Biology subjects

Landry, M.

Publications and source records attributed to Landry, M..

At least 19 recordsLinked to original sources

bioRxiv2026

A PTBP1-CDC42 splicing axis regulates leukemia growth and venetoclax sensitivity in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by high rates of relapse and poor outcomes, especially in elderly or unfit patients, who cannot tolerate intensive chemotherapy. While the BCL2 inhibitor venetoclax has improved initial responses in this high-risk population, relapses remain nearly universal, highlighting the need for novel therapeutic strategies. Here, we identify the RNA-binding protein PTBP1 as a critical dependency in AML. PTBP1 depletion impairs leukemic growth in vitro and in vivo, and is associated with widespread splicing alterations and global disruption of protein synthesis. Integrative transcriptomic and iCLIP analyses reveal that PTBP1 orchestrates a splicing program centered on Rho GTPase signaling, with CDC42 as a key downstream effector. Mechanistically, PTBP1 loss triggers a splicing switch from CDC42-v1 to CDC42-v2, leading to reduced GTPase activity and impaired protein synthesis. Pharmacological inhibition of CDC42 selectively induces cytotoxicity in AML cells, while sparing healthy hematopoietic cells. Importantly, CDC42 inhibition markedly enhances venetoclax anti-leukemic efficacy. These findings establish PTBP1 as a critical regulator of AML cell fitness and identify a clinically actionable therapeutic combination that exploits AML dependency on PTBP1-CDC42 signaling to enhance the efficacy of venetoclax-based regimens.

cancer biology↗

bioRxiv2026

From language to pain: brain-behavior representations of hypnotic verbal suggestions for pain modulation

Language can shape pain by conveying conceptual information about future somatosensory experiences. However, how verbal input is encoded in the brain and how these representations are later implemented during pain modulation remains unclear. We used a standardized hypnotic procedure with fMRI to test how verbal suggestions of hypoalgesia and hyperalgesia (vs neutral control) modulate pain. We quantified convergent neural responses across individuals during both suggestion encoding and pain processing, using inter-subject correlation and multivoxel pattern similarity approaches, respectively, and related these measures to individual differences in hypnotic suggestibility using representational similarity analysis. More suggestible individuals showed similar temporal dynamics in language-related regions during encoding and more similar hypoalgesia-specific patterns in the left parahippocampal gyrus (PHG) during pain. In contrast, lower suggestibility was associated with convergent responses in sensorimotor and monitoring systems across phases, demonstrating different neural implementation in individuals less successful in converting suggestions into hypoalgesia. These findings identify the PHG as a key region linking the effect of verbal suggestions to subsequent pain relief and show that hypnotic suggestibility structures how neural dynamics during language processing translate into altered pain experiences. This study offers a mechanistic lens for understanding how medical hypnosis and language-based therapies influence pain.

neuroscience↗

bioRxiv2025

Primary productivity and N2-fixation in the eastern Indian Ocean: bottom-up support for an ecologically and economically important ecosystem

Oligotrophic regions of the global ocean are characterized by strong nutrient limitation, low standing phytoplankton biomass, and highly efficient nutrient recycling. We quantified nutrient inventories, primary productivity and N2 fixation during the BLOOFINZ-IO expedition (February 2022) in the Argo Basin located in the eastern Indian Ocean, the sole known spawning ground for Southern Bluefin Tuna. Surface nitrate concentrations were near depletion (<0.02 {micro}mol L-1), with low but persistent residual phosphate (P) concentrations suggesting nitrogen as the major limiting nutrient. Depth-integrated net primary production (NPP), from 14C-based in-situ incubations during 4 Lagrangian cycles, averaged [~]460 mg C m-2d-1, in good agreement with satellite-based NPP estimates. Nitrogen fixation provided a consistent new nitrogen source, contributing [~]16% to local NPP in the upper euphotic zone. Gross primary production (GPP), derived from fast-repetition-rate-fluorometry-based electron transport estimates, revealed significant autotrophic respiration losses, with GPP:NPP ratios averaging [~]1.8, consistent with metabolic costs under nutrient limitation. Net community production (NCP), estimated from O2/Ar ratios, remained positive across all cycles, averaging [~]20% of NPP in the upper 30 m. This result, in combination with N2 fixation measurement indicates that N2 fixation supports most of the export production in this region. Together, the multi-method approach revealed a recycling-dominated ecosystem affected by episodic mixing events, where primary productivity is maintained primarily through efficient nitrogen recycling and physiological photoacclimation. These results provide a comprehensive baseline of bottom-up support on ecosystem productivity for the Argo Basin for assessing future climate-driven changes in stratification, nutrient cycling, and food-web dynamics.

