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Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown ofGrm2resulted in decreased b/c-Raf kinases and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused byGrm2knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENTMetabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We providedin vivoandin vitroevidence to show that GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality. more...

Early sensory experiences interact with genes to shape precise neural circuits during development. This process is vital for proper brain function in adulthood. Neurological dysfunctions caused by environmental alterations and/or genetic mutation may share the same molecular or cellular mechanisms. Here, we show that early life bilateral whisker trimming (BWT) subsequently affects social discrimination in adult male mice. Enhanced activation of the hippocampal dorsal CA3 (dCA3) in BWT mice was observed during social preference tests. Optogenetic activation of dCA3 in naive mice impaired social discrimination, whereas chemogenetic silencing of dCA3 rescued social discrimination deficit in BWT mice. Hippocampal oxytocin (OXT) is reduced after whisker trimming. Neonatal intraventricular compensation of OXT relieved dCA3 over-activation and prevented social dysfunction. Neonatal knockdown of OXT receptor in dCA3 mimics the effects of BWT, and cannot be rescued by OXT treatment. Social behavior deficits in a fragile X syndrome mouse model (Fmr1 KO mice) could also be recovered by early life OXT treatment, through negating dCA3 over-activation. Here, a possible avenue to prevent social dysfunction is uncovered. more...

During postnatal development, sensory experience shapes the organization and function of cortical circuits. Previous studies focusing on experience-dependent plasticity of neurons have revealed a variety of mechanisms underlying cortical circuit rewiring. Emerging evidence shows that astrocytes play important roles in shaping cortical circuits through extensive interactions with different types of neurons and other glia cells. However, it remains unclear how astrocytes respond to sensory experience during postnatal development. In the present study, we profiled the maturation of astrocytes in the primary visual cortex (V1) at different postnatal stages. We then investigated the anatomical and physiological changes of astrocytes in V1 induced by multiple types of visual experience within 4 postnatal weeks. Compared with monocular deprivation during the critical period, binocular deprivation showed stronger impact on reactive astrocytes in V1. Moreover, long-term binocular deprivation significantly reduced the density of reactive astrocytes in layer 2/3 of V1 while strengthening gap junction couplings between astrocytes at the same time. Therefore, our data demonstrated that cortical astrocytes could undergo homeostatic plasticity in response to long-term changes of sensory inputs. The plasticity of astrocytes may interact with the plasticity of neurons to cooperatively shape cortical circuit refinement during postnatal development. more...

It is well known that premixed and non-premixed flamelets coexist in the combustion system, especially for multiphase combustion (Luo et al., 2011; Bai et al., 2016). In this work, a multi-regime combustion model for partially premixed multiphase combustion (2PMC) is developed in the framework of large eddy simulation (LES). In this model, the multi-regime combustion mode is decomposed into two pure combustion regimes (i.e. premixed and non-premixed) through combustion regime indicator. Different combustion models are chosen for different combustion regimes. For example, for premixed combustion regime, the flamelet generated manifold (FGM) tabulation method in combination with the artificially thickened flame (ATF) approach is used. For non-premixed combustion regime, on the other hand, the thermo-chemical quantities will be extracted from the non-premixed chemtable generated by the flamelet/progress variable (FPV) approach. The proposed multi-regime flamelet model is then extended to adapt to the pulverized coal combustion (PCC) and applied to a laboratory-scale pulverized coal jet flame. The simulation results show that the percentage of the volume-weighted premixed combustion regime of this studied flame is up to 18%. Quantitative comparisons between the experimental data and the numerical results with the present multi-regime flamelet model, the FPV model, and the Eddy Break Up (EBU) model shows that the proposed multi-regime flamelet model has several advantages. It performs better than the FPV model in the regions where premixed combustion mode prevails and also much better than the EBU model in species concentration prediction. more...

Plant species composition and vegetation coverage are critical indicators in vegetation disturbance and restoration, but their correlations are dynamic and complex under human disturbance. Inadequate attention has been paid to the correlations between species composition and vegetation coverage associated with vegetation disturbance on plateaus. We analyze the origin of species, chorological spectra, life-forms and dominant species in the Napahai wetland of Yunnan Province, China. The correlations between species composition and vegetation coverage associated with human disturbance were then investigated by hierarchical partitioning and regression analysis. A total of 71 plant species belonging to 47 genera and 24 families were identified. Our results revealed that the plant composition of the Napahai Plateau vegetation was relatively monotonous, with the three dominant chorological types consisting of 68.4–100.0% of all genera. The wetlands studied have suffered from significant changes in species compos... more...