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Depression is a common mood disorder characterized by a range of clinical symptoms, including prolonged low mood and diminished interest. Although many clinical and animal studies have provided significant insights into the pathophysiology of depression, current treatment strategies are not sufficient to manage this disorder. It has been suggested that connexin (Cx)-based hemichannels are candidates for depression intervention by modifying the state of neuroinflammation. In this study, we investigated the antidepressant-like effect of a recently discovered selective Cx hemichannel inhibitor, a small organic molecule called D4. We first showed that D4 reduced hemichannel activity following systemic inflammation after LPS injections. Next, we found that D4 treatment prevented LPS-induced inflammatory response and depressive-like behaviors. These behavioral effects were accompanied by reduced astrocytic activation and hemichannel activity in depressive-like mice induced by repeated low-dose LPS challenges. D4 treatment also reverses depressive-like symptoms in mice subjected to chronic restraint stress (CRS). To test whether D4 broadly affected neural activity, we measured c-Fos expression in depression-related brain regions and found a reduction in c-Fos+ cells in different brain regions. D4 significantly normalized CRS-induced hypoactivation in several brain regions, including the hippocampus, entorhinal cortex, and lateral septum. Together, these results indicate that blocking Cx hemichannels using D4 can normalize neuronal activity and reduce depressive-like symptoms in mice by reducing neuroinflammation. Our work provides evidence of the antidepressant-like effect of D4 and supports glial Cx hemichannels as potential therapeutic targets for depression. [ABSTRACT FROM AUTHOR]

Information represented by principal neurons in anterior piriform cortex (APC) is regulated by local, recurrent excitation and inhibition, but the circuit mechanisms remain elusive. Two types of layer 2 (L2) principal neurons, semilunar (SL), and superficial pyramidal (SP) cells, are parallel output channels, and the control of their activity gates the output of APC. Here, we examined the hypothesis that recurrent inhibition differentially regulates SL and SP cells. Patterned optogenetic stimulation revealed that the strength of recurrent inhibition is target‐ and layer‐specific: L1 > L3 for SL cells, but L3 > L1 for SP cells. This target‐ and layer‐specific inhibition was largely attributable to the parvalbumin (PV), but not somatostatin, interneurons. Intriguingly, olfactory experience selectively modulated the PV to SP microcircuit while maintaining the overall target and laminar specificity of inhibition. Together, these results indicate the importance of target‐specific inhibitory wiring for odor processing, implicating these mechanisms in gating the output of piriform cortex. [ABSTRACT FROM AUTHOR]

Improving the dispersion of metal nanoparticles and suppressing metal aggregation have long been the keys to constructing efficient metal-loaded catalysts. Herein, catalysts of cobalt (Co) supported on nitrogen (N)-doped carbon were prepared by a simple hydrothermal method using folic acid (FA) as the carbon source. Surprisingly, hydrazine hydrate not only facilitated the loading of metal Co, but also regulated the morphology of the catalyst, promoted the uniform distribution of metal Co, and effectively improved the catalytic hydrogenation activity of the catalyst. It was found that the catalyst mediated with 10 mL hydrazine hydrate and pyrolyzed at 900 °C exhibited the best catalytic performance (99.6% conversion of quinoline and 98.0% selectivity for 1,2,3,4-tetrahydroquinoline). In addition, it exhibited satisfying adaptability for diverse substrates. This study can provide great theoretical significance and practical guidance for the preparation of Co–N–C catalysts. [ABSTRACT FROM AUTHOR]