ecology↗

bioRxiv2025

Intrinsic Neural Oscillations Predict Verbal Learning Performance and Encoding Strategy Use

Individuals adopt different encoding strategies to facilitate learning. However, few studies have investigated the neurophysiological basis that support these different encoding strategies across individuals. The present work addresses this gap by extending our previous findings on the direct relationship between cortical spectral power, measured via resting-state magnetoencephalography, and performance on standard cognitive test results. Our results highlight the complex interactions between endogenous brain oscillations, learning and verbal encoding strategies assessed by the California Verbal Learning Test (CVLT-2). First, we found that resting-state theta oscillations were significantly associated with verbal learning and subjective clustering strategies. Second, we observed that semantic clustering is facilitated by oscillatory patterns in left sensory-motor brain regions. Finally, our analyses revealed that serial and semantic clustering strategies are related to opposite regression patterns, indicating a competitive interaction. Together, these findings provide novel insights into the neural oscillatory dynamics that support diverse encoding strategies in verbal learning.

neuroscience↗

bioRxiv2025

Quantifying Rhythmic and Arrhythmic Components of Brain Activity

Brain activity comprises both rhythmic (periodic) and arrhythmic (aperiodic) components. These signal elements vary across healthy aging, and disease, and may make distinct contributions to conscious perception. Despite pioneering techniques to parameterize rhythmic and arrhythmic neural components based on power spectra, the methodology for quantifying rhythmic activity remains in its infancy. Previous work has relied on parametric estimates of rhythmic power extracted from specparam, or estimates of rhythmic power obtained after detrending neural spectra. Variation in analytical choices for isolating brain rhythms from background arrhythmic activity makes interpreting findings across studies difficult. Whether these current approaches can accurately recover the independent contribution of these neural signal elements remains to be established. Here, using simulation and parameter recovery approaches, we show that power estimates obtained from detrended spectra conflate these two neurophysiological components, yielding spurious correlations between spectral model parameters. In contrast, modelled rhythmic power obtained from specparam, which detrends the power spectra and parametrizes brain rhythms, independently recovers the rhythmic and arrhythmic components in simulated neural time series, minimising spurious relationships. We validate these methods using resting-state recordings from a large cohort. Based on our findings, we recommend modelled rhythmic power estimates from specparam for the robust independent quantification of rhythmic and arrhythmic signal components for cognitive neuroscience.

neuroscience↗

bioRxiv2025

Phytoplankton community structure and photophysiological strategies in the oligotrophic Indian Ocean spawning ground of Southern Bluefin Tuna

