Density and distribution patterns of seafloor macrolitter in the eastern Red Sea.

The constant production of plastic and incessant growth of waste pollution continues to alter the marine environment from the coasts and surface waters to the deep sea. The quantification and investigation of macrolitter on the vast seabed of the ocean are challenging tasks that must be undertaken to elucidate the impact of anthropogenic activity on the marine environment and facilitate subsequent implementation of legally binding waste management regulations. In this study, we analyzed >60,000 images collected during 84 dives surveying 62.1 km of seabed in the eastern Red Sea to quantify the abundance and density of seafloor macrolitter. The surveyed depth of the seabed varied between 35 and 2415 m, and litter was observed at depths ranging from 93 to 2415 m. The litter density varied between 0 and 73,798 items km-2, with the mean (± SE) and median densities of 4069 ± 1188 and 1371 items km-2, respectively. Plastic was the main litter category, comprising 46 % of all litter. The density of litter was higher at deeper depths (>1400 m) and increased significantly at distances farther from the shore. The results of this study suggest that maritime traffic and the possible direct litter discharge from vessels are the main anthropogenic sources of seafloor litter in the eastern Red Sea. Thus, we emphasize the urgency of conservation efforts and strict waste regulations to preserve the marine ecosystem of the Red Sea.

Stability in human serum and plasma of the HIV peptide drug candidate CIGB-210 and improved variants.

The peptide CIGB-210 inhibits HIV replication, inducing a rearrangement of vimentin intermediate filaments. The assessment of the in vitro serum and plasma stability of this peptide is important to develop an optimal pharmacological formulation. A half-life of 17.68 ± 0.59 min was calculated for CIGB-210 in human serum by reverse-phase high-performance liquid chromatography (HPLC) and mass spectrometry (MS). Eight metabolites of CIGB-210 were identified with this methodology, all of them lacking the N-terminal moiety. A previously developed CIGB-210 in-house competitive ELISA was used to compare the stability of CIGB-210 derivatives containing either D-amino acids, acetylation at the N-terminus, or both modifications. The half-life of CIGB-210 in serum was five times higher when measured by ELISA than by HPLC/MS, and twice higher in plasma as compared to serum. The substitution of D-asparagine on position 6 doubled the half-life, while D-amino acids on positions 8 and 9 did not improve the stability. The acetylation of the N-terminus resulted in a 24-fold more stable peptide in plasma. The positive effect of N-terminal acetylation on CIGB-210 serum stability was confirmed by the HPLC/MS method, as the half-life of the peptide was not reached after 2 h of incubation, which represents more than a 6.8-fold increase in the half-life with respect to the original peptide.

A generalized numerical model for clonal growth in scleractinian coral colonies.

Coral reefs, vital ecosystems supporting diverse marine life, are primarily shaped by the clonal expansion of coral colonies. Although the principles of coral clonal growth, involving polyp division for spatial extension, are well-understood, numerical modelling efforts are notably scarce in the literature. In this article, we present a parsimonious numerical model based on the cloning of polyps, using five key parameters to simulate a range of coral shapes. The model is agent-based, where each polyp represents an individual. The colony's surface expansion is dictated by the growth mode parameter (s), guiding the preferred growth direction. Varying s facilitates the emulation of diverse coral shapes, including massive, branching, cauliflower, columnar and tabular colonies. Additionally, we introduce a novel approach for self-regulatory branching, inspired by the intricate mesh-like canal system and internode regularity observed in Acropora species. Through a comprehensive sensitivity analysis, we demonstrate the robustness of our model, paving the way for future applications that incorporate environmental factors, such as light and water flow. Coral colonies are known for their high plasticity, and understanding how individual polyps interact with each other and their surroundings to create the reef structure has been a longstanding question in the field. This model offers a powerful framework for studying these interactions, enabling a future implementation of environmental factors and the possibility of identifying the key mechanisms influencing coral colonies' morphogenesis.

Assessing patterns of metazoans in the global ocean using environmental DNA.

