Biology subjects

Oliva, A.

Publications and source records attributed to Oliva, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Hunger neurons track available food locations during foraging and spatial memory recall

Foraging requires animals to integrate metabolic needs with knowledge of where resources are located. Agouti-related peptide (AgRP) neurons in the hypothalamus are central regulators of appetitive behaviors, yet their role in foraging remains poorly understood. Here, we used fiber photometry to record AgRP neuron activity in freely foraging mice and found that it dynamically tracks spatial proximity to food. AgRP neuron activity decreases progressively as mice approach the food source and increases as they move away, forming a gradient that scales with distance. Notably, this proximity signal emerges only in fasted mice once food is discovered, is specific to the accessible rather than to inaccessible sources, and persists where a source was previously available. Together, our findings reveal that AgRP neuron activity reflects distance to food in a dynamic, experience-dependent manner, extending what these neurons convey beyond internal need and food-related cues to include learned spatial information. HighlightsO_LIAgRP neuron activity reflects spatial distance to food sources during foraging C_LIO_LIAgRP neuron activity gradually decreases on approach to food and increases during departure C_LIO_LIAgRP distance signal depends on metabolic state, and its recall requires visual cues C_LIO_LIAgRP neuron activity tracks food source availability and its location after source removal C_LI

neuroscience↗

bioRxiv2026

Dynamic shifts in brain criticality support cognitive processing

Systems operating near their critical point, or close to a transition between order and disorder, have computational advantages. In the case of neural networks, proximity to criticality is proposed to support optimal brain function. However, different cognitive processes rely on disparate computational demands. Using large-scale electrophysiological recordings in behaving rodents, we examined how critical dynamics in the hippocampus are regulated during learning and sleep-dependent memory consolidation. We found that operating near criticality enables learning by facilitating hippocampal coordination with input regions and maximizing flexibility of neural representations. In contrast, the hippocampal network shifts toward a more ordered, subcritical regime during sleep memory replay, and recovers its proximity to criticality through cholecystokinin interneurons-mediated inhibition. Overall, our findings provide a biophysical substrate for understanding how critical dynamics in neuronal networks can support a variety of brain functions. Importantly, our results suggest that optimal learning systems, whether biological or artificial, may require a dynamic regulation between flexible and rigid states, and can offer biophysical constraints to guide the design of Large Language Models (LLM) tuned to criticality.

neuroscience↗

bioRxiv2025

Drug screening identifies the Src/Abl inhibitor Dasatinib as suppressor of IL-23 signalling in skin inflammation

IL-23-driven IL-17 production by {gamma}{delta}17 and Th17 cells is central to the pathogenesis of psoriasis and other autoimmune disorders. The intracellular mechanisms linking IL-23 signalling to effector cytokine production remain incompletely defined and thus, therapeutic targets downstream of IL-23 are limited. Here, we developed an in vitro model based on a {gamma}{delta}17 T cell line to study IL-23 responses and identify pharmacological inhibitors of type 3 immunity. We conducted a drug-repurposing screening of FDA-approved compounds and identified Src/Abl kinase inhibitors Dasatinib and Bosutinib as potent suppressors of IL-23-induced IL-17A production. In vivo, intraperitoneal and topical Dasatinib administration reduced epidermal thickening, immune cell infiltration, and the accumulation of IL-17-producing T cells in the Imiquimod model of skin inflammation. Mechanistically, Dasatinib and Bosutinib blocked IL-23-dependent mTORC1 and mTORC2 activation. Finally, loss-of-function experiments identified the Src kinase Blk as a critical mediator of IL-23-induced mTORC1 activation and IL-17A production in {gamma}{delta}17 T cells. These findings uncover a novel IL-23-Src-mTOR axis in type 3 immunity, opening the door for therapeutic targeting of Src signalling networks in IL-23/IL-17-driven inflammation.

immunology↗

bioRxiv2025

MOSAIC: A scalable framework for fMRI dataset aggregation and modeling of human vision