The Argo Basin, a persistently oligotrophic seascape downstream of the Indonesian Throughflow (ITF), is the only known spawning ground of Southern Bluefin Tuna (Thunnus maccoyii). Its surface waters are capped by the warm, low saline, nitrate-depleted Pacific Ocean outflow, that leads to intense water-column stratification and chronic nutrient scarcity. During the BLOOFINZ campaign (R/V Roger Revelle, January-March 2022), we combined high-resolution underway surveys with Lagrangian experiments to examine hydrography, nutrient stoichiometry, and phytoplankton photophysiology across the basin. This study was motivated by the need to: 1) identify the phytoplankton communities capable of persisting in this nutrient-impoverished region, and 2) uncover the unique photophysiological traits that underpin their survival and growth, particularly under acute nitrate limitation. Nutrient fields revealed strongly negative N*, positive Si*, and elevated Si:P ratios, indicating a system of acute nitrate scarcity but with residual phosphate and latent silicate availability. Phytoplankton communities were dominated by the cyanobacteria, Prochlorococcus, whose survival strategies included small functional absorption cross section of PSII ({sigma}PSII), enhanced PSII connectivity (p), highly elastic and reversible diel photophysiology that balanced high-light stress and nitrogen scarcity. Longer turnover times especially {tau}2 ({micro}s; PSII-PSI electron transport) seen in the region around 115{degrees} and 120{degrees}E and at 15{degrees}S, and during Cycles 3 and 4 are indicative of populations that were being stressed by Fe limitation as well. Our inference of Prochlorococcus is supported by complimentary measurements of flow cytometry, phytoplankton pigment composition and microscopy all of which confirmed the dominance of Prochlorococcus in these nutrient impoverished waters. Our observations further indicate that mesoscale eddies generated by ITF-SICC (South Indian Counter Current) interactions, can episodically shoal the nutricline, triggering transient pulses of larger eukaryotes. Collectively, these results demonstrate how acute nitrate depletion, compounded by Fe stress, structures a microbial community finely tuned to oligotrophy and capable of sustaining a short food chain involving appendicularians that directly support larval tuna. The Argo Basin therefore exemplifies how circulation-nutrient coupling shapes microbial communities and ecosystem function within a globally significant spawning habitat. Highlights1) Chronic nitrate limitation, with strongly negative N* and persistent N:P imbalance defines the Argo Basin while phosphate and silicate remain in relative excess. 2) Picocyanobacteria especially Prochlorococcus dominate the ecosystem, sustaining productivity under extreme oligotrophy through photophysiological strategies of reduced {sigma}PSII, enhanced PSII connectivity, and diel recovery from light stress. 3) Mesoscale eddies at the ITF-SICC front provide episodic relief, shoaling the nutricline and fueling transient pulses of larger phytoplankton that episodically reshape phytoplankton community structure and biomass 4) This oligotrophic-frontal seascape supports a short, efficient food web, enabling transfer of picophytoplankton to Southern Bluefin Tuna larvae via mainly appendicularians.

ecology↗

bioRxiv2025

Nucleus raphe magnus serotonin neurons bidirectionally control spinal mechanical pain transmission

BackgroundNoxious stimuli are conveyed to and integrated in the dorsal horn of the spinal cord (DHSC) before being transmitted to supraspinal centers, where pain perception is generated. Descending pathways from the brainstem dynamically modulate this integration, either facilitating or inhibiting nociceptive information based on physiological, emotional, genetic and environmental factors. Serotonergic neurons in the nucleus raphe magnus (NRM), activating different spinal 5-HT receptors, exert bidirectional control, both facilitatory and inhibitory, but the underlying mechanisms of this control remain unclear. MethodsWe investigated in adult mice, the NRM serotonergic modulation of nociception using imaging, behavioral, pharmacological, electrophysiological, chemogenetic and optogenetic approaches. ResultsWe have demonstrated that the action of serotonergic neurons in the NRM on spinal nociceptive transmission depends on their activation pattern, which targets different spinal 5-HT receptors likely associated with different spinal microcircuits. Serotonergic neurons of the NRM exert a tonic analgesic effect mediated by 5-HT2c receptor. Low increase in 5-HT activity leads to an increased analgesia through spinal inhibitory interneurons expressing 5-HT2c and 5-HT2A receptors. Finally, prolonged stimulation of serotonergic neurons led to hyperalgesia mediated by 5-HT3 receptor. Comparison of 5-HT receptors in spinal tissue from mice and human shows that 5-HT2c receptor has a very high expression level, comparable between both species. ConclusionsThese results propose a model of bidirectional action of serotonin neurons on nociceptive transmission depending on their level of activity and show that 5-HT2c receptor is the main mediator of serotonin-induced analgesia.

neuroscience↗

bioRxiv2025

A subset of dorsal raphe dopamine neurons is critical for survival-oriented vigilance.

