Biology subjects

Arsenault, J.

Publications and source records attributed to Arsenault, J..

5 recordsLinked to original sources

bioRxiv2025

Metaplastic priming enables non-ionotropic NMDA receptor-mediated synaptic depotentiation in the hippocampus

The reversal of learning-induced synaptic potentiation through depotentiation is thought to underlie forgetting and can be influenced by prior synaptic activity. Here, we evaluated how such metaplastic alterations manifest at the synaptic level. In hippocampal slices obtained from male and female mice, we artificially induced long-term potentiation (LTP) using either a temporally spaced or compressed stimulation pattern. Using a combination of electrophysiology and protein quantification approaches, we found divergent molecular pathways recruited during depotentiation of spaced and compressed LTP. Depotentiation of both forms of LTP required glutamatergic activation of the NMDA receptor (NMDAR). However, only depotentiation of spaced LTP required ionotropic NMDAR signaling, while ion flux-independent, or non-ionotropic, NMDAR signaling was necessary and sufficient for depotentiation of compressed LTP. Downstream of NMDAR signaling, AMPA receptor phosphorylation was also differentially modified during depotentiation of spaced and compressed LTP. Finally, we found that spaced but not compressed depotentiation required synaptic Arc. Together, our results reveal that the temporal pattern of prior LTP induction exerts a metaplastic influence on the molecular pathways recruited during the induction and expression of depotentiation. Our findings have important implications for the regulation of both physiological and pathological forgetting. Significance statementSynaptic depotentiation, the reversal of learning-associated synaptic potentiation, is an important mechanism of forgetting. This study uncovers how prior synaptic activity modifies the molecular mechanisms underlying depotentiation in the hippocampus in a metaplastic manner. We reveal that the mechanisms of NMDA-receptor depotentiation depend on the temporal spacing of long-term potentiation (LTP) induction. Specifically, we show that non-ionotropic NMDA receptor signaling is necessary and sufficient for the depotentiation of LTP induced using temporally compressed but not spaced patterned activity. Further, depotentiation of spaced and compressed LTP are associated with distinct downstream signaling pathways and AMPA receptor phosphorylation states during depotentiation. Our results illuminate fundamental mechanisms that govern plasticity associated with forgetting, with implications for memory preservation in disease states.

neuroscience↗

bioRxiv2024

Disease-linked mutations dysregulate neuronal condensate physical properties, composition, and RNA translation

Local RNA translation is essential for development. In neurons, deficient local translation linked with mutations in scaffold proteins results in dysregulated dendrite and dendritic spine growth. However, mechanisms by which these proteins control translation and how disease-linked mutations induce aberrant translation were unclear. We use biochemical reconstitution and neuronal assays to show that mutations to the neuronal condensate scaffold shank2 cause physical hardening and altered composition of condensates; a key RNA translation-modulator FMRP is excluded from mutant condensates. Functionally, shank2 condensates repress translation while condensates composed of shank2 with intrinsically disordered region-localized missense mutations promote translation. These results demonstrate that disease-linked dysregulation of condensate physical properties and composition is an underlying mechanism of aberrant RNA translation often observed in disease. One Sentence SummaryDisease-linked missense mutations in the postsynaptic density scaffold protein shank2 dysregulate phase separated biomolecular condensate physical properties and composition resulting in aberrant RNA translation.

biophysics↗

bioRxiv2023

Chronic pain mediated changes in the appetitive value of affective touch in mice

The existence of skin-to-brain circuits for rewarding gentle touch highlight its critical nature across species. However, this gentle affective touch is not always appetitive and can produce aversion or negative affect in disorders such as chronic pain. Sensory neurons expressing the protein MrgprB4 detect gentle stroking in mice and their activation of these neurons known to be positively reinforcing. Here we assess whether activation of channelrhodopsin (ChR2) expressing MrgprB4 afferents signal positively valenced tactile information and whether this is altered in models of chronic pain. We further interrogate how this this sensory information is reflected in the downstream circuits recruited. Optogenetic activation of MrgprB4 lineage afferents was found to be appetitive in control and capsaicin sensitized mice but not nerve injured mice, indicating that the appetitive value is diminished in neuropathic pain. Remarkably, this appetitive value was partially recovered in male nerve injured mice by treatment with the analgesic gabapentin. These behavioral changes were also accompanied by different patterns of neuronal activity throughout the brain, including altered activation of sites that receive direct projections from the spinal cord between sham and nerve injured mice. Together, these findings highlight the plastic nature of these affective tactile circuits under pathological conditions.

