bioRxiv Science⌕ Search

Biology subjects

Silva, N. J.

Publications and source records attributed to Silva, N. J..

9 recordsLinked to original sources

Sex-specific Flexibility in Breeding and Helping Strategies in the Sociable Weaver (Philetairus socius)

Helping-at-the-nest is often viewed as a precursor to reproduction, but switching between breeder and helper roles has been documented in some species. Such flexibility should depend on the opportunities and benefits of helping, which could differ between sexes due to dispersal strategies and social structure. However, whether breeding-helping flexibility is widespread and sex-specific remains unknown. Here, we investigated sex-specific strategies in breeding-helping flexibility using a 10-year dataset (1955 individuals) on sociable weavers (Philetairus socius), a colonial cooperative breeder in which males are typically philopatric whereas females disperse. Both sexes helped for several years, with males helping more frequently than females and for twice as long (0-13 vs 0-10 years). Around 40% of non-dispersing birds never became breeders and 50% of individuals bred without helping first. Both sexes switched roles between- and within-seasons but males were more likely to alternate (respectively four and six times more than females and up 15 switches across seven years). Our study reveals important flexibility and sex differences in breeder-helper roles, consistent with sex-biased dispersal, spatial breeding proximity and possible indirect fitness benefits. These factors could play a role promoting the evolution of helping across life-stages, not only pre-reproduction, but also reproductive and post-reproductive individuals.

evolutionary biology↗

Extracellular matrix proteolysis maintains synapse plasticity during brain development

Maintaining a dynamic neuronal synapse pool is critical to brain development. The extracellular matrix (ECM) regulates synaptic plasticity via mechanisms that are still being defined and are studied predominantly in adulthood. Using live imaging of excitatory synapses in zebrafish hindbrain we observed a bimodal distribution of short-lived (dynamic) and longer-lived (stable) synapses. Disruption of ECM via digestion or brevican deletion destabilized dynamic but not stable synapses and led to decreased synapse density. Conversely, loss of matrix metalloproteinase 14 (MMP14) led to accumulation of brevican and increased the stable synapse pool, resulting in increased synapse density. Microglial MMP14 was essential to these effects in both fish and human iPSC-derived cultures. Both MMP14 and brevican were required for experience-dependent synapse plasticity in a motor learning assay. These data, complemented by mathematical modeling, define an essential role of ECM remodeling in maintaining a dynamic subset of synapses during brain development.

neuroscience↗

Long-term evaluation of the association between dominance, bib size, sex and age

The association between dominance and phenotypic traits ( badges of status) has been recently questioned, since it has been found to show more variation across populations and time than expected. Using an eleven-year dataset, encompassing more than 1,800 individuals, we studied the association between the size of a melanin-based plumage trait (a black patch under the beak or bib), individual attributes (age and sex) and dominance. Our study model, the sociable weaver (Philetairus socius), is a small passerine, which lives year-round in colonies of varying size. Bib sizes were obtained from pictures and automatically pre-processed with an object segmentation deep learning network. We recorded 36,346 dominance-related interactions to estimate dominance hierarchies. We then investigated the effect of sex and age on bib size, and the overall and between-year association of bib size and age with dominance for each sex. We found that bib size increased with age within individuals of both sexes. Age was a strong and consistent predictor of dominance in males, but not in females. Nevertheless, dominance was not correlated with bib size in males and in females. Finally, these relationships did not strongly vary between years. Our results suggest that males and females may use different factors to regulate dominance interactions. Furthermore, our longitudinal dataset allowed us to show that bib size is not a badge of status in our population even though its growth encodes information on age. These results highlight the importance of considering multiple traits over time when studying morphological signalling of dominance hierarchy.

animal behavior and cognition↗

Type 1 lymphocytes and interferon-γ accumulate in the thalamus and restrict seizure susceptibility after traumatic brain injury

Chronic neural circuit hyperexcitability frequently emerges after brain injury, but endogenous mechanisms constraining runaway activity remain poorly understood. Here, we reveal that the adaptive immune system acts as a homeostatic brake on network excitability following traumatic brain injury (TBI). In mice, cortical trauma triggered a delayed infiltration of interferon-{gamma} (IFN{gamma})-producing type 1 lymphocytes into the sensory thalamus. Rather than driving pathology, IFN{gamma} signaling directly in neurons restricted thalamocortical network hyperexcitability. This protective axis was tonically regulated; depleting CD4 T cells de-repressed local non-CD4 type 1 lymphocytes, elevating IFN{gamma} signaling and protecting from seizures. A single dose of exogenous IFN{gamma} abolished hypersynchronous circuit bursting and rescued injury-induced seizure incidence, severity, and mortality, establishing a therapeutic framework for safeguarding circuit stability after brain injury.

immunology↗

Microglial cathepsin B promotes neuronal efferocytosis during brain development

Half of all newborn neurons in the developing brain are removed via efferocytosis - the phagocytic clearance of apoptotic cells. Microglia are brain-resident professional phagocytes that play important roles in neural circuit development including as primary effectors of efferocytosis. While the mechanisms through which microglia recognize potential phagocytic cargo are widely studied, the lysosomal mechanisms that are necessary for efficient digestion are less well defined. Here we show that the lysosomal protease cathepsin B promotes microglial efferocytosis of neurons and restricts the accumulation of apoptotic cells during brain development. We show that cathepsin B is microglia-specific and enriched in brain regions where neuronal turnover is high in both zebrafish and mouse. Myeloid-specific cathepsin B knockdown in zebrafish led to dysmorphic microglia containing undigested dead cells, as well as an accumulation of dead cells in surrounding tissue. These effects where phenocopied in mice globally deficient for Ctsb using markers for apoptosis. We also observed behavioral impairments in both models. Live imaging studies in zebrafish revealed deficits in phagolysosomal fusion and acidification, and live imaging of cultured mouse microglia reveal delayed phagocytosis consistent with impairments in digestion and resolution of phagocytosis rather than initial uptake. These data reveal a novel role for microglial cathepsin B in mediating neuronal efferocytosis during typical brain development.

