Astrocyte responds to neuronal activity with calcium waves and modulates synaptic transmission through the release of gliotransmitters. However, little is known about the direct effect of gliotransmitters on the excitability of neuronal networks beyond synapses. Here we show that selective stimulation of astrocytes expressing channelrhodopsin-2 in the CA1 area specifically increases the firing frequency of CCK-positive but not parvalbumin-positive interneurons and decreases the firing rate of pyramidal neurons, phenomena mimicked by exogenously applied ATP. Further evidences indicate that ATP-induced increase and decrease of excitability are caused, respectively, by P2Y1 receptor-mediated inhibition of a two-pore domain potassium channel and A1 receptor-mediated opening of a G-protein-coupled inwardly rectifying potassium channel. Moreover, the activation of ChR2-expressing astrocytes reduces the power of kainate-induced hippocampal ex vivo gamma oscillation. Thus, through distinct receptor subtypes coupled with different K+ channels, astrocyte-derived ATP differentially modulates the excitability of different types of neurons and efficiently controls the activity of neuronal network.

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Microglia are the resident immune cells in the CNS and play diverse roles in the maintenance of CNS homeostasis. Recent studies have shown that microglia continually survey the CNS microenvironment and scavenge cell debris and aberrant proteins by phagocytosis and pinocytosis, and that reactive microglia are capable to present antigens to T cells and initiate immune responses. However, how microglia process the endocytosed contents and evoke an immune response remain unclear. Here we report that a size-dependent selective transport of small soluble contents from the pinosomal lumen into lysosomes is critical for the antigen processing in microglia. Using fluorescent probes and water-soluble magnetic nanobeads of defined sizes, we showed in cultured rodent microglia, and in a cell-free reconstructed system that pinocytosed proteins become degraded immediately following pinocytosis and the resulting peptides are selectively delivered to major histocompatibility complex class II (MHC-II) containing lysosomes, whereas undegraded proteins are retained in the pinosomal lumen. This early size-based sorting of pinosomal contents relied on the formation of transient tunnel between pinosomes and lysosomes in a Rab7-and dynamin II-dependent manner, which allowed the small contents to pass through but restricted large ones. Inhibition of the size-based sorting markedly reduced proliferation and cytokine release of cocultured CD4 ϩ T cells, indicating that the size-based sorting is required for efficient antigen presentation by microglial cells. Together, these findings reveal a novel early sorting mechanism for pinosomal luminal contents in microglial cells, which may explain how microglia efficiently process protein antigens and evoke an immune response.

The failure of locked segment-type slopes is often affected by rainfall, earthquake, and other external loads. Rainfall scours the slope and weakens the mechanical properties of rock-soil mass. At the same time, rainfall infiltrates into cracks of slope rock mass. Under the action of in situ stress, hydraulic fracturing leads to the development and expansion of rock cracks, which increases the risk of slope instability. Under seismic force, the slope will be subjected to large horizontal inertial force, resulting in slope instability. In this paper, a self-developed loading device was used to simulate the external loads such as rainfall and earthquake, and the model tests are carried out to study the evolution mechanism of landslide with retaining wall locked segment. Three-dimensional laser scanner, microearth pressure sensors, and high-definition camera are applied for the high-precision monitoring of slope shape, deformation, and stress. Test results show that the retaining wall locked segment has an important control effect on landslide stability. The characteristics of deformation evolution and stress response of landslide with retaining wall locked segment are analyzed and studied by changing the slope shape, earth pressure, and the displacement cloud map. The evolutionary process of landslide with retaining wall locked segment is summarized. Experimental results reveal that as the landslide with retaining wall locked segment is at failure, the upper part of the landslide thrusts and slides and the retaining wall produces a locking effect; the middle part extrudes and uplifts, which is accompanied with shallow sliding; and compression-shear fracture of the locked segment leads to the landslide failure.