Biology subjects

Meunier, S.

Publications and source records attributed to Meunier, S..

4 recordsLinked to original sources

bioRxiv2024

Emergence of Pre-movement Beta Activity with Stable Sensorimotor Predictions to Facilitate Motor Adjustments

Adaptive behavior enables flexible responses to environmental changes. This process is particularly crucial when transitioning between environments with different features, relying on the progressive formation of expectations based on prior experience. In humans, beta oscillations are central to adaptive behavior. Yet, the brain mechanisms underlying the detection of environmental changes, and the iterative update needed to progressively improve behavioral performance remain elusive. Here, we reveal that beta activity emerges in a cerebello-cortical network two seconds before action initiation, as the features of a new environment become known and behavioral outcomes become more predictable. Within this period, the cerebellum and parietal cortex drive prefrontal activity to form expectations. Using a single-trial approach, we establish that beta bursts before action initiation predict performance in the upcoming trial based on previous outcomes. These findings uncover a novel anticipatory mechanism that reflects predictive processes critical for stabilizing performance and adapting to environmental changes.

neuroscience↗

bioRxiv2024

TNFR2 blockade promotes anti-tumoral immune response in PDAC by targeting activated Treg and reducing T cell exhaustion

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, highly resistant to standard chemotherapy and immunotherapy. Regulatory T cells (Tregs) expressing TNF receptor 2 (TNFR2) contribute to immunosuppression in PDAC. Treg infiltration correlates with poor survival and tumor progression in PDAC patients. We hypothesized that TNFR2 inhibition using a blocking monoclonal antibody (mAb) could shift the Treg-effector T cell balance in PDAC, thus enhancing anti-tumoral responses. MethodTo support this hypothesis, we first described TNFR2 expression in a cohort of 24 PDAC patients from publicly available single-cell analysis data. In orthotopic and immunocompetent mouse models of PDAC, we also described the immune environment of PDAC after immune cell sorting and single-cell analysis. The modifications of the immune environment before and after anti-TNFR2 mAb treatment were evaluated as well as effect on tumor progression. ResultsPDAC patients exhibited elevated TNFR2 expression in Treg, myeloid cells and endothelial cells but low level in ductal cells. By flow cytometry and single cell RNAseq analysis, we identified two Treg populations in orthotopic mouse models: resting and activated Tregs. The anti-TNFR2 mAb selectively targeted activated tumor-infiltrating Tregs, reducing T cell exhaustion markers in CD8+ T cells. However, anti-TNFR2 treatment alone had limited efficacy in activating CD8+ T cells and only slightly reduced the tumor growth. The combination of the anti-TNFR2 mAb with agonistic anti-CD40 mAbs promoted stronger T cell activation, tumor growth inhibition, and improved survival and immunological memory in PDAC-bearing mice. ConclusionOur data suggest that combining a CD40 agonist with a TNFR2 antagonist represents a promising therapeutic strategy for PDAC patients.

immunology↗

bioRxiv2019

A wave of hematopoietic stem cell-derived T/ILC-restricted progenitors initiates thymopoiesis and shapes the embryonic thymus architecture.

Multiple waves of hematopoietic progenitors with distinct lineage potentials are differentially regulated in time and space. We show that the first thymic seeding progenitors comprise a unique population of bipotent cells that generate lymphoid tissue inducer and invariant V{gamma}5+ T cells. Both populations are of embryonic origin and induce the maturation of medullary thymic epithelial cells. Indeed, temporal depletion of the first wave of thymocytes results in a five-fold reduction of mature medullary thymic epithelial cells, after birth. We further show that these progenitors are of hematopoietic stem cell, and not, of yolk sac origin, despite the temporal overlap between the onset of lymphopoiesis and the transient expression of lymphoid transcripts in yolk sac precursors, that does not impact their strict erythro-myeloid potential. Our work highlights the relevance of the developmental timing on the emergence of different lymphoid subsets required for the establishment of a functionally diverse immune system.

immunology↗

bioRxiv2017

Behavioural Outcomes Of Adult Female Offspring Following Maternal Stress And Perinatal Fluoxetine Exposure

Depression, anxiety, and stress are common in pregnant women. One of the primary pharmacological treatments for anxiety and depression is the antidepressant fluoxetine (Flx). Maternal stress, depression, and Flx exposure are known to effect neurodevelopment of the offspring, however, their combined effects have been scarcely studied, especially in female offspring. The present study investigated the combined effects of maternal stress during pregnancy and perinatal exposure to Flx on the behaviour of female mice as adults. METHODS: Mouse dams were exposed to either chronic unpredictable stress (embryonic (E) day 7 to E18), or FLX (E15-postnatal day 12), or a combination of stress and FLX or left untreated. At two months of age, the female offspring went through a comprehensive behavioural test battery. RESULTS: Maternal stress led to increased activity and alterations of prepulse inhibition in the adult female offspring. Maternal treatment with Flx had a potentially beneficial effect on spatial memory. The combination of prenatal stress and perinatal Flx exposure did not interact in their effects. These results suggest that gestational Flx exposure may have a limited negative impact on female offspring.

neuroscience↗