Documenting large-scale patterns of animals in the ocean and determining the drivers of these patterns is needed for conservation efforts given the unprecedented rates of change occurring within marine ecosystems. We used existing datasets from two global expeditions, Tara Oceans and Malaspina, that circumnavigated the oceans and sampled down to 4000 m to assess metazoans from environmental DNA (eDNA) extracted from seawater. We describe patterns of taxonomic richness within metazoan phyla and orders based on metabarcoding and infer the relative abundance of phyla using metagenome datasets, and relate these data to environmental variables. Arthropods had the greatest taxonomic richness of metazoan phyla at the surface, while cnidarians had the greatest richness in pelagic zones. Half of the marine metazoan eDNA from metagenome datasets was from arthropods, followed by cnidarians and nematodes. We found that mean surface temperature and primary productivity were positively related to metazoan taxonomic richness. Our findings concur with existing knowledge that temperature and primary productivity are important drivers of taxonomic richness for specific taxa at the ocean's surface, but these correlations are less evident in the deep ocean. Massive sequencing of eDNA can improve understanding of animal distributions, particularly for the deep ocean where sampling is challenging.

Metabolites from Marine Macroorganisms of the Red Sea Acting as Promoters or Inhibitors of Amylin Aggregation.

Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with ß-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation.

A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid ß (Aß)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aß in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential to be a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation): protocol for a multicenter randomized open-label trial of watchful waiting versus antimicrobial therapy for ventilator-associated tracheobronchitis.

BACKGROUND: Ventilator-associated tracheobronchitis is a common condition among invasively ventilated patients in intensive care units, for which the best treatment strategy is currently unknown. We designed the VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation) trial to assess whether a watchful waiting antibiotic treatment strategy is noninferior to routine antibiotic treatment for ventilator-associated tracheobronchitis regarding days free of mechanical ventilation. METHODS: VATICAN is a randomized, controlled, open-label, multicenter noninferiority trial. Patients with suspected ventilator-associated tracheobronchitis without evidence of ventilator-associated pneumonia or hemodynamic instability due to probable infection will be assigned to either a watchful waiting strategy, without antimicrobial administration for ventilator-associated tracheobronchitis and prescription of antimicrobials only in cases of ventilator-associated pneumonia, sepsis or septic shock, or another infectious diagnosis, or to a routine antimicrobial treatment strategy for seven days. The primary outcome will be mechanical ventilation-free days at 28 days, and a key secondary outcome will be ventilator-associated pneumonia-free survival. Through an intention-to-treat framework with a per-protocol sensitivity analysis, the primary outcome analysis will address noninferiority with a 20% margin, which translates to a 1.5 difference in ventilator-free days. Other analyses will follow a superiority analysis framework. CONCLUSION: The VATICAN trial will follow all national and international ethical standards. We aim to publish the trial in a high-visibility general journal and present it at critical care and infectious disease conferences for dissemination. These results will likely be immediately applicable to the bedside upon trial completion and will provide information with a low risk of bias for guideline development.

Shipping traffic through the Arctic Ocean: Spatial distribution, seasonal variation, and its dependence on the sea ice extent.

The reduction in sea ice cover with Arctic warming facilitates shipping through remarkably shorter shipping routes. Automatic identification system (AIS) is a powerful data source to monitor Arctic Ocean shipping. Based on the AIS data from an online platform, we quantified the spatial distribution of shipping through this area, its intensity, and the seasonal variation. Shipping was heterogeneously distributed with power-law exponents that depended on the vessel category. We contextualized the estimated exponents with the analytical distribution of a transit model in one and two dimensions. Fishing vessels had the largest spatial spread, while narrower shipping routes associated with cargo and tanker vessels had a width correlated with the sea ice area. The time evolution of these routes showed extended periods of shipping activity through the year. We used AIS data to quantify recent Arctic shipping, which brings an opportunity for shorter routes, but likely impacting the Arctic ecosystem.

A sedimentary DNA record of the Atacama Trench reveals biodiversity changes in the most productive marine ecosystem.

