bluuebunny/crossref_metadata_2025_split huggingface dataset:
hMT+ Activity Predicts the Effect Of Spatial Attention On Surround Suppression
Authors: Kiniklioglu Merve , Boyaci Huseyin 
Published: October 2024

AbstractSurround suppression refers to the decrease in behavioral sensitivity and neural response to a central stimulus due to the presence of surrounding stimuli. Several aspects of surround suppression in human motion perception have been studied in detail, including its atypicality in some clinical populations. However, how the extent of spatial attention affects the strength of surround suppression has not been systematically studied before. To address this question, we presented human participants with ‘center’ and ‘surround’ drifting gratings and sought to find whether attending only to the center (‘narrow attention’) versus both to the center and surround (‘wide attention’) modulates the suppression strength in motion processing. Using psychophysics and functional magnetic resonance imaging (fMRI), we measured motion direction discrimination thresholds and cortical activity in the primary visual cortex (V1) and middle temporal complex (hMT+). We found increased perceptual thresholds and, thus, stronger surround suppression under the wide attention condition. We also found that the pattern of hMT+ activity was consistent with the behavioral results. Furthermore, a mathematical model that combines spatial attention and divisive normalization was able to explain the pattern in the behavioral and fMRI results. These findings provide a deeper understanding of how attention affects center-surround interactions and suggest possible neural mechanisms with relevance to both basic and clinical vision science.Significance StatementOur sensitivity to the drift direction of a grating decreases when it is surrounded by an iso-oriented high-contrast surround. Here, we report the first systematic neuroimaging study on how the extent of spatial attention modulates the strength of this ‘surround suppression’. We found that the strength of surround suppression increases as the extent of spatial attention increases, and, pointing to its critical role, hMT+ activity predicts these results. Furthermore, a mathematical model combining spatial interactions and attention could explain the results. In addition to their relevance to basic vision science, these findings have clinical implications because they suggest that the atypical surround suppression observed in some populations could be related to abnormal spatial attention mechanisms.
A sensory approach to turbidity: How sources and levels shape aquatic light environments and fish visual ecology
Authors: Garcia Anna , Sibeaux Adelaide , Burt de Perera Theresa , Newport Cait 
Published: October 2024

AbstractTurbidity is a ubiquitous source of sensory pollution that is likely to impact the appearance of the visual stimuli that animals rely on for survival and reproduction. Understanding how different turbidity sources impact the appearance of the ambient light environment is the foundational first step towards predicting whether and how animals will cope with the global increases in the severity and frequency of high turbidity events caused by anthropogenic disturbance. Here, we measured how four common turbidity sources (algae, bentonite, calcium carbonate, and kaolin), and variable turbidity levels, changed the appearance of the ambient light environment. We measured total number of photons (luminance), hue, chroma, and image contrast, and we evaluated the effect of each turbidity source and level on settling rate, pH, and KH. Both turbidity source and turbidity level impacted the appearance of the ambient light environment. With increasing turbidity level, calcium carbonate and kaolin increased luminance while algae decreased luminance, bentonite caused the greatest change in hue, and algae caused the greatest change in chroma. This demonstrates that the impacts of different turbidity sources on the ambient light environment are not uniform, giving a potential explanation for the discrepancies between studies on the effects of turbidity on fish behaviour. Consideration of the effect of specific turbidity sources on ambient light is crucial for the design of experiments that seek to investigate how changes in turbidity impact the perception of important visual information, which underpins the survival and reproductive success of aquatic organisms around the world.Summary StatementDifferent turbidity sources and levels uniquely affect aquatic light environments and fish visual perception, emphasizing the need for these factors when interpreting fish behaviour and the ecological consequences of turbidity.
Expectation generation and its effect on subsequent pain and visual perception
Authors: Botvinik-Nezer Rotem , Geuter Stephan , Lindquist Martin A. , Wager Tor D. 
Published: October 2024