Defensive behaviors are essential for survival, with risk assessment enabling organisms to evaluate and respond to potential threats. The dorsal raphe nucleus (DRN), a key neuromodulatory center, is crucial for encoding motivational salience and regulating arousal and sleep-wake states through its diverse neuronal populations, including dopaminergic neurons (DRNDA). While the roles of DRNDA neurons have been studied, their specific contributions to threat evaluation are less understood. Recent research identifies a distinct subset of DRNDA neurons that express vasoactive intestinal peptide (VIP) and project to the central amygdala (CeA) and the oval nucleus of the bed nucleus of the stria terminalis (ovBNST). Together, these two regions comprise the central extended amygdala, a key network regulating adaptive responses to threats. We hypothesized that distinct DRNDA subpopulations exert diverging effects on sleep-wake regulation and that DRNVIP neurons play a pivotal role in coordinating activity between the CeA and ovBNST, thereby influencing risk assessment and defensive response. To test this hypothesis, we used a combination of in situ hybridization, immunochemistry, whole-brain mapping, electrophysiology, and cell-specific genetic tools in mice and non-human primates. Our findings reveal that DRNVIP neurons form a key DRNDA neuronal subset, uniquely positioned to regulate the central extended amygdala through a feedback loop. These neurons receive inputs from Protein Kinase C delta (PKC-{delta}) neurons in the ovBNST and CeA and send glutamate-releasing projections back to these regions, modulating PKC-{delta} neuron excitability. Selective ablation of DRNVIP neurons increases activity in both the BNST and CeA, disrupting active-phase sleep architecture and impairing risk assessment and defensive behaviors. Together, these findings suggest DRNVIP neurons control specific phases of sleep and orchestrate the central extended amygdalas role in risk assessment and defensive responses. HIGHLIGHTSO_LIDRNVIP neurons form a subset of DRNDA neurons in mice and non-human primates. C_LIO_LIDRNVIP receive inputs from Protein Kinase C delta (PKC-{delta}) neurons in the ovBNST and CeA and project back to both. C_LIO_LIBy releasing glutamate, DRNVIP neurons regulate PKC-{delta} neuron excitability in the ovBNST and CeA. C_LIO_LIAblating DRNVIP neurons increases BNST and CeA activity, disrupts active-phase sleep architecture, and impairs threat responses. C_LI IN BRIEFDRNVIP neurons, a key subset of DRNDA neurons in mice and primates, are strategically positioned to influence the central extended amygdala via feedback loops. They regulate PKC-{delta} neuron excitability in the ovBNST and CeA through glutamate release, with their ablation heightening activity in these regions and altering active-phase sleep architecture, risk assessment and defensive behaviors.

neuroscience↗

bioRxiv2025

Protein corona formed on lipid nanoparticles compromises delivery efficiency of mRNA cargo

Lipid nanoparticles (LNPs) are the most clinically advanced nonviral RNA-delivery vehicles, though challenges remain in fully understanding how LNPs interact with biological systems. In vivo, proteins form an associated corona on LNPs that redefines their physicochemical properties and influences delivery outcomes. Despite its importance, the LNP protein corona is challenging to study owing to the technical difficulty of selectively recovering soft nanoparticles from biological samples. Herein, we developed a quantitative, label-free mass spectrometry-based proteomics approach to characterize the protein corona on LNPs. Critically, this protein corona isolation workflow avoids artifacts introduced by the presence of endogenous nanoparticles in human biofluids. We applied continuous density gradient ultracentrifugation for protein-LNP complex isolation, with mass spectrometry for protein identification normalized to protein composition in the biofluid alone. With this approach, we quantify proteins consistently enriched in the LNP corona including vitronectin, C-reactive protein, and alpha-2-macroglobulin. We explore the impact of these corona proteins on cell uptake and mRNA expression in HepG2 human liver cells, and find that, surprisingly, increased levels of cell uptake do not correlate with increased mRNA expression in part likely due to protein corona-induced lysosomal trafficking of LNPs. Our results underscore the need to consider the protein corona in the design of LNP-based therapeutics. Abstract Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=58 SRC="FIGDIR/small/633942v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@2fef29org.highwire.dtl.DTLVardef@fe7613org.highwire.dtl.DTLVardef@1f9de01org.highwire.dtl.DTLVardef@15e5237_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and vesicular GABA transporter

