The hM4Di receptor-based chemogenetic DREADD system has been widely used to suppress neuronal activities, which has contributed substantially to the identification of behavior-associated neuronal circuitries including those in the striatum. One major mechanism by which hM4Di receptor activation suppresses neuronal activity is that the activation reduces membrane excitability, which is thought to be mediated by the opening of GIRK channels. However, previous studies have suggested that GIRK channels are barely expressed in the striatum, which naturally raises the question whether the hM4Di receptor activation-induced reduction in membrane excitability found in striatal medium spiny neurons (MSNs, which constitute 95–98% of the striatal neuronal population) is truly mediated by the endogenous GIRK channels in such scarcity. This study aims to answer this question by applying a GIRK channel-selective blocker, tertiapin-Q (TPNQ), to striatal MSNs. This study first verified that application of clozapine (CZP), an hM4Di receptor agonist, to MSNs expressing the hM4Di receptors hyperpolarized the cell membrane, and reduced membrane excitability and input resistance. This study next revealed that TPNQ post-treatment completely canceled the above CZP-induced electrophysiological effects and that TPNQ pretreatment mostly prevented further expression of the above CZP-induced electrophysiological effects. In addition, confocal microscopy imaging also revealed significant above-background GIRK1 immunofluorescence signals in striatal MSNs. These data suggest that the TPNQ-sensitive GIRK channels, despite being expressed at low levels, are likely the major mediator downstream of hM4Di receptor activation to reduce membrane excitability in striatal MSNs. These results imply that the notion held by scientists in the field that GIRK channels are absent in the striatum or their expression level is not significant enough to exert any function might be oversimplified or incorrect.
The high quality of polished end face of photonic crystal fiber has a significant effect on coupling efficiency when photonic crystal fiber is used to couple with other optical devices. In order to obtain the smooth surface of the photonic crystal fiber, the end face polishing process of the photonic crystal fiber is analyzed using the finite element method in this article. Because there are many small air holes in the cladding of photonic crystal fiber, it needs better processing technology than that of ordinary fiber. The formation mechanism of cracks and the effects of cutting depth and grit tip radius on the processing results are researched, and this process is simplified as a single grit cutting a single hole wall and the cutting depth of grit with different diameters under certain lapping force is obtained by theoretical analysis. The simulation results show that finite element method can effectively simulate the end face lapping process of photonic crystal fiber, and that in the polishing process of photonic crystal fiber, the edge of hole wall is prone to the collapse area which is distributed along the circumference; cutting force and collapse area increase with the cutting depth and grit tip radius. For no collapse area generation, the maximum cutting depth of this photonic crystal fiber is less than the critical cutting depth of brittle plastic transition of ordinary fiber.
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