Biology subjects

Fortin, N.

Publications and source records attributed to Fortin, N..

8 recordsLinked to original sources

bioRxiv2026

Multimodal transcriptomics and calcium imaging reveal a novel subset of polymodal nociceptors expressing the interleukin 1 receptor in mice

We previously established that sensory neurons in the mouse dorsal root ganglia (DRG) express a functional receptor for the proinflammatory cytokine interleukin (IL)-1. We also demonstrated that deletion of the IL-1 receptor type 1 gene, Il1r1, in TRPV1-expressing (+) neurons prevented pain in models of chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis and osteoarthritis. Here, we found a marked sex difference in the abundance of IL-1R1+ neurons, which represented approximately 10% of all DRG neurons in females but only 5% in males. However, male mice exhibited stronger, longer-lasting mechanical hypersensitivity than females after IL-1{beta} injection into the cerebrospinal fluid. In vivo calcium imaging revealed that IL-1{beta}- responsive DRG neurons responded to cutaneous mechanical and capsaicin stimulation. By integrating spatial transcriptomics with single-cell RNA sequencing (scRNA-Seq), we identified a gene signature uniquely marking IL-1R1+ neurons, including genes such as Ada, Cysltr2, Gpr139, Htr1a, Htr1f, Il31ra, Nppb, Npy2r, Nts, P2rx2, Pde4c, and Sst, with Ada and Sst validated at the protein level. Omics analysis revealed that IL-1R1+ DRG neurons form a subset of non-peptidergic type 3 (NP3) sensory neurons, which are linked to inflammatory pain and itch. However, Il1r1 deletion did not affect itch responses to serotonin, histamine, or chloroquine, and these mediators failed to induce calcium activity in IL-1{beta}-responsive DRG neurons. Finally, scRNA-seq identified several genes upregulated in NP3 neurons after IL-1{beta} injection, including Alkal2, Bdnf, and Lcn2, associated with chronic inflammatory pain. Thus, our study unveils novel markers for IL-1R1+ nociceptors and reaffirms their selective role in inflammatory pain.

neuroscience↗

bioRxiv2026

Immunoglobulins are rapidly internalized by neurons after CNS injury and cleared through lysosomal degradation

Spinal cord injury (SCI) causes hemorrhage and blood-spinal cord barrier disruption, allowing blood-derived molecules to infiltrate the parenchyma. While immunoglobulins (Ig) are abundant plasma proteins, their distribution and cellular targets within the injured spinal cord remain poorly defined. Here, we show that circulating non-autoimmune immunoglobulins rapidly infiltrate the spinal cord after injury in mice and disseminate beyond the lesion core. IgG, IgM, and IgA accumulate within the parenchyma early post-injury, with IgG displaying the widest spatial distribution, reaching distant spinal segments within hours. Neurons are the predominant cell type internalizing immunoglobulins in the gray matter, whereas astrocytes exhibit moderate uptake in white matter. Intra-cisterna magna administration of fluorescent serum-derived IgG reveals that neurons and astrocytes internalize IgG under physiological conditions, independently of Fc receptor engagement. Although the neonatal Fc receptor (FcRn) has minimal impact on CNS IgG recycling, its genetic deletion significantly improves locomotor recovery after SCI. Both in vitro and in vivo, neurons clear IgG through lysosomal degradation. Following SCI, inhibition of lysosomal proteases with the clinically approved drug E64d increases CNS IgG retention without compromising locomotor recovery. These findings establish neurons as key targets of circulating immunoglobulins after CNS injury and reveal IgG uptake and clearance pathways that may be leveraged to improve therapeutic performance of monoclonal antibody treatments.

neuroscience↗

bioRxiv2026

Decision analysis in support of proactive planning for chronic wasting disease in Vermont, USA

Chronic wasting disease (CWD), a fatal, transmissible disease in white-tailed deer (Odocoileus virginianus) and related species, is spreading across North America but has not yet been detected in Vermont, United States (U.S.). The Vermont Department of Fish and Wildlife, along with partner agencies, wants to develop a proactive prevention and response plan in anticipation of the eventual detection of the disease. Between September 2023 and September 2025, staff from the U.S. Geological Survey and the University of Vermont facilitated a structured decision-making (SDM) process with seven State and Federal agencies that have jurisdiction over some aspect of CWD management in Vermont. The aim of this process was to generate and evaluate alternative response plans against a range of long-term objectives important to the agencies. To aid in the evaluation of the alternatives, we developed a linked set of models for white-tailed deer population and disease dynamics, hunter participation and health, forest health, economic consequences, and agricultural opportunities related to the actions being contemplated as part of the response plan. We evaluated over 256 different permutations of management actions and used multi-criteria decision analysis, a branch of decision analysis designed to help decision makers navigate tradeoffs among competing objectives, to summarize the performance of those alternative strategies against the desired outcomes. Proactive actions, those designed to slow the arrival of CWD to Vermont, were moderately effective, but the most important proactive action was surveillance to detect the disease early after arrival, which triggered response actions after detection. With the insights generated by the SDM process and the results of the analyses, the participating agencies were able to identify a preferred strategy and outline the elements of a proactive response plan. This report describes the SDM process, the technical details of the modeling work, and the results of the analyses.

