Author Correction: Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior.

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Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior.

Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair. Moreover, knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed by chronic administration of the selective serotonin reuptake inhibitor fluoxetine. To determine whether habenular cholinergic signaling is associated with regulation of dopamine neurons in the ventral tegmental area (VTA) and serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic mice expressing the Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5-hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation was recapitulated in the postmortem habenula of suicide victims diagnosed with major depressive disorder (MDD).

Insights into cationic ordering in Re-based double perovskite oxides.

Cationic ordering in Sr2FeReO6 (SFRO) and Sr2CrReO6 (SCRO) is investigated using magnetic property measurement, atomic-scale imaging, and first-principles calculations. We find that the nature of cationic ordering strongly depends on the host oxides, although they have the same crystal symmetry and chemical formula. Firstly, adding Re is effective to enhance the cationic ordering in SFRO, but makes it worse in SCRO. Secondly, the microscopic structure of antisite (AS) defects, associated with the level of cationic ordering, is also distinguishable; the AS defects in SFRO are clustered in the form of an antiphase-boundary-like feature, while they are randomly scattered in SCRO. Interestingly, we observe that the clustered AS defects deteriorate the ferromagnetism more than the scattered defects. Our findings elevate the importance of the AS defect configuration as well as the amount of defects in terms of magnetic property.

Arhgef7 promotes activation of the Hippo pathway core kinase Lats.

The Hippo pathway regulates tissue growth and organ size, and inactivation contributes to cancer. Signals flow through Mst/Lats kinases, which phosphorylate and promote cytoplasmic localization of the transcriptional regulators Yap and Taz to inhibit transcription. Here, we identify the multidomain-containing guanine nucleotide exchange factor (GEF) Arhgef7, or ßPix, as a positive Hippo pathway regulator. We show that ßPix, which localizes to the cytoplasm, binds both Lats and Yap/Taz and thereby promotes Lats-mediated phosphorylation of Yap/Taz in a GEF-independent manner. ßPix is required downstream of both cell density sensing and actin cytoskeletal rearrangements, and we demonstrate that loss of ßPix expression in normal mammary epithelial cells strongly reduces Yap/Taz phosphorylation, promotes nuclear localization and increases target gene expression. Conversely, increased expression of ßPIX in breast cancer cell lines re-couples the Hippo kinase cassette to Yap/Taz, promoting localization of Yap/Taz to the cytoplasm and inhibiting cell migration and proliferation. These studies thus define ßPix as a key component that links the Hippo kinase cassette to Yap/Taz in response to multiple upstream Hippo pathway activators.