The hadopelagic environment remains highly understudied due to the inherent difficulties in sampling at these depths. The use of sediment environmental DNA (eDNA) can overcome some of these restrictions as settled and preserved DNA represent an archive of the biological communities. We use sediment eDNA to assess changes in the community within one of the world's most productive open-ocean ecosystems: the Atacama Trench. The ecosystems around the Atacama Trench have been intensively fished and are affected by climate oscillations, but the understanding of potential impacts on the marine community is limited. We sampled five sites using sediment cores at water depths from 2400 to ~8000 m. The chronologies of the sedimentary record were determined using 210Pbex. Environmental DNA was extracted from core slices and metabarcoding was used to identify the eukaryote community using two separate primer pairs for different sections of the 18S rRNA gene (V9 and V7) effectively targeting pelagic taxa. The reconstructed communities were similar among markers and mainly composed of chordates and members of the Chromista kingdom. Alpha diversity was estimated for all sites in intervals of 15 years (from 1842 to 2018), showing a severe drop in biodiversity from 1970 to 1985 that aligns with one of the strongest known El Niño events and extensive fishing efforts during the time. We find a direct impact of sea surface temperature on the community composition over time. Fish and cnidarian read abundance was examined separately to determine whether fishing had a direct impact, but no direct relation was found. These results demonstrate that sediment eDNA can be a valuable emerging tool providing insight in historical perspectives on ecosystem developments. This study constitutes an important step toward an improved understanding of the importance of environmental and anthropogenic drivers in affecting open and deep ocean communities.

Microorganisms Involved in Methylmercury Demethylation and Mercury Reduction are Widely Distributed and Active in the Bathypelagic Deep Ocean Waters.

The ocean's mercury (Hg) content has tripled due to anthropogenic activities, and although the dark ocean (>200 m) has become an important Hg reservoir, concentrations of the toxic and bioaccumulative methylmercury (MeHg) are low and therefore very difficult to measure. As a consequence, the current understanding of the Hg cycle in the deep ocean is severely data-limited, and the factors controlling MeHg, as well as its transformation rates, remain largely unknown. By analyzing 52 globally distributed bathypelagic deep-ocean metagenomes and 26 new metatranscriptomes from the Malaspina Expedition, our study reveals the widespread distribution and expression of bacterial-coding genes merA and merB in the global bathypelagic ocean (∼4000 m depth). These genes, associated with HgII reduction and MeHg demethylation, respectively, are particularly prevalent within the particle-attached fraction. Moreover, our results indicate that water mass age and the organic matter composition shaped the structure of the communities harboring merA and merB genes living in different particle size fractions, their abundance, and their expression levels. Members of the orders Corynebacteriales, Rhodobacterales, Alteromonadales, Oceanospirillales, Moraxellales, and Flavobacteriales were the main taxonomic players containing merA and merB genes in the deep ocean. These findings, together with our previous results of pure culture isolates of the deep bathypelagic ocean possessing the metabolic capacity to degrade MeHg, indicated that both methylmercury demethylation and HgII reduction likely occur in the global dark ocean, the largest biome in the biosphere.

High temperature and solar radiation in the Red Sea enhance the dissolution of crude oil from surface films.

The Red Sea is a hotspot of biodiversity susceptible to oil pollution. Besides, it is one of the warmest seas on the Earth with highly transparent waters. In this study, we estimated the oil dissolution rates under natural sunlight spectra and temperature conditions using coastal oil slicks collected after the 2019 Sabiti oil spill in the Red Sea. Optical analyses revealed the significant interactive effect of sunlight and temperature in enhancing the dissolution of oil into dissolved organic matter (DOM). The highest oil dissolution rate (38.68 g C m-3 d-1) was observed in full-spectrum sunlight. Oil dissolution significantly enhanced total organic carbon (TOC) and polycyclic aromatic hydrocarbons (PAHs) in seawater. High nucleic acid (HNA) bacteria, likely the oil degraders, proliferated from 30 to 70 - 90% after 4 days. The heavier stable carbon isotopic composition of methane (δ13C-CH4) and lighter stable carbon isotopic composition of carbon dioxide (δ13C-CO2) indicate the putative role of bacterial processes in the natural degradation of crude oil. The results indicated that the combined effect of temperature and solar radiation enhanced the biological and photochemical dissolution of oil on the Red Sea surface.

Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

Discernible decline in macroplastic litter inputs to the central eastern Red Sea shoreline during the COVID-19 lockdown.