BackgroundAttention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome influenced by both genetic and environmental factors. While genetic studies have highlighted catecholamine dysfunction, emerging epidemiological evidence suggest neuroinflammation as a significant trigger. However, understanding the relative contributions of these alterations to ADHD symptomatology remains elusive. MethodThis study employed 93 female Swiss mice of the ADHD dopamine deficit model. Dopaminergic lesions were induced via 6-hydroxidopamine (6-OHDA) injection on postnatal day 5. The impact of these lesions during development was examined by comparing young and adult mice (at postnatal day 21 and 90, respectively). We sought to mitigate adult symptoms through abscisic acid (ABA) administration during two-months. Postmortem analyses encompassed the evaluation of neuroinflammation (microglia morphology, NLRP3 inflammasome activation, cytokine expression) and excitatory/inhibitory (E/I) ratio in specific brain regions. ResultsNeonatal dopaminergic lesions elicited hyperactivity, impulsivity, hypersensitivity increased social interaction in both one-month and three-month females and induced impaired memory in three-month mice. ABA exposure significantly ameliorated hyperactivity, impulsivity, anxiety, hypersensitivity, and social interaction alterations, but not cognitive impairment. In the anterior cingulate cortex (ACC) of one-month mice dopamine-deficit elevated IL-1{beta} and TNF expression and reduced Arg1 mRNA levels, along with E/I imbalance. ABA intervention restored microglia morphology, IL-1{beta}, Arg1 expression and enhanced vGAT levels. ConclusionsThis study strongly suggest that dopamine deficit induced alteration of microglia and E/I ratio underling distinct ADHD symptoms. Reinstating healthy microglia by anti-inflammatory agents in specific areas emerges as a promising strategy for managing ADHD.

neuroscience↗

bioRxiv2024

Near infrared fluorescent nanosensors for high spatiotemporal oxytocin imaging

Oxytocin is a neuropeptide involved in regulating social and emotional behavior. Current techniques for oxytocin imaging are generally limited in spatial and temporal resolution, real-time imaging capacity, selectivity for oxytocin over vasopressin, and application in young and non-model organisms. To address these issues, we developed a method to evolve purely synthetic molecular recognition for oxytocin on the surface of near-infrared fluorescent single-walled carbon nanotubes (SWCNT) using single-stranded DNA (ssDNA). The best-performing nanosensor nIROT-SELEC reversibly undergoes up to a 172% fluorescence increase in response to oxytocin with micromolar dissociation, nanomolar limit of detection, and and high selectivity over oxytocin analogs, receptor agonists and antagonists, and co-released neurochemicals. We next demonstrated the versatility of nIROT-SELEC by performing live imaging of synaptic evoked oxytocin released in acute brain slices of mice and prairie voles. Our method for high throughput evolution of neuropeptide nanosensors holds promise to enable synaptic scale visualization of neuropeptide signaling in the brain cross different species and developmental stages, to advance the study of neurochemical signaling for its role in both health and disease.

neuroscience↗

bioRxiv2023

Unravelling the neural dynamics of hypnotic susceptibility: Aperiodic neural activity as a central feature of hypnosis