Recent large-scale vision fMRI datasets have been invaluable resources to the vision neuroscience community for their deep sampling of individual subjects and diverse stimulus sets. However, practical limitations to the number of subjects, stimuli, and trials that can be collected prevent individual fMRI datasets from reaching the scale necessary for modern modeling approaches and robust conclusions. Here, we introduce MOSAIC (Meta-Organized Stimuli And fMRI Imaging data for Computational modeling), a fMRI dataset aggregation framework designed to leverage the richness of individual datasets for computationally intensive modeling and robust tests of generalization. MOSAIC is composed of eight large-scale vision fMRI datasets totaling 93 subjects, 430,007 fMRI-stimulus pairs, and 162,839 naturalistic and artificial stimuli. A shared fMRI preprocessing pipeline and a filtered test-train split minimizes dataset-specific confounds and test-set leakage when aggregating the datasets. Crucially, additional datasets can be integrated into MOSAIC post hoc, allowing MOSAIC to evolve according to the communitys interests. We use MOSAIC to show that perceptually diverse stimulus sets consistently improve decoding accuracy and stability, carrying implications for future fMRI stimulus set design. We then jointly train brain-optimized encoding models across subjects and datasets to predict fMRI activity of all visual cortex and even the whole brain. In silico functional localizer experiments performed on these digital twin models can recover subject-specific category-selective cortical regions, thereby validating our approach. Together, MOSAIC provides a scalable and community-driven solution to build robust, larger-scale models of human vision.

neuroscience↗

bioRxiv2025

Lauric acid: a promising antimicrobial for the selective inhibition of Staphylococcus epidermidis strains associated with infection

Staphylococcus epidermidis, a human skin colonizer and opportunistic pathogen associated with medical device infections, comprises two phylogenetic lineages: A/C (infection and colonization strains) and B (primarily colonization strains). Given the need for antibiotic alternatives, we investigated the antimicrobial activity of skin-derived fatty acids--lauric, palmitoleic, and linoleic acids--against representative strains from both lineages. Fatty acids reduced exponential growth rate and maximum population, with greater effects on the A/C strain. Lauric and palmitoleic acids decreased colony radius in the B strain. Importantly, lauric acid showed no cytotoxicity on a 3D reconstructed human epidermis model. Our findings demonstrate differential susceptibility between lineages, with A/C strains showing greater sensitivity to all tested fatty acids than B strains. These results highlight the potential of lauric acid as a topical formulation for selective inhibition of S. epidermidis growth, offering a promising approach for preventing pathogenic strain proliferation while preserving beneficial skin colonizers.

microbiology↗

bioRxiv2025

Goal-directed hippocampal theta sweeps during memory-guided navigation

During navigation, animals continually sample their surrounding space and plan routes to distant goals. The brain mechanisms underlying these behaviors and how they coordinate to support memory-guided navigation in open environments are not understood. Using large-scale recordings in rats, we found two distinct types of place cell sequences within theta cycles that encoded trajectories sweeping beyond the animals location: stereotypic left-right alternating sweeps and learning-dependent goal-directed sweeps. Goal-directed sweeps predicted upcoming trajectories to remembered goal locations, were coordinated with prefrontal cortex activity and preferentially replayed during sharp-wave ripples. We further describe a circuit mechanism in which a subpopulation of CA1 cells encodes egocentric goal direction, combined with reduced feedback inhibition, to generate goal-directed theta sweeps. These results indicate a flexible mechanism to support different behavioral demands during navigation.

neuroscience↗

bioRxiv2025

Large sharp-wave ripples promote hippocampo-cortical memory reactivation and consolidation

During sleep, ensemble activity patterns encoding recent experiences are reactivated in the hippocampus and cortex. This reactivation is coordinated by hippocampal sharp-wave ripples (SWRs) and is believed to support the early stages of memory consolidation. However, only a minority of sleep SWRs are associated with memory reactivation in the hippocampus and its downstream areas. Whether that subset of SWRs have specific physiological characteristics and directly contribute to memory performance is not known. We identified a specific subset of large SWRs linked to memory reactivation in both the hippocampus and prefrontal cortex (PFC) of mice, and found that their occurrence selectively increased during sleep following new learning. Closed-loop optogenetic SWR boosting during sleep was sufficient to enhance ensemble memory reactivation in hippocampus and PFC. This manipulation also improved subsequent memory retrieval and hippocampal-PFC coordination during waking, causally linking both phenomena to SWR-associated ensemble reactivation during sleep.