neuroscience↗

bioRxiv2023

A data-driven evaluation of Arabidopsis-centric research and the model species concept

The selection of Arabidopsis as a model organism played a pivotal role in advancing genomic science, firmly establishing the cornerstone of today s plant molecular biology. Competing frameworks to select an agricultural- or ecological-based model species, or to decentralize plant science and study a multitude of diverse species, were selected against in favor of building core knowledge in a species that would facilitate genome-enabled research that could assumedly be transferred to other plants. Here, we examine the ability of models based on Arabidopsis gene expression data to predict tissue identity in other flowering plant species. Comparing different machine learning algorithms, models trained and tested on Arabidopsis data achieved near perfect precision and recall values using the K-Nearest Neighbor method, whereas when tissue identity is predicted across the flowering plants using models trained on Arabidopsis data, precision values range from 0.69 to 0.74 and recall from 0.54 to 0.64, depending on the algorithm used. Below-ground tissue is more predictable than other tissue types, and the ability to predict tissue identity is not correlated with phylogenetic distance from Arabidopsis. This suggests that gene expression signatures rather than marker genes are more valuable to create models for tissue and cell type prediction in plants. Our data-driven results highlight that, in hindsight, the assertion that knowledge from Arabidopsis is translatable to other plants is not always true. Considering the current landscape of abundant sequencing data and computational resources, it may be prudent to reevaluate the scientific emphasis on Arabidopsis and to prioritize the exploration of plant diversity.

plant biology↗

bioRxiv2021

Mitochondrial ATP Synthase Subunit d, a Component of the Peripheral Stalk, is Essential for Growth and Heat Stress Tolerance in Arabidopsis thaliana.

As rapid changes in climate threaten global crop yields, an understanding of plant heat stress tolerance is increasingly relevant. Heat stress tolerance involves the coordinated action of many cellular processes and is particularly energy demanding. We acquired a knockout mutant and generated knockdown lines in Arabidopsis thaliana of the d subunit of mitochondrial ATP synthase (gene name: ATPQ, AT3G52300, referred to hereafter as ATPd), a subunit of the peripheral stalk, and used these to investigate the phenotypic significance of this subunit in normal growth and heat stress tolerance. Homozygous knockout mutants for ATPd could not be obtained due to gametophytic defects, while heterozygotes possess no visible phenotype. Therefore, we used RNAi to create knockdown plant lines for further studies. Proteomic analysis and blue native gels revealed that ATPd downregulation impairs only subunits of the mitochondrial ATP synthase (complex V of the electron transport chain). Knockdown plants were more sensitive to heat stress, had abnormal leaf morphology, and were severely slow growing compared to wild type. These results indicate that ATPd plays a crucial role in proper function of the mitochondrial ATP synthase holoenzyme, which, when reduced, leads to wide-ranging defects in energy-demanding cellular processes. In knockdown plants, more hydrogen peroxide accumulated and mitochondrial dysfunction stimulon (MDS) genes were activated. These data establish the essential structural role of ATPd and provide new information about complex V assembly and quality control, as well as support the importance of mitochondrial respiration in normal plant growth and heat stress tolerance. SIGNIFICANCE STATEMENTThe energy converter, mitochondrial ATP synthase, is critical for all organisms, but the functional importance of ATP synthase subunit d remains largely unknown in plants. We demonstrate the contributions of subunit d to plant growth, development, and heat stress tolerance, as well as to ATP synthase stability, ROS signaling and mitochondrial dysfunction regulation.

plant biology↗