How well a person responds to hypnosis is a stable trait, which exhibits considerable inter-individual diversity across the general population. Yet, its neural underpinning remains elusive. Here, we address this gap by combining EEG data, multivariate statistics, and machine learning in order to identify brain patterns that differentiate between individuals high and low in susceptibility to hypnosis. In particular, we computed the periodic and aperiodic components of the EEG power spectrum, as well as graph theoretical measures derived from functional connectivity, from data acquired at rest (pre-induction) and under hypnosis (post-induction). We found that the 1/f slope of the EEG spectrum at rest was the best predictor of hypnotic susceptibility. Our findings support the idea that hypnotic susceptibility is a trait linked to the balance of cortical excitation and inhibition at baseline and offers novel perspectives on the neural foundations of hypnotic susceptibility. Future work can explore the contribution of background 1/f activity as a novel target to distinguish the responsiveness of individuals to hypnosis at baseline in the clinic. Significance StatementHypnotic phenomena reflect the ability to alter ones subjective experiences based on targeted verbal suggestions. This ability varies greatly in the population. The brain correlates to explain this variability remain elusive. Addressing this gap, our study employs machine learning to predict hypnotic susceptibility. By recording electroencephalography (EEG) before and after a hypnotic induction and analyzing diverse neurophysiological features, we were able to determine that several features differentiate between high and low hypnotic susceptible individuals both at baseline and during hypnosis. Our analysis revealed that the paramount discriminative feature is non-oscillatory EEG activity before the induction--a new finding in the field. This outcome aligns with the idea that hypnotic susceptibility represents a latent trait observable through a plain five-minutes resting-state EEG.

neuroscience↗

bioRxiv2022

Differential and overlapping effects between exogenous and endogenous attention shape perceptual facilitation during visual processing

Visuospatial attention is not a monolithic process and can be divided into different functional systems. In this framework, exogenous attention reflects the involuntary orienting of attention resources following a salient event, whereas endogenous attention corresponds to voluntary orienting based on the goals and intentions of individuals. Previous work shows that these attention processes map onto distinct functional systems, yet evidence suggests that they are not fully independent. In the current work, we investigated the differential and overlapping effects of exogenous and endogenous attention on visual processing. We combined spatial cueing of visuospatial attention, electroencephalography (EEG), and multivariate pattern analysis (MVPA) to examine where and when the effects of exogenous and endogenous attention were maximally different and maximally similar. Critically, MVPA provided new insights by examining whether classifiers trained to decode the cueing effect for one attention process (e.g., exogenous attention) can successfully decode the cueing effect for the other attention process (e.g., endogenous attention). These analyses uncovered differential and overlapping effects between exogenous and endogenous attention. Next, we combined principal component analyses, single-trial event-related potentials, and mediation analysis to determine whether these effects facilitate perception, as indexed by the behavioral spatial cueing effects of exogenous and endogenous attention. This approach revealed that three EEG components shape the cueing effects of exogenous and endogenous attention at various times after target onset. Altogether, our study provides a comprehensive account about how overlapping and differential processes of endogenous and exogenous relate to perceptual facilitation in the context of visuospatial attention. Significance StatementTop-down and bottom-up attention represent separate functional systems in the brain. Previous research suggests, however, that they are not fully independent, and can interfere with each other. In the present study, the authors use machine learning techniques and recordings of brain activity to investigate differences and similarities between top-down and bottom-up attention during the visual processing of stimuli. This approach allowed them to explore how top-down and bottom-up attention processes facilitate perception. Their results show that top-down and bottom-up attention operate differently as early as 100ms after the onset of a target. In contrast, they operate similarly 200ms after the target onset. Most importantly, these effects are directly related to the participants perceptual behavior. In sum, our study shows that top-down and bottom-up attention support the perception of stimuli through overlapping and distinct spatio-temporal brain patterns.

neuroscience↗

bioRxiv2022

Exogenous attention interferes with endogenous attention processing via lateralized alpha power

