1,720,969 research outputs found
Retina-attached slice recording reveals light-triggered tonic GABA signaling in suprachiasmatic nucleus
No full text© 2021, The Author(s).Light is a powerful external cue modulating the biological rhythm of internal clock neurons in the suprachiasmatic nucleus (SCN). GABA signaling in SCN is critically involved in this process. Both phasic and tonic modes of GABA signaling exist in SCN. Of the two modes, the tonic mode of GABA signaling has been implicated in light-mediated synchrony of SCN neurons. However, modulatory effects of external light on tonic GABA signalling are yet to be explored. Here, we systematically characterized electrophysiological properties of the clock neurons and determined the spatio-temporal profiles of tonic GABA current. Based on the whole-cell patch-clamp recordings from 76 SCN neurons, the cells with large tonic GABA current (>15 pA) were more frequently found in dorsal SCN. Moreover, tonic GABA current in SCN was highly correlated with the frequency of spontaneous inhibitory postsynaptic current (sIPSC), raising a possibility that tonic GABA current is due to spill-over from synaptic release. Interestingly, tonic GABA current was inversely correlated with slice-to-patch time interval, suggesting a critical role of retinal light exposure in intact brain for an induction of tonic GABA current in SCN. To test this possibility, we obtained meticulously prepared retina-attached SCN slices and successfully recorded tonic and phasic GABA signaling in SCN neurons. For the first time, we observed an early-onset, long-lasting tonic GABA current, followed by a slow-onset, short-lasting increase in the phasic GABA frequency, upon direct light-illumination of the attached retina. This result provides the first evidence that external light cue can directly trigger both tonic and phasic GABA signaling in SCN cell. In conclusion, we propose tonic GABA as the key mediator of external light in SCN.11Nsciescopu
Dopamine-induced astrocytic Ca(2+) signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
No full textDopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D(1)-like or D(2)-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca(2+) signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D(1)R, or D(1)R–D(2)R heteromer to modulate astrocytic Ca(2+) signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca(2+) signaling pathway switches during development: MAO-B is the major player at a young age (5–6 weeks), whereas DA receptors (DARs) are responsible for the adult period (8–12 weeks). DA-mediated Ca(2+) response in the adult period was decreased by either D(1)R or D(2)R blockers, which are primarily known for cyclic AMP signaling (G(s) and G(i) pathway, respectively), suggesting that this Ca(2+) response might be mediated through G(q) pathway by D(1)R–D(2)R heterodimer. Moreover, DAR-mediated Ca(2+) response was not blocked by TTX, implying that this response is not a secondary response caused by neuronal activation. Our study proposes an age-specific molecular target of DA-induced astrocytic Ca(2+) signaling: MAO-B in young mice and DAR in adult mice
A Deafness Associated Protein TMEM43 Interacts with KCNK3 (TASK-1) Two-pore Domain K+ (K2P) Channel in the Cochlea
No full textThe TMEM43 has been studied in human diseases such as arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) and auditory neuropathy spectrum disorder (ANSD). In the heart, the p.(Ser358Leu) mutation has been shown to alter intercalated disc protein function and disturb beating rhythms. In the cochlea, the p.(Arg372Ter) mutation has been shown to disrupt connexin-linked function in glia-like supporting cells (GLSs), which maintain inner ear homeostasis for hearing. The TMEM43-p.(Arg372Ter) mutant knock-in mice displayed a significantly reduced passive conductance current in the cochlear GLSs, raising a possibility that TMEM43 is essential for mediating the passive conductance current in GLSs. In the brain, the two-pore-domain potassium (K2P) channels are generally known as the "leak channels" to mediate background conductance current, raising another possibility that K2P channels might contribute to the passive conductance current in GLSs. However, the possible association between TMEM43 and K2P channels has not been investigated yet. In this study, we examined whether TMEM43 physically interacts with one of the K2P channels in the cochlea, KCNK3 (TASK-1). Utilizing co-immunoprecipitation (IP) assay and Duolink proximity ligation assay (PLA), we revealed that TMEM43 and TASK-1 proteins could directly interact. Genetic modifications further delineated that the intracellular loop domain of TMEM43 is responsible for TASK-1 binding. In the end, gene-silencing of Task-1 resulted in significantly reduced passive conductance current in GLSs. Together, our findings demonstrate that TMEM43 and TASK-1 form a protein-protein interaction in the cochlea and provide the possibility that TASK-1 is a potential contributor to the passive conductance current in GLSs.11Nsciescopuskc
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
Excitation-inhibition imbalance leads to alteration of neuronal coherence and neurovascular coupling under acute stress
No full text© 2020 Han et al. A single stressful event can cause morphologic and functional changes in neurons and even malfunction of vascular systems, which can lead to acute stress disorder or post-traumatic stress disorder. However, there is a lack of evidence regarding how acute stress impacts neuronal activity, the concurrent vascular response, and the relationship between these two factors, which is defined as neurovascular coupling. Here, using in vivo two-photon imaging, we found that NMDA-evoked calcium transients of excitatory neurons were impaired and that vasodilation of penetrating arterioles was concomitantly disrupted in acutely stressed male mice. Furthermore, acute stress altered the relationship between excitatory neuronal calcium coherence and vascular responses. By measuring NMDA-evoked excitatory and inhibitory neuronal calcium activity in acute brain slices, we confirmed that neuronal coherence both between excitatory neurons and between excitatory and inhibitory neurons was reduced by acute stress but restored by blockade of glucocorticoid receptor signaling. Furthermore, the ratio of sEPSCs to sIPSCs was altered by acute stress, suggesting that the excitation-inhibition balance was disrupted by acute stress. In summary, in vivo, ex vivo, and whole-cell recording studies demonstrate that acute stress modifies excitatory-inhibitory neuronal coherence, disrupts the excitation-inhibition balance, and causes consequent neurovascular coupling changes, providing critical insights into the neural mechanism of stress-induced disorders11sciescopu
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
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