neuroscience↗

bioRxiv2025

A hippocampal population code for rapid generalization

Generalizing from experience and applying prior knowledge to new situations is essential for intelligent behavior. Traditional models attribute this generalization to gradual statistical learning in the neocortex. However, such a slow process cannot account for animals rapid generalization from limited experience. Here, we demonstrate that the hippocampus supports rapid generalization in mice by generating disentangled memory representations, where different aspects of experience are encoded independently. This code enabled the transfer of prior knowledge to solve new tasks. We identify specific circuit mechanisms underlying this rapid generalization. We show that the seemingly random changes in individual neuronal activity over time and across environments result from structured circuit-level processes, governed by the dynamics of local inhibition and cross-regional cell assemblies, respectively. Our findings provide computational and mechanistic insights into how the geometric structure and underlying circuit organization of hippocampal population dynamics facilitate both memory discrimination and generalization, enabling efficient and flexible learning.

neuroscience↗

bioRxiv2024

Touch to text: Spatiotemporal evolution of braille letter representations in blind readers

Visual deprivation does not silence the visual cortex, which is responsive to auditory, tactile, and other nonvisual tasks in blind persons. However, the underlying functional dynamics of the neural networks mediating such crossmodal responses remain unclear. Here, using braille reading as a model framework to investigate these networks, we presented sighted (N=13) and blind (N=12) readers with individual visual print and tactile braille alphabetic letters, respectively, during MEG recording. Using time-resolved multivariate pattern analysis and representational similarity analysis, we traced the alphabetic letter processing cascade in both groups of participants. We found that letter representations unfolded more slowly in blind than in sighted brains, with decoding peak latencies [~]200 ms later in braille readers. Focusing on the blind group, we found that the format of neural letter representations transformed within the first 500 ms after stimulus onset from a low-level structure consistent with peripheral nerve afferent coding to high-level format reflecting pairwise letter embeddings in a text corpus. The spatiotemporal dynamics of the transformation suggest that the processing cascade proceeds from a starting point in somatosensory cortex to early visual cortex and then to inferotemporal cortex. Together our results give insight into the neural mechanisms underlying braille reading in blind persons and the dynamics of functional reorganization in sensory deprivation.

neuroscience↗

bioRxiv2023

BOLD Moments: modeling short visual events through a video fMRI dataset and metadata

Studying the neural basis of human dynamic visual perception requires extensive experimental data to evaluate the large swathes of functionally diverse brain neural networks driven by perceiving visual events. Here, we introduce the BOLD Moments Dataset (BMD), a repository of whole-brain fMRI responses to over 1,000 short (3s) naturalistic video clips of visual events across ten human subjects. We use the videos extensive metadata to show how the brain represents word- and sentence-level descriptions of visual events and identify correlates of video memorability scores extending into the parietal cortex. Furthermore, we reveal a match in hierarchical processing between cortical regions of interest and video-computable deep neural networks, and we showcase that BMD successfully captures temporal dynamics of visual events at second resolution. With its rich metadata, BMD offers new perspectives and accelerates research on the human brain basis of visual event perception.

neuroscience↗

bioRxiv2023

Hippocampal area CA2 controls seizure dynamics, interictal EEG abnormalities and social comorbidity in mouse models of temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, abnormal activity between seizures, and impaired behavior. CA2 pyramidal neurons (PNs) are potentially important because inhibiting them with a chemogenetic approach reduces seizure frequency in a mouse model of TLE. However, whether seizures could be stopped by timing inhibition just as a seizure begins is unclear. Furthermore, whether inhibition would reduce the cortical and motor manifestations of seizures are not clear. Finally, whether interictal EEG abnormalities and TLE comorbidities would be improved are unknown. Therefore, real-time optogenetic silencing of CA2 PNs during seizures, interictal activity and behavior were studied in 2 mouse models of TLE. CA2 silencing significantly reduced seizure duration and time spent in convulsive behavior. Interictal spikes and high frequency oscillations were significantly reduced, and social behavior was improved. Therefore, brief focal silencing of CA2 PNs reduces seizures, their propagation, and convulsive manifestations, improves interictal EEG, and ameliorates social comorbidities. HIGHLIGHTSO_LIReal-time CA2 silencing at the onset of seizures reduces seizure duration C_LIO_LIWhen CA2 silencing reduces seizure activity in hippocampus it also reduces cortical seizure activity and convulsive manifestations of seizures C_LIO_LIInterictal spikes and high frequency oscillations are reduced by real-time CA2 silencing C_LIO_LIReal-time CA2 silencing of high frequency oscillations (>250Hz) rescues social memory deficits of chronic epileptic mice C_LI