AbstractBayesian accounts of perception, such as predictive processing, suggest that perceptions integrate expectations and sensory experience, and thus assimilate to expected values. Furthermore, more precise expectations should have stronger influences on perception. We tested these hypotheses in a paradigm that manipulates both the mean value and the precision of cues within-person. Forty-five participants observed cues–presented as ratings from 10 previous participants–with varying cue means, variances (precision), and skewness across trials. Participants reported expectations regarding the painfulness of thermal stimuli or the visual contrast of flickering checkerboards. Subsequently, similar cues were each followed by a visual or noxious thermal stimulus. While perceptions assimilated to expected values in both modalities, cues’ precision mainly affected visual ratings. Furthermore, behavioral and computational models revealed that expectations were biased towards extreme values in both modalities, and towards low-pain cues specifically. fMRI analysis revealed that the cues affected systems related to higher-level affective and cognitive processes–including assimilation to the cue mean in a neuromarker of endogenous contributions to pain and in the nucleus accumbens, and activity consistent with aversive prediction-error-like encoding in the periaqueductal gray during pain perception–but not systems related to early perceptual processing. Our findings suggest that predictive processing theories should be combined with mechanisms such as selective attention to better fit empirical findings, and that expectation generation and its perceptual effects are mostly modality-specific and operate on higher-level processes rather than early perception.
On the patterns of genetic intra-tumour heterogeneity before and after treatment
Authors: Stein Alexander , Werner Benjamin 
Published: October 2024

AbstractGenetic intra-tumour heterogeneity (gITH) is a universal property of all cancers. It emerges from the interplay of cell division, mutation accumulation and selection with important implications for the evolution of treatment resistance. Theoretical and data-driven approaches extensively studied gITH in ageing somatic tissues or cancers at detection. Yet, the expected patterns of gITH during and after treatment are less well understood. Here, we use stochastic birth-death processes to investigate the expected patterns of gITH across different treatment scenarios. We consider homogeneous treatment response with shrinking, growing and stable disease, and follow up investigating heterogeneous treatment response with sensitive and resistant cell types. We derive analytic expressions for the site frequency spectrum, the total mutational burden and the single-cell mutational burden distribution that we validate with computer simulations. We find that the SFS after homogeneous treatment response retains its characteristic power-law tail, while emergent resistant clones cause peaks corresponding to their sizes. The frequency of the largest resistant clone is subdominant and independent of the population size at detection, whereas the relative total number of resistant cells increases with detection size. Furthermore, the growth dynamics under treatment determine whether the total mutational burden is dominated by preexisting or newly acquired mutations, suggesting different possible treatment strategies.
Convergent depression of activity-dependent bulk endocytosis in rodent models of autism spectrum disorders
Authors: Bonnycastle Katherine , Kind Peter C. , Cousin Michael A. 
Published: October 2024

AbstractThe key pathological mechanisms underlying autism spectrum disorders (ASDs) remain relatively undetermined, potentially due to the heterogenous nature of the condition. Targeted studies of a series of monogenic ASDs have revealed postsynaptic dysfunction as a central conserved mechanism. Presynaptic dysfunction is emerging as an additional disease locus in neurodevelopmental disorders, however it is unclear whether this dysfunction drives ASDs or is an adaptation to the altered brain microenvironment. To determine this, we performed a high content analysis of key stages of the synaptic vesicle lifecycle in a series of preclinical models of monogenic ASDs. These models were specifically selected to have perturbations in a diverse palette of genes that were expressed either at the pre- or post-synapse. However, all models displayed a common trait of hyperexcitability. We determined that SV fusion events and SV cargo trafficking were unaffected in all models investigated. However, a key convergent phenotype was revealed, a depression in activity-dependent bulk endocytosis (ADBE). This suggests that the depression in ADBE is a homeostatic mechanism to correct hyperexcitability in the ASD brain.
Male is the default sex: functional significance of the sex determination cascade in horned dung beetles
Authors: Mitchell London C. , Moczek Armin P. , Nadolski Erica M. 
Published: October 2024

AbstractSex-specific trait expression represents a striking dimension of morphological variation within and across species. The mechanisms instructing sex-specific organ development have been well studied in a small number of insect model systems, suggesting striking conservation in some parts of the somatic sex determination pathway while hinting at possible evolutionary lability in others. However, further resolution of this phenomenon necessitates additional taxon sampling, particularly in groups in which sexual dimorphisms have undergone significant elaboration and diversification. Here, we functionally investigate the somatic sex determination pathway in the gazelle dung beetleDigitonthophagus gazella, an emerging model system in the study of the development and evolution of sexual dimorphisms. We find that RNA interference (RNAi) targetingtransformer1 (tra1)caused chromosomal females to develop morphological traits largely indistinguishable from those normally only observed in males, and thattra1RNAiis sufficient to induce splicing of the normally male-specific isoform ofdoublesexin chromosomal females, while leaving males unaffected. Further,intersexRNAiwas found to phenocopy previously described RNAi phenotypes ofdoublesexin female but not male beetles. These findings match predictions derived from models of the sex determination cascade as developed largely through studies inDrosophila melanogaster. In contrast,transformer2RNAiresulted in larval mortality and was not sufficient to affectdoublesexsplicing, whereas RNAi targetingSex-lethaland two putative orthologs ofhermaphroditeyielded no obvious phenotypic modifications in either males or females, raising the possibility that the function of a subset of sex determination genes may be derived in Diptera and thus non-representative of their roles in other holometabolous orders. Our results help illuminate how the differential evolutionary lability of the somatic sex determination pathway has contributed to the extraordinary morphological diversification of sex-specific trait expression found in nature.
Gasdermin D is activated but does not drive neurodegeneration in SOD1G93Amodel of ALS: Implications for targeting pyroptosis
Authors: Gunner Georgia , Basu Himanish , Lu Yueting , Bergstresser Matthew , Neel Dylan , Choi So Yoen , Chiu Isaac M. 
Published: October 2024

AbstractAmyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, microgliosis, and neuroinflammation. While pyroptosis, an inflammatory form of programmed cell death, has been implicated in ALS, the specific role of Gasdermin D (GSDMD) – the primary executioner of pyroptosis – remains unexplored. In this study, we examined the function of GSDMD in the well-established SOD1G93Amouse model of ALS. Our results showed robust GSDMD activation in the spinal cords of SOD1G93Aanimals across two strain backgrounds, with elevated expression in Iba1+ microglia. To explore its role in disease progression, we bred B6.SOD1G93Amice onto a GSDMD-deficient background. In comparing SOD1G93A;Gsdmd+/+ and SOD1G93A;Gsdmd−/− mice, we found thatGsdmdloss did not affect disease onset, weight loss, or grip strength decline in either male or female animals. Notably, GSDMD deficiency resulted in a modest but statistically significant increase in mortality in SOD1G93Amice. Moreover, GSDMD absence had minimal impact on astrogliosis, microgliosis and motor neuron loss. These findings show that while GSDMD is activated in the ALS mouse model, its loss does not mitigate key ALS behavioral phenotypes, gliosis or motor neuron loss. This study provides insights into the potential therapeutic relevance of targeting pyroptosis and inflammatory pathways in ALS.
Contribution of rat insular cortex to stimulus-guided action
Authors: Tensaouti Yacine , Morel Louis , Parkes Shauna L. 
Published: October 2024

ABSTRACTAnticipating rewards is fundamental for decision-making. Animals often use cues to assess reward availability and to make predictions about future outcomes. The gustatory region of the insular cortex (IC), the so-called gustatory cortex, has a well-established role in the representation of predictive cues, such that IC neurons encode both a general form of outcome expectation as well as anticipatory outcome-specific knowledge. Here, we used Pavlovian-instrumental transfer (PIT) in male rats to assess if the IC is also required for predictive cues to exert both a general and specific influence over instrumental actions. Chemogenetic inhibition of IC abolished the ability of a reward-predictive stimulus to energize instrumental responding for reward. This deficit in general transfer was evident whether the same or different outcomes were used in the Pavlovian and instrumental conditioning phases. We observed a similar deficit in specific PIT, such that rats with IC inhibition failed to use a reward-predictive stimulus to guide choice toward actions that deliver the same food reward. Finally, we show that rats with IC inhibition also fail to show outcome-selective reinstatement. Together, these data suggest a crucial role for IC in the representation of appetitive outcomes, and particularly in using this representation to guide instrumental action.SIGNIFICANCE STATEMENTAnimals frequently use cues to infer the availability of rewards and to make predictions about future outcomes. The influence of these predictive cues on behaviour can be studied using Pavlovian-instrumental transfer (PIT), in which Pavlovian outcome expectancies can elevate (general PIT) or selectively guide (specific PIT) instrumental actions. In the current study, we show that chemogenetic inhibition of the gustatory region of insular cortex (IC) abolishes both general and specific transfer, as well as the selectivity of outcome-induced reinstatement. These results demonstrate a critical role for the IC in the representation of appetitive outcomes and significantly contribute to a broader understanding of the cortical bases of PIT.
Rapid, interpretable, data-driven models of neural dynamics using Recurrent Mechanistic Models
Authors: Burghi Thiago B. , Ivanova Maria , Morozova Ekaterina , Wang Huaxinyu , Marder Eve , O’Leary Timothy 
Published: October 2024

