Biology subjects

Marron, A.

Publications and source records attributed to Marron, A..

4 recordsLinked to original sources

bioRxiv2025

Oxytocin enhances excitability and potentiates synaptic transmission in dentate gyrus granule cells

The dentate gyrus is the principal gateway for information into the hippocampus. The dentate gyrus transforms input from the entorhinal cortex into sparse, selective representations that support memory formation. Oxytocin is a key neuromodulator of social behavior and supports social memory through its actions in hippocampal area CA2. However, whether oxytocin also modulates the dentate gyrus (DG), a source of major excitatory input to CA2, remains unclear. We performed whole-cell recordings to test if oxytocin modulated the excitability of mouse dentate gyrus granule cells. We found that bath application of the oxytocin receptor agonist Thy4, Gly7-oxytocin (TGOT) increased DG granule cell excitability by depolarizing the resting membrane potential, increasing input resistance, and hyperpolarizing action potential threshold. In addition to increasing postsynaptic excitability, we found that TGOT decreased the paired-pulse ratio of perforant path to granule cell synapses and also increased the frequency, without an effect on amplitude, of miniature EPSCs suggesting that TGOT increased the probability of glutamate release. Notably, long-term potentiation induced by theta-burst pairing occluded the effect of TGOT on synaptic strength suggesting that oxytocin and long-term potentiation may converge on common downstream mechanisms. Our results revealed a previously uncharacterized role for oxytocin in regulating the relay of information between the entorhinal cortex and dentate gyrus. This suggests a potential mechanism through which oxytocin shapes hippocampal processing of socially relevant stimuli. Significance StatementOxytocin is essential for social memory and acts prominently within hippocampal area CA2, yet its influence on the dentate gyrus, a major excitatory input of CA2, has remained unclear. We demonstrate that oxytocin modulates dentate gyrus granule cell signaling by enhancing intrinsic excitability and strengthening perforant path synaptic transmission via increased presynaptic release probability. We further show that long-term potentiation occludes these synaptic effects suggesting convergence between oxytocin signaling and activity-dependent plasticity. These findings identify a previously unrecognized role for oxytocin in shaping dentate gyrus processing, broadening our understanding of how neuromodulatory signals influence hippocampal circuits involved in social information processing. Key pointsO_LIOxytocin increases dentate gyrus granule cell excitability by depolarizing resting membrane potential, increasing input resistance and hyperpolarizing action potential threshold. C_LIO_LIOxytocin enhances perforant path synaptic transmission by increasing presynaptic glutamate release probability. C_LIO_LILong-term potentiation occludes the synaptic effects of oxytocin, suggesting overlap in downstream mechanisms. C_LI

neuroscience↗

bioRxiv2025

Immune System Alterations in Depression across Baseline and Flu Vaccine Challenge

There are multiple reports of elevated inflammation in patients with major depression. It is, however, unclear whether these reported perturbations in immune functions in depression affect the general functionality of the peripheral immune system. Here, using single-cell RNAsequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) extracted from blood samples collected prior to a flu vaccination administration/immunization (at baseline), we found downregulated T cell and B-cell-associated gene expression repertoire coupled with a selectively upregulated plasmablast, CD14 classical monocytes, and natural killer (NK) proliferating cell-associated gene expression in 9 depressed patients (6 females) compared to 5 healthy controls (5 females), as well as in association with depression ratings. Our cell type proportion analysis revealed shifts in immune cell populations, specifically reduced numbers of CD4+ T and CD8+ T proliferating cells, plasmablasts, and NK cells in individuals with depression compared with controls. In contrast, we found increased numbers of CD14 classical and CD16 monocytes as well as doublet cells in depressed individuals compared with controls. Although our baseline and flu vaccine challenge did not show marked differences in peripheral immune markers measured by a multiplex cytokine assay, our results suggest impaired innate and adaptive immune responses at the transcriptomic and cellular population levels in depressed patients.

immunology↗

bioRxiv2022

An optimised transformation protocol for Anthoceros agrestis and three more hornwort species

Land plants comprise two large monophyletic lineages, the vascular plants and the bryophytes, which diverged from their most recent common ancestor approximately 480 million years ago. Of the three lineages of bryophytes, only the mosses and the liverworts are systematically investigated, while the hornworts are understudied. Despite their importance for understanding fundamental questions of land plant evolution, they only recently became amenable to experimental investigation, with Anthoceros agrestis being developed as a hornwort model system. Availability of a high quality genome assembly and a recently developed genetic transformation technique makes A. agrestis an attractive model species for hornworts. Here we describe an updated and optimised transformation protocol for A. agrestis which can be successfully used to genetically modify one more strain of A. agrestis and three more hornwort species, Anthoceros punctatus, Leiosporoceros dussi and Phaeoceros carolinianus. The new transformation method is less laborious, faster and results in the generation of greatly increased numbers of transformants compared to the previous method. We have also developed a new selection marker for transformation. Finally, we report the development of a set of different cellular localisation signal peptides for hornworts providing new tools to better understand hornwort cell biology.

plant biology↗

bioRxiv2022

Transgenerational effects of alcohol on intoxication sensitivity in Caenorhabditis elegans

Alcohol abuse and dependence have a substantial heritable component. Although the genome has been considered the sole vehicle of heritable phenotypes, recent studies suggest that drug or alcohol exposure may induce alterations in gene expression that are transmitted across generations. Still, the transgenerational impact of alcohol use (and abuse) remains largely unexplored in part because multigenerational studies using rodent models present challenges for time, sample size, and genetic heterogeneity. Here, we took advantage of the extremely short generation time, large broods, and clonal form of reproduction of the nematode Caenorhabditis elegans. We developed a model of preconception parental alcohol exposure to test alterations in behavioral responses to acute alcohol treatment (intoxication) in subsequent F1, F2 and F3 generations. We found that a chronic alcohol-treatment paradigm in the parental generation resulted in alcohol-naive F3 progeny displaying moderate resistance to intoxication. To compare the treatment duration and timing on this transgenerational effect, we repeated the study using an intermittent treatment paradigm. We found that intermittent treatment resulted in alcohol-naive F3 progeny displaying moderate hypersensitivity to intoxication. Further study of this phenomena using this new C. elegans model may yield mechanistic insights into how transgenerational effects may occur in other animals.

genetics↗