neuroscience↗

bioRxiv2022

Hippocampo-cortical circuits for selective memory encoding, routing, and replay

Traditionally considered a homogeneous cell type, hippocampal pyramidal cells have been recently shown to be highly diverse. However, how this cellular diversity relates to the different hippocampal network computations that support memory-guided behavior is not yet known. We discovered that the anatomical identity of pyramidal cells is a major organizing principle of CA1 assembly dynamics, the emergence of memory replay, and cortical projection patterns. Segregated pyramidal cell subpopulations encoded trajectory and choice-specific information or tracked changes in reward configuration respectively, and selectively routed these representations to different cortical targets. Furthermore, distinct hippocampo-cortical assemblies coordinated the reactivation of complementary memory representations. These findings reveal the existence of specialized hippocampo-cortical subcircuits and provide a cellular mechanism that supports the computational flexibility and memory capacities of these structures.

neuroscience↗

bioRxiv2022

The time to initiate retrieval of a memory depends on recency

Continuous recognition has long been used to study the recency effect in recognition memory. In continuous recognition, response time (RT) increases as a logarithmic function of the lag since a probe was last presented. Although this could simply be due to decaying trace strength, careful examination of response time (RT) distributions showed that the onset of RT distributions changed with the logarithm of the lag since a probe was originally presented. Each doubling of lag resulted in a shift of roughly 20 ms in the rise time of the RT distributions. To test the hypothesis that this increase was simply due to increased facility in processing the probe item, Experiment six repeated items six times. Repetition resulted in faster RTs, but did not change the effect of log lag on RT. In light of recent neurophysio-logical evidence, we consider the hypothesis that memory requires a recovery of temporal context, and the time to retrieve a prior temporal context goes up with the logarithm of the time since it was experienced.

animal behavior and cognition↗

bioRxiv2022

A resistome survey across hundreds of freshwater bacterial communities reveals the impacts of veterinary and human antibiotics use

Our decreasing ability to fight bacterial infections is a major health concern. It is arising due to the evolution of antimicrobial resistance (AMR) in response to the mis- and overuse of antibiotics in both human and veterinary medicine. Lakes integrate watershed processes and thus may act as receptors and reservoirs of antibiotic resistance genes (ARGs) introduced into the watershed by human activities. The resistome - the diversity of ARGs - under varying anthropogenic watershed pressures has been previously studied either focused on few select genes or few lakes. Here, we link the resistome of [~]350 lakes sampled across Canada to human watershed activity, trophic status, as well as point sources of ARG pollution. A high percentage of the resistance genes detected was either unimpacted by human activity or highly prevalent in pristine lakes, highlighting the role of AMR in microbial ecology in aquatic systems, as well as a pool of genes available for potential horizontal gene transfer to pathogenic species. Nonetheless, watershed agricultural and pasture area significantly impacted the resistome. Moreover, the number of hospitals and the population density in a watershed, the volume of wastewater entering the lake, as well as the fraction of manure applied in the watershed as fertilizer significantly impacted ARG diversity. Together, these findings indicate that lake resistomes are regularly stocked with resistance genes evolved in the context of both veterinary and human antibiotics use and represent reservoirs of ARGs that require further monitoring.

genomics↗

bioRxiv2022

Reconstructed human pigmented skin/epidermis models achieve epidermal pigmentation through melanocore transfer.

The skin acts as a barrier to environmental insults and provides many vital functions. One of these is to shield DNA from harmful UV radiation, which is achieved by skin pigmentation arising as melanin is produced and dispersed within the epidermal layer. This is a crucial defence against DNA damage, photo-ageing and skin cancer. The mechanisms and regulation of melanogenesis and melanin transfer involve extensive crosstalk between melanocytes and keratinocytes in the epidermis, as well as fibroblasts in the dermal layer. Although the predominant mechanism of melanin transfer continues to be debated and several plausible models have been proposed, we and others previously provided evidence for a coupled exo/phagocytosis of melanocore model. Herein, we performed histology and immunohistochemistry analyses and demonstrated that a newly developed full-thickness 3D reconstructed human pigmented skin model and an epidermis-only model exhibit dispersed pigment throughout keratinocytes in the epidermis. Transmission electron microscopy revealed melanocores between melanocytes and keratinocytes, suggesting that melanin is transferred through coupled exocytosis/phagocytosis of the melanosome core similar to our previous observations in human skin biopsies. We therefore present evidence that our in vitro models of pigmented human skin show epidermal pigmentation comparable to human skin. These findings have a high value for studies of skin pigmentation mechanisms and pigmentary disorders, whilst reducing the reliance on animal models and human skin biopsies. SignificanceCurrently, many approaches to study skin pigmentation and pigmentary disorders use 2D cultures or co-culture of melanocytes and/or keratinocytes, as well as skin biopsies obtained from consenting donors. However, challenges are faced when it is necessary to mimic the tissue microenvironment as there is a limited availability of skin biopsies, especially for the case of rare pigmentary disorders. Through this study, we show the potential of 3D in vitro reconstructed pigmented skin/epidermis models for both general and specific pigmentary research questions, which could reduce reliance on animal models and human skin biopsies.