Current theories of attention differentiate exogenous (bottom-up) from endogenous (top-down) orienting of visuospatial attention. While both forms of attentional processing engage different processes, endogenous and exogenous attention are thought to share processing resources, as shown by recent empirical evidence of their functional interactions. Here, we aim to uncover the neurobiological basis of how salient events that drive exogenous attention disrupts endogenous attention processes. We hypothesize that interference from exogenous attention over endogenous attention involves alpha-band activity, a neural marker of visuospatial attention. To test this hypothesis, we contrast the effects of endogenous attention across two experimental conditions: a single cueing condition where endogenous attention is engaged in isolation, and a double cueing condition where endogenous attention is concurrently engaged with exogenous attention. Our results are consistent with previous work and show that the concurrent engagement of exogenous attention interferes with endogenous attention processes. Importantly, we evaluate our main hypothesis using a moderated mediation model. We found that changes in alpha-band activity mediate the relationship between endogenous attention and its benefits on task performance, and that the interference of exogenous attention on endogenous attention occurs via the moderation of this indirect effect. Altogether, our results substantiate a model of attention, whereby top-down and bottom-up attentional processes compete for shared neurophysiological resources. This model accounts for the observed patterns of interference between exogenous and endogenous attention. Significance StatementScientists differentiate top-down and bottom-up visuospatial attention processes. While bottom-up attention is rapidly engaged by emerging demands from the environment, top-down attention reflects slow voluntary shifts of attention. Several lines of research substantiate the idea that top-down and bottom-up attentional processes involve distinct brain systems. An increasing number of studies, however, argue that both attention systems share brain processing resources. The current study examines how salient visual events that engage bottom-up processes interfere with top-down processes. Using neurophysiological recordings and multivariate pattern classification techniques, the researchers show that both top-down and bottom-up attention processes do share brain resources expressed via alpha-band neurophysiological activity (8-12 Hz). The results further demonstrate that the interference patterns observed over brain activity in the alpha-band between both attention systems explains, in part, the interference between top-down and bottom-up attention at the behavioural level. The authors conclude by proposing a model of visuospatial attention whereby the dynamics between both attention systems are determined by their competition for limited brain processing resources.

neuroscience↗

bioRxiv2022

Targeting neuroinflammation with Abscisic Acid reducespain sensitivity in females and hyperactivity in males of an ADHD mice model

AimsAttention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome characterized by dopaminergic dysfunction. In this study, we aimed to demonstrate the link between dopaminergic deficit and neuroinflammation underlying ADHD symptoms. Subjects and TreatmentWe used a validated ADHD mice model, that involves perinatal 6-OHDA lesion. Animals were treated with 20mg/L (drinking water) of Abscisic acid (ABA) for one month. We tested behaviour (learning and memory, anxiety, social interactions, and pain) in both females and male mice, in all eight groups (control and lesioned, with/without ABA). Postmortem, we analyzed microglia morphology and Ape1 expression in specific brain areas related to the descending pain inhibitory pathway. ResultsIn females, dopaminergic deficit increased pain sensitivity, but not hyperactivity, in contrast to males. This behaviour was associated with inflammatory microglia and lower Ape1 levels in the anterior cingulate cortex (ACC) and posterior insula cortex (IC). ABA treatment reduced inflammation and alleviated pain. In males, ABA reduced hyperactivity, but had no significant effect on inflammation. ConclusionsThis is the first study proving a sex-dependent association between dopamine dysfunction and inflammation in specific brain areas, leading to different behavior outcomes in a mouse model of ADHD. These findings provide new clues for potential treatments.

neuroscience↗

bioRxiv2022

Evidence for shared resources in visuospatial attention: Endogenous attention misleads the decoding of exogenous attention in alpha rhythms

