33 research outputs found

    The amount of astrocytic GABA positively correlates with the degree of tonic inhibition in hippocampal CA1 and cerebellum

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    A tonic form of synaptic inhibition occurs in discrete regions of the central nervous system and has an important role in controlling neuronal excitability. Recently, we reported that GABA present in astrocyte is the major source of tonic inhibition in cerebellum and that GABA is released through Bestrophin-1 channel by direct permeation. In this study, we screened for the presence of astrocytic GABA in various brain regions such as hippocampus, thalamus, hypothalamus and cerebellum using immunohistochemistry. We found that astrocytic GABA was present in the regions that were reported to show tonic inhibition. Because the existence of tonic inhibition in hippocampal CA1 is somewhat controversial, we compared the amount of astrocytic GABA and tonic inhibition between the hippocampal CA1 pyramidal cell layer and the cerebellar granule cell layer. Unlike cerebellar glial cells, hippocampal astrocytes did not contain GABA. The tonic inhibition was also much lower in the pyramidal neurons of hippocampal CA1 compared to the granule cells of cerebellum. Nevertheless, most of the hippocampal astrocytes expressed Bestrophin-1 channel. These data indicate that the absence of astrocytic GABA results in a low level of tonic inhibition in hippocampal CA1 region

    Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K2P) and voltage-gated (Kv1.1 and Kv1.2) potassium channels

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    <p>Abstract</p> <p>Background</p> <p>Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons.</p> <p>Findings</p> <p>When IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K<sup>+ </sup>channels, K<sub>v</sub>1.1 and K<sub>v</sub>1.2 (voltage-gated K<sup>+ </sup>channels) and TREK1 and TRAAK (K<sub>2P </sub>channels). IQ effectively reduced the currents mediated by both K<sup>+ </sup>channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K<sub>v</sub>1.1 and K<sub>v</sub>1.2.</p> <p>Conclusions</p> <p>Our results demonstrate that IQ blocks the voltage-gated K<sup>+ </sup>channels to increase AP duration and K<sub>2P </sub>channels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus.</p

    Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons

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    Abstract Background GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s. Results Whole-cell patch recordings were performed to evaluate the effects of briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the junction between layer 6 and the underlying white matter (L6/WM stimulation). Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization in the center of the column-shaped region. However, both prior to or 30s after stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed that GABA induced depolarization is due to an increase in [Cl-]i after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABAA receptors agonist, was applied right after stimulation while monitoring the intracellular Ca2+ concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca2+]i in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca2+ signal showed a column-shaped distribution along the stimulation site. Conclusion These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons

    First-time comparison between NO2 vertical columns from GEMS and Pandora measurements

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    The Geostationary Environmental Monitoring Spectrometer (GEMS) is a UV&ndash;visible spectrometer onboard the GEO-KOMPSAT-2B satellite launched into geostationary orbit in February 2020. To evaluate GEMS NO2 column data, comparison was carried out using NO2 vertical column density (VCD) measured using direct-sunlight observations by the Pandora spectrometer system at four sites in Seosan, South Korea, during November 2020 to January 2021. Correlation coefficients between GEMS and Pandora NO2 data at four sites ranged from 0.35 to 0.48, with root mean square errors (RMSEs) from 4.7 &times; 1015 molec. cm-2 to 5.5 &times; 1015 molec. cm-2 for cloud fraction (CF) &lt; 0.7. Higher correlation coefficients of 0.62&ndash;0.78 with lower RMSEs from 3.3 &times; 1015 molec. cm-2 to 4.3 &times; 1015 molec. cm-2 were found with CF &lt; 0.3, indicating the higher sensitivity of GEMS to atmospheric NO2 in less-cloudy conditions. Overall, GEMS NO2 column data tend to be lower than those of Pandora due to differences in representative spatial coverage, with a large negative bias under high-CF conditions. With correction for horizontal representativeness in Pandora measurement coverage, the correlation coefficients range from 0.69 to 0.81 with RMSEs from 3.2 &times; 1015 molec. cm-2 to 4.9 &times; 1015 molec. cm-2 were achieved for CF &lt; 0.3, showing the better correlation with the correction than that without the correction.</p

    First-time comparison between NO2 vertical columns from Geostationary Environmental Monitoring Spectrometer (GEMS) and Pandora measurements

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    The Geostationary Environmental Monitoring Spectrometer (GEMS) is a UV-visible (UV-Vis) spectrometer on board the GEO-KOMPSAT-2B (Geostationary Korea Multi-Purpose Satellite 2B) satellite launched into a geostationary orbit in February 2020. To evaluate the GEMS NO2 total column data, a comparison was carried out using the NO2 vertical column density (VCD) that measured direct sunlight using the Pandora spectrometer system at four sites in Seosan, South Korea, from November 2020 to January 2021. Correlation coefficients between GEMS and Pandora NO2 data at four sites ranged from 0.35 to 0.48, with root mean square errors (RMSEs) from 4.7×1015 to 5.5×1015 molec. cm−2 for a cloud fraction (CF) &lt;0.7. Higher correlation coefficients of 0.62–0.78 with lower RMSEs from 3.3×1015 to 5.0×1015 molec. cm−2 were found with CF &lt;0.3, indicating the higher sensitivity of GEMS to atmospheric NO2 in less cloudy conditions. Overall, the GEMS NO2 total column data tended to be lower than the Pandora data, owing to differences in the representative spatial coverage, with a large negative bias under high CF conditions. With a correction for horizontal representativeness in the Pandora measurement coverage, correlation coefficients ranging from 0.69 to 0.81, with RMSEs from 3.2×1015 to 4.9×1015 molec. cm−2, were achieved for CF &lt;0.3, showing a better correlation with the correction than without the correction.</p

    New Era of Air Quality Monitoring from Space: Geostationary Environment Monitoring Spectrometer (GEMS)

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    GEMS will monitor air quality over Asia at unprecedented spatial and temporal resolution from GEO for the first time, providing column measurements of aerosol, ozone and their precursors (nitrogen dioxide, sulfur dioxide and formaldehyde). Geostationary Environment Monitoring Spectrometer (GEMS) is scheduled for launch in late 2019 - early 2020 to monitor Air Quality (AQ) at an unprecedented spatial and temporal resolution from a Geostationary Earth Orbit (GEO) for the first time. With the development of UV-visible spectrometers at sub-nm spectral resolution and sophisticated retrieval algorithms, estimates of the column amounts of atmospheric pollutants (O3, NO2, SO2, HCHO, CHOCHO and aerosols) can be obtained. To date, all the UV-visible satellite missions monitoring air quality have been in Low Earth orbit (LEO), allowing one to two observations per day. With UV-visible instruments on GEO platforms, the diurnal variations of these pollutants can now be determined. Details of the GEMS mission are presented, including instrumentation, scientific algorithms, predicted performance, and applications for air quality forecasts through data assimilation. GEMS will be onboard the GEO-KOMPSAT-2 satellite series, which also hosts the Advanced Meteorological Imager (AMI) and Geostationary Ocean Color Imager (GOCI)-2. These three instruments will provide synergistic science products to better understand air quality, meteorology, the long-range transport of air pollutants, emission source distributions, and chemical processes. Faster sampling rates at higher spatial resolution will increase the probability of finding cloud-free pixels, leading to more observations of aerosols and trace gases than is possible from LEO. GEMS will be joined by NASA&apos;s TEMPO and ESA&apos;s Sentinel-4 to form a GEO AQ satellite constellation in early 2020s, coordinated by the Committee on Earth Observation Satellites (CEOS)
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