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Low-voltage-activated T-type Ca(2+) channels are widely expressed in various types of neurons. Once deinactivated by hyperpolarization, T-type channels are ready to be activated by a small depolarization near the resting membrane potential and, therefore, are optimal for regulating the excitability and electroresponsiveness of neurons under physiological conditions near resting states. Ca(2+) influx through T-type channels engenders low-threshold Ca(2+) spikes, which in turn trigger a burst of a

Biophysical cues, such as topography, and electrical cues can provide external stimulation for the promotion of stem cell neurogenesis. Here, we demonstrate an electroconductive surface nanotopography for enhancing neuronal differentiation and the functional maturation of human neural stem cells (hNSCs). The electroconductive nanopatterned substrates were prepared by depositing a thin layer of titanium (Ti) with nanograting topographies (150 to 300 nm groove/ridge, the thickness of the groove -

Two firing modes of thalamocortical (TC) neurons, tonic and burst firings, are thought to reflect the divergent states of sensory signal transmission from the thalamus to the cortex. However, the behavioral consequences of changes in the thalamic firing between the two modes have not been well demonstrated. Moreover, although the firing modes of TC neurons are known to be affected by corticothalamic inputs via thalamic metabotropic glutamate receptor type 1 (mGluR1)-phospholipase C beta4 (PLCbet

We investigated the transport of neuronal mitochondria using superlocalized near-fields with plasmonic nanohole arrays (PNAs). Compared to traditional imaging techniques, PNAs create a massive array of superlocalized light beams and allow 3D mitochondrial dynamics to be sampled and extracted almost in real time. In this work, mitochondrial fluorescence excited by the PNAs was captured by an optical microscope using dual objective lenses, which produced superlocalized dynamics while minimizing li

Absence seizures are characterized by cortical spike-wave discharges (SWDs) on electroencephalography, often accompanied by a shift in the firing pattern of thalamocortical (TC) neurons from tonic to burst firing driven by T-type Ca(2+) currents. We recently demonstrated that the phospholipase C beta4 (PLCbeta4) pathway tunes the firing mode of TC neurons via the simultaneous regulation of T- and L-type Ca(2+) currents, which prompted us to investigate the contribution of TC firing modes to abse

A reduction in the strong immunosuppressive activity of FK506 (<b>1</b>) is essential for developing this compound as an antifungal agent. Seven new FK506 analogues modified at both the FK506-binding protein 12- and the calcineurin-binding regions were biosynthesized. 9-DeoxoFK520 (<b>7</b>) exhibited a >900-fold reduction in the <i>in vitro</i> immunosuppressive activity but maintained significant antifungal activity, indicating that the C-9 and C-21 positions are critical for separation of imm

Ryanodine receptors (RyRs) are highly conductive intracellular Ca(2+) release channels which are widely expressed in the CNS. They rapidly increase the intracellular Ca(2+) concentrations in neuronal cells in response to Ca(2+) influx through voltage-gated Ca(2+) channels. A previous study reported that RyRs were expressed in thalamocortical (TC) neurons, but their physiological function has remained elusive. Here, we show that the activation of RyRs in TC neurons in mice decreases their tonic f