Arc/Arg3.1 mRNA Global Expression Patterns Elicited by Memory Recall in Cerebral Cortex Differ for Remote Versus Recent Spatial Memories

The neocortex plays a critical role in the gradual formation and storage of remote declarative memories. Because the circuitry mechanisms of systems-level consolidation are not well understood, the precise cortical sites for memory storage and the nature of enduring memory correlates (mnemonic plasticity) are largely unknown. Detailed maps of neuronal activity underlying recent and remote memory recall highlight brain regions that participate in systems consolidation and constitute putative storage sites, and thus may facilitate detection of mnemonic plasticity. To localize cortical regions involved in the recall of a spatial memory task, we trained rats in a water-maze and then mapped mRNA expression patterns of a neuronal activity marker Arc/Arg3.1 (Arc) upon recall of recent (24 h after training) or remote (1 month after training) memories and compared them with swimming and naive controls. Arc gene expression was significantly more robust 24 h after training compared to 1 month after training. Arc expression diminished in the parietal, cingulate and visual areas, but select segments in the prefrontal, retrosplenial, somatosensory and motor cortical showed similar robust increases in the Arc expression. When Arc expression was compared across select segments of sensory, motor and associative regions within recent and remote memory groups, the overall magnitude and cortical laminar patterns of task-specific Arc expression were similar (stereotypical). Arc mRNA fractions expressed in the upper cortical layers (2/3, 4) increased after both recent and remote recall, while layer 6 fractions decreased only after the recent recall. The data suggest that robust recall of remote memory requires an overall smaller increase in neuronal activity within fewer cortical segments. This activity trend highlights the difficulty in detecting the storage sites and plasticity underlying remote memory. Application of the Arc maps may ameliorate this difficulty

BHLHE40 regulates the T-cell effector function required for tumor microenvironment remodeling and immune checkpoint therapy efficacy

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential ICT-induced immune cell remodeling. The BHLHE40-dependent gene expression changes indicated dysregulated metabolism, NF-κB signaling, and IFNγ response within certain subpopulations of CD4+ and CD8+ T cells. Intratumoral CD4+ and CD8+ T cells from BHLHE40-deficient mice exhibited higher expression of the inhibitory receptor gene Tigit and displayed alterations in expression of genes encoding chemokines/chemokine receptors and granzyme family members. Mice lacking BHLHE40 had reduced ICT-driven IFNγ production by CD4+ and CD8+ T cells and defects in ICT-induced remodeling of macrophages from a CX3CR1+CD206+ subpopulation to an iNOS+ subpopulation that is typically observed during effective ICT. Although both anti-PD-1 and anti-CTLA-4 ICT in BHLHE40-deficient mice led to the same outcome-tumor outgrowth-several BHLHE40-dependent alterations were specific to the ICT that was used. Our results reveal a crucial role for BHLHE40 in effective ICT and suggest that BHLHE40 may be a predictive or prognostic biomarker for ICT efficacy and a potential therapeutic target

Entangled plasmon generation in nonlinear spaser systems

The work is focused on the investigation of features of quantum dynamics for localized plasmons in spaser systems consisting of metal nanoparticles (NP) and semiconductor quantum dots (QDs). The non-classical plasmon states generation in a three-particle spaser system with nonlinear plasmon-exciton interaction is predicted

The method of surface plasmon-polariton pulses generation via cooperative effects in a waveguide spaser

Cooperative effects arising under conditions of a 0-D model for a dense ensemble of semiconductor quantum dots located in a dielectric layer near a flat metal surface are considered. The threshold conditions of the effect are determined and the values of the complex refractive index of the dielectric are chosen, which make it possible to increase the efficiency of the formation of surface plasmon-polariton (SPP) pulses

The method of surface plasmon-polariton pulses generation via cooperative effects in a waveguide spaser

Cooperative effects arising under conditions of a 0-D model for a dense ensemble of semiconductor quantum dots located in a dielectric layer near a flat metal surface are considered. The threshold conditions of the effect are determined and the values of the complex refractive index of the dielectric are chosen, which make it possible to increase the efficiency of the formation of surface plasmon-polariton (SPP) pulses

Entangled plasmon generation in nonlinear spaser systems

The work is focused on the investigation of features of quantum dynamics for localized plasmons in spaser systems consisting of metal nanoparticles (NP) and semiconductor quantum dots (QDs). The non-classical plasmon states generation in a three-particle spaser system with nonlinear plasmon-exciton interaction is predicted