ecology↗

bioRxiv2025

Deciphering the dynamics of Cyanobacteria-Phage in a natural lake: Insights from a decade-long investigation

Phages - viruses that infect bacteria - are often seen as key players in bacterial community dynamics and the ecosystem services those communities support. However, much of our understanding of phage-bacteria interactions comes from in vitro studies, which provide limited insights into how these interactions occur in natural environments. In this study, we used cyanobacterial blooms as a model microbial community to evaluate the potential role of phages in driving cyanobacterial populations. These blooms are characterized by massive and usually rapid accumulation of cyanobacterial biomass and occur worldwide, threatening aquatic systems. The frequency and intensity of cyanobacterial blooms are increasing over time, likely due to human activities, and, until now, the role of predators like phages has remained unclear. We used a deep amplicon sequencing approach targeting the g20 capsid gene to profile the cyanophage community in eutrophic Lake Champlain over time, comparing their dynamics and diversity with bacterial communities and examining their associations. We evaluated whether phages simply followed bacterial dynamics, with limited impact on bacterial composition, or instead whether they played an active role in drving bacterial community structure. We found that phages exhibited similar dynamics to their potential bacterial hosts and shared environmental niches. However, we also observed strong differences specific to the phage community, such as inter-annual variation and an increase in Shannon diversity over time. Phage-bacteria and phage-cyanobacteria co-variance uncovered potential interactions that resulted in strongly modular networks. However, while the network structure remained modular, the composition of the modules differed significantly between environmental and temporal conditions. Lastly, viral phylogeny partially explained phage-bacteria co-variance, but only for a small proportion of bacterial ASVs. Our results indicate that phage-bacterial interactions are partly genetically structured and vary within modules across environmental conditions.

ecology↗

bioRxiv2020

Single-colony sequencing reveals phylosymbiosis, co-phylogeny, and horizontal gene transfer between the cyanobacterium Microcystis and its microbiome

Cyanobacteria from the genus Microcystis can form large mucilaginous colonies with attached heterotrophic bacteria - their microbiome. However, the nature of the relationship between Microcystis and its microbiome remains unclear. Is it a long-term, evolutionarily stable association? Which partners benefit? Here we report the genomic diversity of 109 individual Microcystis colonies - including cyanobacteria and associated bacterial genomes - isolated in situ and without culture from Lake Champlain, Canada and Pampulha Reservoir, Brazil. We found 14 distinct Microcystis genotypes from Canada, of which only two have been previously reported, and four genotypes specific to Brazil. Microcystis genetic diversity was much greater between than within colonies, consistent with colony growth by clonal expansion rather than aggregation of Microcystis cells. We also identified 72 bacterial species in the microbiome. Each Microcystis genotype had a distinct microbiome composition, and more closely-related genotypes had more similar microbiomes. This pattern of phylosymbiosis could be explained by co-phylogeny in two out of the nine most prevalent associated bacterial genera, Roseomonas and Rhodobacter, suggesting long-term evolutionary associations. Roseomonas and Rhodobacter genomes encode functions which could complement the metabolic repertoire of Microcystis, such as cobalamin and carotenoid biosynthesis, and nitrogen fixation. In contrast, other colony-associated bacteria showed weaker signals of co-phylogeny, but stronger evidence of horizontal gene transfer with Microcystis. These observations suggest that acquired genes are more likely to be retained in both partners (Microcystis and members of its microbiome) when they are loosely associated, whereas one gene copy is sufficient when the association is physically tight and evolutionarily long-lasting.

microbiology↗

bioRxiv2020

CA1 20-40 Hz oscillatory dynamics reflect trial-specific information processing supporting nonspatial sequence memory

The hippocampus is known to play a critical role in processing information about temporal context. However, it remains unclear how hippocampal oscillations are involved, and how their functional organization is influenced by connectivity gradients. We examined local field potential activity in CA1 as rats performed a complex odor sequence memory task. We find that odor sequence processing epochs were characterized by increased power in the 4-8 Hz and 20-40 Hz range, with 20-40 Hz oscillations showing a power gradient increasing toward proximal CA1. Running epochs were characterized by increased power in the 8-12 Hz range and across higher frequency ranges (>24 Hz), with power gradients increasing toward proximal and distal CA1, respectively. Importantly, 20-40 Hz power increased with knowledge of the sequence and carried trial-type-specific information. These results suggest that 20-40 Hz oscillations are associated with trial-specific processing of nonspatial information critical for order memory judgments.