Plastic debris accumulating on beaches pose a major threat to marine ecosystems. Unexpected events affecting human operations, such as the COVID-19 pandemic, which prompted governments to implement safety measures and restrictions, can serve as an unplanned investigation of anthropogenic pressure on the marine environment. This study aimed to explore deviations in macroplastic delivery rates to the central eastern Red Sea shoreline during three distinct population mobility periods: before, during, and after COVID-19 restrictions, spanning from January 2019 to June 2022. We observed a 50 % reduction in the estimated macroplastic delivery rates during the lockdown, followed by a 25 % increase after restrictions were eased. Seasonal variations in delivery rates were also observed, with higher values during the winter monsoon. Reduced shoreline litter delivery during the pandemic highlights human operations as a cause of macroplastic litter and suggests the potential of temporary measures to reduce plastic pollution in the coastal environment.

The active free-living bathypelagic microbiome is largely dominated by rare surface taxa.

A persistent microbial seed bank is postulated to sustain the marine biosphere, and recent findings show that prokaryotic taxa present in the ocean's surface dominate prokaryotic communities throughout the water column. Yet, environmental conditions exert a tight control on the activity of prokaryotes, and drastic changes in these conditions are known to occur from the surface to deep waters. The simultaneous characterization of the total (DNA) and active (i.e. with potential for protein synthesis, RNA) free-living communities in 13 stations distributed across the tropical and subtropical global ocean allowed us to assess their change in structure and diversity along the water column. We observed that active communities were surprisingly more similar along the vertical gradient than total communities. Looking at the vertical connectivity of the active vs. the total communities, we found that taxa detected in the surface sometimes accounted for more than 75% of the active microbiome of bathypelagic waters (50% on average). These active taxa were generally rare in the surface, representing a small fraction of all the surface taxa. Our findings show that the drastic vertical change in environmental conditions leads to the inactivation and disappearance of a large proportion of surface taxa, but some surface-rare taxa remain active (or with potential for protein synthesis) and dominate the bathypelagic active microbiome.

Systematic review of the uncertainty of coral reef futures under climate change.

Climate change impact syntheses, such as those by the Intergovernmental Panel on Climate Change, consistently assert that limiting global warming to 1.5 °C is unlikely to safeguard most of the world's coral reefs. This prognosis is primarily based on a small subset of available models that apply similar 'excess heat' threshold methodologies. Our systematic review of 79 articles projecting coral reef responses to climate change revealed five main methods. 'Excess heat' models constituted one third (32%) of all studies but attracted a disproportionate share (68%) of citations in the field. Most methods relied on deterministic cause-and-effect rules rather than probabilistic relationships, impeding the field's ability to estimate uncertainty. To synthesize the available projections, we aimed to identify models with comparable outputs. However, divergent choices in model outputs and scenarios limited the analysis to a fraction of available studies. We found substantial discrepancies in the projected impacts, indicating that the subset of articles serving as a basis for climate change syntheses may project more severe consequences than other studies and methodologies. Drawing on insights from other fields, we propose methods to incorporate uncertainty into deterministic modeling approaches and propose a multi-model ensemble approach to generating probabilistic projections for coral reef futures.

Enterobacteria in anaerobic digestion of dairy cattle wastewater: Assessing virulence and resistance for one health security.

Samples from a dairy cattle waste-fed anaerobic digester were collected across seasons to assess sanitary safety for biofertilizer use. Isolated enterobacteria (suggestive of Escherichia coli) were tested for susceptibility to biocides, antimicrobials, and biofilm-forming capability. Results revealed a decrease in total bacteria, coliforms, and enterobacteria in biofertilizer compared to the effluent. Among 488 isolates, 98.12 % exhibited high biofilm formation. Biofertilizer isolates exhibited a similar biofilm formation capability as effluent isolates in summer, but greater propensity in winter. Resistance to biocides and antimicrobials varied, with tetracycline resistance reaching 19 %. Of the isolates, 25 were multidrug-resistant (MDR), with 64 % resistant to three drugs. Positive correlations were observed between MDR and increased biofilm formation capacity in both samples, while there was negative correlation between MDR and increased biocide resistance. A higher number of MDR bacteria were found in biofertilizer compared to the effluent, revealing the persistence of E. coli resistance, posing challenges to food safety and public health.