neuroscience↗

A deep learning approach to detect and visualise sexual dimorphism in monomorphic species

Sex recognition is facilitated by dimorphism in some traits. However, humans often fail to find the traits that allow to distinguish between sexes in other species. Deep learning has the potential to surpass humans in identifying cryptic differences between sexes, but, so far, has rarely been used to assess sexual dimorphism. In this study, we evaluated (i) the ability of a fine-tuned classification neural network, EfficientNet, to find differences between sexes in a species that appears monomorphic to humans, the sociable weaver (Philetairus socius). We then assessed (ii) the benefits of Grad-CAM visualisation techniques to understand which parts of the individuals are used by the network to differentiate the sexes. We trained 10-folds cross-validation models on more than 4,500 pictures of the head from more than 1,300 individuals. Our results show that the network can predict sex of sociable weavers with an accuracy of 76%, which is considerably higher than humans performance, and that the model was similarly good at predicting females and males. When interpreting the probability of being classified to one sex, our results further reveal an effect of the interaction of sex with age on the confidence score of the models which shows that younger males are less masculine than older ones, and older females more masculine than younger ones. Finally, using Grad-CAM we found that the model mostly uses the beak region to predict the sex of individuals. Overall, this work shows that artificial intelligence has the potential to be a non-invasive sexing tool, surpassing human capabilities and aiding in pinpointing potential cryptic dimorphic body parts that have yet to be identified. In birds, half of the worlds species appear sexually monomorphic to humans, and re-evaluation of species dimorphism with this type of methods could deepen our understanding of the effect of selection on animal traits.

zoology↗

Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina.

Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes. This regeneration requires Muller glia (MG) to reprogram and divide asymmetrically to produce a multipotent Muller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, does loss of different retinal cell subtypes induce unique MG regeneration responses? Second, do MG reprogram to a developmental retinal progenitor cell state? And finally, to what extent does regeneration recapitulate retinal development? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. While MG reprogram to a state similar to late-stage retinal progenitors in developing retinas, there are transcriptional differences between reprogrammed MG/MGPCs and late progenitors, as well as reprogrammed MG in outer and inner retinal damage models. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes. This work identifies major differences between gene regulatory networks activated following the selective loss of different subtypes of retina neurons, as well as between retinal regeneration and development.

neuroscience↗

In situ and transcriptomic identification of synapse-associated microglia in the developing zebrafish brain

Microglia are brain resident macrophages that play vital roles in central nervous system (CNS) development, homeostasis, and pathology. Microglia both remodel synapses and engulf apoptotic cell corpses during development, but whether unique molecular programs regulate these distinct phagocytic functions is unknown. Here we identify a molecularly distinct synapse-associated microglial subset in the zebrafish (Danio rerio). We found that ramified microglia populated synapse-rich regions of the midbrain and hindbrain between 7 and 28 days post fertilization. In contrast, microglia in the optic tectum were ameboid and clustered around neurogenic zones. Using single-cell mRNA sequencing combined with metadata from regional bulk sequencing, we identified synapse-associated microglia (SAMs) that were highly enriched in the hindbrain, expressed known synapse modulating genes as well as novel candidates, and engulfed synaptic proteins. In contrast, neurogenic-associated microglia (NAMs) were enriched in optic tectum, had active cathepsin activity, and preferentially engulfed neuronal corpses. These data yielded a functionally annotated atlas of zebrafish microglia (https://www.annamolofskylab.org/microglia-sequencing). Furthermore, they reveal that molecularly distinct phagocytic programs mediate synaptic remodeling and cell engulfment, and establish zebrafish hindbrain as a model circuit for investigating microglial-synapse interactions.

neuroscience↗

Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in the adult zebrafish

Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the zebrafish retina and determine the cellular expression and function of the inflammatory protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Following sterile photoreceptor ablation anti-inflammatory treatment suppresses both the number of injury-induced progenitors and regenerated photoreceptors. Upon photoreceptor injury, mmp-9 is induced in Muller glia, the intrinsic retinal stem cell, and Muller glia-derived photoreceptor progenitors. Deleting mmp-9 results in over production of injury-induced progenitors and regenerated photoreceptors, but over time the absence of Mmp-9 compromises the maturation and survival of the regenerated cones. Anti-inflammatory treatment in mutants rescues the defects in cone maturation and survival. These data provide a link between injury-induced inflammation in the vertebrate CNS, Mmp-9 function during photoreceptor regeneration and the requirement of Mmp-9 for the survival of regenerated cones. Significance StatementThe innate immune system is activated by neuronal death, and recent studies demonstrate that in zebrafish neuroinflammation is required for neuronal regeneration. The roles of inflammatory cytokines are being investigated, however, the function of the inflammatory protease, matrix metalloprotease Mmp-9, in neuronal regeneration is unknown. We show herein that in adult zebrafish retinal inflammation governs the proliferative phase of the stem cell-based regeneration of rod and cone photoreceptors and determine the specific roles for Mmp-9 in photoreceptor regeneration. This study provides the first mechanistic insights into the potential role of Mmp-9 and serves to link neuroinflammation, stem cell-based regeneration of photoreceptors and human photoreceptor disease.

neuroscience↗