cell biology↗

bioRxiv2021

Aging-related olfactory loss is associated with olfactory stem cell transcriptional alterations in humans

Presbyosmia, or aging related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) in the nasal fossa is the peripheral organ for olfaction, and is subject to acquired damage, suggesting a likely site of pathology in aging. OE basal stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis or repair. Accordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. Combining psychophysical testing with olfactory mucosa biopsy analysis, single cell RNA-sequencing (scRNA-seq), and human olfactory culture studies, we identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress, or the regulation of proliferation and differentiation. To facilitate further study of human OE stem cells, we developed an adult human basal cell culture model. Characterization of cultures using scRNA-seq confirmed maintenance of a reserve stem cell-like phenotype, and brief cytokine exposure in basal cell cultures resulted in increased expression of TP63, a transcription factor acting to prevent OE stem cell differentiation. Our data are consistent with a process by which aging-related inflammatory changes in OE stem cells may contribute to presbyosmia, via the disruption of normal epithelial homeostasis, suggesting that OE stem cells may represent a rational therapeutic target for restoration of olfaction. One Sentence SummarySingle cell profiling suggests that inflammatory-associated olfactory epithelial stem cell dysfunction is associated with presbyosmia in humans.

neuroscience↗

bioRxiv2021

BWA-mem is not the best aligner for ancient DNA short reads.

Xu and colleagues (Xu et al., 2021) recently suggested a new parameterisation of BWA-mem (Li, 2013) as an alternative to the current standard BWA-aln (Li and Durbin, 2009) to process ancient DNA sequencing data. The authors tested several combinations of the -k and -r parameters to optimise BWA-mems performance with degraded and contaminated ancient DNA samples. They report that using BWA-mem with -k 19 -r 2.5 parameters results in a mapping efficiency comparable to BWA-aln with -I 1024 -n 0.03 (i.e. a derivation of the standard parameters used in ancient DNA studies; (Schubert et al., 2012)), while achieving significantly faster run times. We recently performed a systematic benchmark of four mapping software (i.e. BWA-aln, BWA-mem, NovoAlign (http://www.novocraft.com/products/novoalign), and Bowtie2 (Langmead and Salzberg, 2012) for ancient DNA sequencing data and quantified their precision, accuracy, specificity, and impact on reference bias (Oliva et al., 2021). Notably, while multiple parameterisations were tested for BWA-aln, NovoAlign, and Bowtie2, we only tested BWA-mem with default parameters. Here, we use the alignment performance metrics from Oliva et al. to directly compare the recommended BWA-mem parameterisation reported in Xu et al. with the best performing alignment methods determined in the Oliva et al. benchmarks, and we make recommendations based on the results.

bioinformatics↗

bioRxiv2020

Spatiotemporal Dynamics of Sound Representations Reveal a Hierarchical Progression of Category Selectivity

As the human brain transforms incoming sounds, it remains unclear whether semantic meaning is assigned via distributed, domain-general architectures or specialized hierarchical streams. Here we show that the spatiotemporal progression from acoustic to semantically dominated representations is consistent with a hierarchical processing scheme. Combining magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) patterns, we found superior temporal responses beginning ~80 ms post-stimulus onset, spreading to extratemporal cortices by ~130 ms. Early acoustically-dominated representations trended systematically toward semantic category dominance over time (after ~200 ms) and space (beyond primary cortex). Semantic category representation was spatially specific: vocalizations were preferentially distinguished in temporal and frontal voice-selective regions and the fusiform face area; scene and object sounds were distinguished in parahippocampal and medial place areas. Our results are consistent with an extended auditory processing hierarchy in which acoustic representations give rise to multiple streams specialized by category, including areas typically considered visual cortex.

neuroscience↗