terminal, called calyx. Moreover Type I, but not Type II hair cells, express a low-voltage-activated outward K(+) current, I(K,L), which is responsible for their much lower input resistance (Rm) at rest as compared to Type II hair cells. The functional meaning of I(K,L) and associated calyx is still enigmatic. By combining the patch-clamp whole-cell technique with the mouse whole crista preparation, we have recorded the current- and voltage responses of in situ hair cells. Outward K(+) current activation resulted in K(+) accumulation around Type I hair cells, since it induced a rightward shift of the K(+) reversal potential the magnitude of which depended on the amplitude and duration of K(+) current flow. Since this phenomenon was never observed for Type II hair cells, we ascribed it to the presence of a residual calyx limiting K(+) efflux from the synaptic cleft. Intercellular K(+) accumulation added a slow (τ>100ms) depolarizing component to the cell voltage response. In a few cases we were able to record from the calyx and found evidence for intercellular K(+) accumulation as well. The resulting depolarization could trigger a discharge of action potentials in the afferent nerve fiber. Present results support a model where pre- and postsynaptic depolarization produced by intercellular K(+) accumulation cooperates with neurotransmitter exocytosis in sustaining afferent transmission arising from Type I hair cells. While vesicular transmission together with the low Rm of Type I hair cells appears best suited for signaling fast head movements, depolarization produced by intercellular K(+) accumulation could enhance signal transmission during slow head movements
Precision medicine: a new era for inner ear diseases
No full text: The inner ear is the organ responsible for hearing and balance. Inner ear dysfunction can be the result of infection, trauma, ototoxic drugs, genetic mutation or predisposition. Often, like for Ménière disease, the cause is unknown. Due to the complex access to the inner ear as a fluid-filled cavity within the temporal bone of the skull, effective diagnosis of inner ear pathologies and targeted drug delivery pose significant challenges. Samples of inner ear fluids can only be collected during surgery because the available procedures damage the tiny and fragile structures of the inner ear. Concerning drug administration, the final dose, kinetics, and targets cannot be controlled. Overcoming these limitations is crucial for successful inner ear precision medicine. Recently, notable advancements in microneedle technologies offer the potential for safe sampling of inner ear fluids and local treatment. Ultrasharp microneedles can reach the inner ear fluids with minimal damage to the organ, collect μl amounts of perilymph, and deliver therapeutic agents in loco. This review highlights the potential of ultrasharp microneedles, combined with nano vectors and gene therapy, to effectively treat inner ear diseases of different etiology on an individual basis. Though further research is necessary to translate these innovative approaches into clinical practice, these technologies may represent a true breakthrough in the clinical approach to inner ear diseases, ushering in a new era of personalized medicine
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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