Distinct prefrontal projection activity and transcriptional state conversely orchestrate social competition and hierarchy.

Social animals compete for limited resources, resulting in a social hierarchy. Although different neuronal subpopulations in the medial prefrontal cortex (mPFC), which has been mechanistically implicated in social dominance behavior, encode distinct social competition behaviors, their identities and associated molecular underpinnings have not yet been identified. In this study, we found that mPFC neurons projecting to the nucleus accumbens (mPFC-NAc) encode social winning behavior, whereas mPFC neurons projecting to the ventral tegmental area (mPFC-VTA) encode social losing behavior. High-throughput single-cell transcriptomic analysis and projection-specific genetic manipulation revealed that the expression level of POU domain, class 3, transcription factor 1 (Pou3f1) in mPFC-VTA neurons controls social hierarchy. Optogenetic activation of mPFC-VTA neurons increases Pou3f1 expression and lowers social rank. Together, these data demonstrate that discrete activity and gene expression in separate mPFC projections oppositely orchestrate social competition and hierarchy.

Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System.

Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.

Parts per trillion detection of Ni(II) ions by nanoparticle-enhanced surface plasmon resonance.

This paper demonstrates the development of a novel nanoparticle-enhanced surface plasmon resonance (SPR) sensing platform for the selective and sensitive in situ detection of nickel(II) ions at concentrations as low as 50 parts per trillion (211 pM). An enhancement in selectivity was achieved by designing a surface sandwich assay involving two different ligands each selective toward nickel(II) ions, namely, N-[5-(3'-maleimidopropylamido)-1-carboxypentyl]iminodiacetic acid (NTA) and polyhistidine. Maleimido-modified NTA was first immobilized on an alkanedithiol-modified gold thin film, followed by the sequential adsorption of Ni(II) ions. Next, polyhistidine-functionalized quasispherical gold nanoparticles, designed to enhance the SPR sensitivity, were specifically adsorbed onto surface Ni(II)-NTA complexes. This process was monitored by real-time SPR. The ability to detect Ni(II) ions as low as 50 parts per trillion (ppt) is a remarkable improvement compared to other optical and colorimetric techniques utilizing nanoparticles and is comparable to what can be achieved by state-of-the-art inductively coupled plasma mass spectrometry (ICP-MS). The improved selectivity for Ni(II) ions by the sandwich assay approach was confirmed by comparing measurements involving other divalent cations such as Zn(II), Pb(II), and Cu(II), some of which individually possess binding affinities toward either the NTA or histidine moieties.

Highly sensitive electrochemical detection of proteins using aptamer-coated gold nanoparticles and surface enzyme reactions.

A novel electrochemical detection methodology is described for the femtomolar detection of proteins which utilizes both DNA aptamer-functionalized nanoparticles and a surface enzymatic reaction. Immunoglobulin E (IgE) was used as a model protein biomarker, which possesses two distinct epitopes for antibody (anti-IgE) and DNA aptamer binding. A surface sandwich assay format was utilized involving the specific adsorption of IgE onto a gold electrode surface that was pre-modified with a monolayer of aptamer-nanoparticle conjugates followed by the specific interaction of alkaline phosphatase (ALP) conjugated anti-IgE. To clearly demonstrate the signal enhancement associated with nanoparticle use, anodic current measurements of the ALP catalyzed oxidation of the enzyme substrate 4-aminophenylphosphate (APP) were also compared with electrode surfaces upon which the aptamer was directly attached. The detection of an unlabelled protein at concentrations as low as 5 fM is a significant improvement compared to conventional electrochemical-based immunoassay approaches and provides a foundation for the practical use and incorporation of nanoparticle-enhanced detection into electrochemical biosensing technologies.