neuroscience↗

bioRxiv2019

Coherence of Microcystis species revealed through population genomics

Microcystis is a genus of freshwater cyanobacteria which causes harmful blooms in ecosystems worldwide. Some Microcystis strains produce harmful toxins such as microcystin, impacting drinking water quality. Microcystis colony morphology, rather than genetic similarity, is often used to classify Microcystis into morphospecies. However, colony morphology is a plastic trait which can change depending on environmental and laboratory culture conditions, and is thus an inadequate criterion for species delineation. Furthermore, Microcystis populations are thought to disperse globally and constitute a homogeneous gene pool. However, this assertion is based on relatively incomplete characterization of Microcystis genomic diversity. To better understand these issues, we performed a population genomic analysis of 33 newly sequenced genomes (of which 19 were resequenced to check for mutation in culture) mainly from Canada and Brazil. We identified eight Microcystis clusters of genomic similarity, only four of which correspond to named morphospecies and monophyletic groups. Notably, M. aeruginosa is paraphyletic, distributed across four genomic clusters, suggesting it is not a coherent species. Most monophyletic groups are specific to a unique geographic location, suggesting biogeographic structure over relatively short evolutionary time scales. Higher homologous recombination rates within than between clusters further suggest that monophyletic groups might adhere to a Biological Species-like concept, in which barriers to gene flow maintain species distinctness. However, certain genes - including some involved in microcystin and micropeptin biosynthesis - are recombined between monophyletic groups in the same geographic location, suggesting local adaptation. Together, our results show the importance of using genomic criteria for Microcystis species delimitation and suggest the existence of locally adapted lineages and genes. ImportanceThe genus Microcystis is responsible for harmful and often toxic cyanobacterial blooms across the world, yet it is unclear how and if the genus should be divided into ecologically and genomically distinct species. To resolve the controversy and uncertainty surrounding Microcystis species, we performed a population genomic analysis of Microcystis genome from public databases, along with new isolates from Canada and Brazil. We inferred that significant genetic substructure exists within Microcystis, with several species being maintained by barriers to gene flow. Thus, Microcystis appears to be among a growing number of bacteria that adhere to a Biological Species-like Concept (BSC). Barriers to gene flow are permeable, however, and we find evidence for relatively frequent cross-species horizontal gene transfer (HGT) of genes that may be involved in local adaptation. Distinct clades of Microcystis (putative species) tend to have distinct profiles of toxin biosynthesis genes, and yet toxin genes are also subject to cross-species HGT and local adaptation. Our results thus pave the way for more informed classification, monitoring and understanding of harmful Microcystis blooms.

microbiology↗

bioRxiv2017

Niche separation increases with genetic distance among bloom-forming cyanobacteria

Bacterial communities are composed of distinct groups of potentially interacting lineages, each thought to occupy a distinct ecological niche. It remains unclear, however, how quickly niche preference evolves and whether more closely related lineages are more likely to share ecological niches. We addressed these questions by following the dynamics of two bloom-forming cyanobacterial genera over an 8-year time-course in Lake Champlain, Canada, using 16S amplicon sequencing and measurements of several environmental parameters. The two genera, Microcystis (M) and Dolichospermum (D), are frequently observed simultaneously during bloom events and thus have partially overlapping niches. However, the extent of their niche overlap is debated, and it is also unclear to what extent niche partitioning occurs among strains within each genus. To identify strains within each genus, we applied minimum entropy decomposition (MED) to 16S rRNA gene sequences. We confirmed that at a genus level, M and D have different preferences for nitrogen and phosphorus concentrations. Within each genus, we also identified strains differentially associated with temperature, precipitation, and concentrations of nutrients and toxins. In general, niche similarity between strains (as measured by co-occurrence over time) declined with genetic distance. This pattern is consistent with habitat filtering - in which closely-related taxa are ecologically similar, and therefore tend to co-occur under similar environmental conditions. In contrast with this general pattern, similarity in certain niche dimensions (notably particulate nitrogen and phosphorus) did not decline linearly with genetic distance, and instead showed a complex polynomial relationship. This observation suggests the importance of processes other than habitat filtering - such as competition between closely-related taxa, or convergent trait evolution in distantly-related taxa - in shaping particular traits in microbial communities.

ecology↗