Prevailing accounts of visuospatial attention differentiate exogenous (involuntary shifts) from endogenous (voluntary control) orienting of attention. While these two forms of attentional processes are functionally separable, their interactions have been at the center of ongoing debates for more than two decades. One hypothesis is that exogenous and endogenous attention interfere because they share processing resources. Here, we confirm that endogenous attention alters exogenous attention processing, and examine the role of alpha-band neurophysiological activity in such interference events. We contrast the effects of exogenous attention across two experimental conditions: a single-cueing condition where exogenous attention is engaged alone, and a double-cueing condition where exogenous attention is concurrently engaged with endogenous attention. Our results show that the engagement of endogenous attention alters the emergence of exogenous attention across cue-related and target-related brain processes. Importantly, we also report that classifiers trained to decode exogenous attention from the power and phase of alpha-band brain activity in the single-cueing condition fail to do so in the doublecueing condition, where endogenous attention is also engaged. Taken together, our observations challenge the idea that exogenous attention operates independently from top-down processes and demonstrate that both forms of attention orienting engage shared brain processes, which constrain their interactions. Significance StatementVisuospatial attention is often dichotomized into top-down and bottom-up components: Top-down attention reflects slow voluntary shifts of attention orienting, while bottom-up attention is recruited by emerging demands from the environment. A large body of previous findings support the view that these two forms of attention orienting are functionally separable, with some interactions. The current study examines such interactions between top-down and bottom-up attention. Using electroencephalography (EEG) and multivariate pattern classification techniques, the researchers show that top-down attention interferes with the brain activity patterns of bottom-up attention. Moreover, machine learning classifiers trained to detect bottom-up attention based on brain activity in the alpha band (8-12 Hz), a marker of visuospatial attention, fail systematically when top-down attention is also engaged. The authors therefore conclude that both forms of visuospatial orienting are supported by overlapping processes that share brain resources.

neuroscience↗

bioRxiv2022

Surface motility favors co-dependent interaction between Pseudomonas aeruginosa and Burkholderia cenocepacia

Interactions between different bacterial species shape bacterial communities and their environments. The opportunistic pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia both can colonize the lungs of individuals affected by cystic fibrosis. Using the social surface behavior called swarming motility as a study model of interactions, we noticed intricate interactions between B. cenocepacia K56-2 and P. aeruginosa PA14. While strain K56-2 does not swarm under P. aeruginosa favorable swarming conditions, co-inoculation with a non-motile PA14 flagellum-less {Delta}fliC mutant restored spreading for both strains. We show that P. aeruginosa provides the wetting agent rhamnolipids allowing K56-2 to perform swarming motility, while aflagellated PA14 seems able to < > along with K56-2 cells in the swarming colony. ImportancePseudomonas aeruginosa and Burkholderia cenocepacia are important opportunistic pathogens often found together in the airways of persons with cystic fibrosis. Laboratory co-culture of both species often ends with one taking over the other. We used a surface motility assay to study the social interactions between population of these bacterial species. Under our conditions, B. cenocepacia cannot swarm without supplementation of the wetting agent produced by P. aeruginosa. In a mixed colony of both species, an aflagellated mutant of P. aeruginosa provides the necessary wetting agent to B. cenocepacia, allowing both bacteria to swarm and colonize a surface. We highlight this peculiar interaction where both bacteria set aside their antagonistic tendencies to cooperate.

microbiology↗

bioRxiv2022

Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior

In threatening situations, animals exhibit a broad range of behavioral and autonomic responses. As such, a crucial adaptive response is the inhibition of pain, which facilitates relevant defensive behaviors that promote survival. Whereas the structures and mechanisms involved in fear and pain behaviors are well documented, little is known about the precise neuronal mechanisms mediating the emotional regulation of endogenous pain-suppression. Here, we used a combination of behavioral, anatomical, optogenetic, and electrophysiological approaches to investigate, in male mice, the role of somatostatin-expressing cells in the ventrolateral periaqueductal gray matter (SST+ vlPAG cells) in the control of analgesia induced during defensive states. Our data indicate that optogenetic inhibition of SST+ vlPAG cells promotes analgesia irrespective of animal defensive state. In contrast, optogenetic activation of long-range SST+ vlPAG cells that project to the rostral ventromedial medulla (RVM) abolishes the analgesia mediated by fear behavior. Together, these results identify a novel circuit mechanism composed of long-range SST+ vlPAG cells projecting to the RVM that regulate analgesia elicited during defensive states.

neuroscience↗