Marine picoplankton metagenomes and MAGs from eleven vertical profiles obtained by the Malaspina Expedition.

The Ocean microbiome has a crucial role in Earth's biogeochemical cycles. During the last decade, global cruises such as Tara Oceans and the Malaspina Expedition have expanded our understanding of the diversity and genetic repertoire of marine microbes. Nevertheless, there are still knowledge gaps regarding their diversity patterns throughout depth gradients ranging from the surface to the deep ocean. Here we present a dataset of 76 microbial metagenomes (MProfile) of the picoplankton size fraction (0.2-3.0 µm) collected in 11 vertical profiles covering contrasting ocean regions sampled during the Malaspina Expedition circumnavigation (7 depths, from surface to 4,000 m deep). The MProfile dataset produced 1.66 Tbp of raw DNA sequences from which we derived: 17.4 million genes clustered at 95% sequence similarity (M-GeneDB-VP), 2,672 metagenome-assembled genomes (MAGs) of Archaea and Bacteria (Malaspina-VP-MAGs), and over 100,000 viral genomic sequences. This dataset will be a valuable resource for exploring the functional and taxonomic connectivity between the photic and bathypelagic tropical and sub-tropical ocean, while increasing our general knowledge of the Ocean microbiome.

Quantifying mangrove carbon assimilation rates using UAV imagery.

Mangrove forests are recognized as one of the most effective ecosystems for storing carbon. In drylands, mangroves operate at the extremes of environmental gradients and, in many instances, offer one of the few opportunities for vegetation-based sequestering of carbon. Developing accurate and reproducible methods to map carbon assimilation in mangroves not only serves to inform efforts related to natural capital accounting, but can help to motivate their protection and preservation. Remote sensing offers a means to retrieve numerous vegetation traits, many of which can be related to plant biophysical or biochemical responses. The leaf area index (LAI) is routinely employed as a biophysical indicator of health and condition. Here, we apply a linear regression model to UAV-derived multispectral data to retrieve LAI across three mangrove sites located along the coastline of the Red Sea, with estimates producing an R2 of 0.72 when compared against ground-sampled LiCOR LAI-2200C LAI data. To explore the potential of monitoring carbon assimilation within these mangrove stands, the UAV-derived LAI estimates were combined with field-measured net photosynthesis rates from a LiCOR 6400/XT, providing a first estimate of carbon assimilation in dryland mangrove systems of approximately 3000 ton C km-2 yr-1. Overall, these results advance our understanding of carbon assimilation in dryland mangroves and provide a mechanism to quantify the carbon mitigation potential of mangrove reforestation efforts.

Isolation and Bioactivity Evaluation of Sesquiterpenes from an Alcyonarian of the Genus Lemnalia from the Saudi Arabian Red Sea.

Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south-west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three (13, 14 and 28) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non-cancerous cell lines for a number of biological activities, including their cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)-regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N-acetylcysteine, albeit at a 10-fold lower concentration.

The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity.

Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, the efficiency of which depends on inter-individual variation in fear extinction learning, which neurobiological basis is unknown. We characterized a model of extinction learning, whereby fear-conditioned mice were categorized as extinction (EXT)-success or EXT-failure, according to their inherent ability to extinguish fear. In the lateral amygdala, GluN2A-containing NMDAR are required for LTP and stabilization of fear memories, while GluN2B-containing NMDAR are required for LTD and fear extinction. EXT-success mice showed attenuated LTP, strong LTD and higher levels of synaptic GluN2B, while EXT-failure mice showed strong LTP, no LTD and higher levels of synaptic GluN2A. Neurotrophin 3 (NT3) infusion in the lateral amygdala was sufficient to rescue extinction deficits in EXT-failure mice. Mechanistically, activation of tropomyosin receptor kinase C (TrkC) with NT3 in EXT-failure slices attenuated lateral amygdala LTP, in a GluN2B-dependent manner. Conversely, blocking endogenous NT3-TrkC signaling with TrkC-Fc chimera in EXT-success slices strengthened lateral amygdala LTP. Our data support a key role for the NT3-TrkC system in inter-individual differences in fear extinction in rodents, through modulation of amygdalar NMDAR composition and synaptic plasticity.