Obtaining predictive models of a neural system is notoriously challenging. Detailed models suffer from excess model complexity and are difficult to fit efficiently. Simplified models must negotiate a tradeoff between tractability, predictive power and ease of interpretation. We present a new modelling paradigm for estimating predictive mechanistic-like models of neurons and small circuits that navigates these issues using methods from systems theory. The key insight is that membrane currents can be modelled using two scalable system components optimized for learning: linear state space models, and nonlinear artificial neural networks (ANNs). Combining these components, we construct two types of membrane currents: lumped currents, which are flexible, and data-driven conductance-based currents, which are interpretable. The resulting class of models — which we call Recurrent Mechanistic Models (RMMs) — can be trained in a matter of seconds to minutes on intracellular recordings during an electrophysiology experiment, representing a step change in performance over previous approaches. As a proof-of-principle, we use RMMs to learn the dynamics of two groups of neurons, and their synaptic connections, in the Stomatogastric Ganglion (STG), a well-known central pattern generator. We show that RMMs are efficiently trained using teacher forcing and multiple shooting. Due to their reliability, efficiency and interpretability, RMMs enable qualitatively new kinds of experiments using predictive models in closed-loop neurophysiology and online estimation of neural properties in living preparations.Significance StatementOur ability to understand the nervous system has been hindered by the difficulty of constructing good predictive models of neurons and circuits. This difficulty persists despite vast accumulated knowledge of how the basic components of the nervous system work, marking a gap in our ability to explain neural dynamics in terms of underlying mechanisms. This work describes a new data-driven modelling approach for neurons and small circuits that combines predictive power with mechanistic interpretation.
Prefrontal representations of retrospective spatial working memory in a rodent radial maze task
Authors: Taliaferro Joshua Paul , Posani Lorenzo , Greenwald Julia , Lim Sean , McGowan Josephine Cecelia , Pekarskaya Elizabeth , Lacefield Clay , Fusi Stefano , Kellendonk Christoph 
Published: October 2024

AbstractWorking memory is the cognitive capacity for temporarily holding information in mind for processing or use. It has been theorized to depend upon executive and mnemonic subcomponents, although the contextual mapping of these subcomponents is not complete. Perturbations of prefrontal cortex (PFC) delay activity disrupt spatial working memory performance in rodent tasks. However, recordings of unperturbed PFC delay activity do not consistently contain mnemonic representations of spatial information in these tasks, calling into question the role that mnemonic PFC representations play in freely-moving spatial working memory. We hypothesized that increasing task complexity might increase the likelihood of mnemonic PFC representation emergence. We therefore used an automated eight-arm radial maze to implement a novel match-to-sample rodent spatial working memory task with seven options on each trial, and recorded calcium activity in PFC neurons during task performance. We found that the delay-phase activity of PFC neurons indeed contained mnemonic representations of spatial information at the population level. These representations were retrospective rather than prospective, and—surprisingly—were more evident on error trials. Together with previous results, these observations suggest that in freely-moving spatial working memory tasks, PFC mnemonic representations emerge to empower deviation from a routine behavioral strategy.Significance StatementPrefrontal cortex (PFC) activity is necessary for optimal performance of freely-moving spatial working memory tasks in rodents. Despite this, PFC representations of retrospective actions or stimuli—one quintessential working memory hallmark—are only variably observed during task delays, complicating our understanding of the PFC’s role in spatial working memory. Here, we examine cellular-resolution PFC activity in a high-optionality match-to-sample radial maze task and find retrospective delay representations. Strikingly, these delay representations are more evident in error trials. This suggests that in the freely-moving context, explicit PFC representations of retrospective information support deviations from an entrained behavioral strategy, rather than equally supporting all spatial working memory-based behavior.
Orthrus: Towards Evolutionary and Functional RNA Foundation Models
Authors: Fradkin Philip , Shi Ruian , Isaev Keren , Frey Brendan J. , Morris Quaid , Lee Leo J. , Wang Bo 
Published: October 2024

AbstractIn the face of rapidly accumulating genomic data, our ability to accurately pre-dict key mature RNA properties that underlie transcript function and regulation remains limited. Pre-trained genomic foundation models offer an avenue to adapt learned RNA representations to biological prediction tasks. However, existing genomic foundation models are trained using strategies borrowed from textual or visual domains that do not leverage biological domain knowledge. Here, we intro-duce Orthrus, a Mamba-based mature RNA foundation model pre-trained using a novel self-supervised contrastive learning objective with biological augmentations. Orthrus is trained by maximizing embedding similarity between curated pairs of RNA transcripts, where pairs are formed from splice isoforms of 10 model organ-isms and transcripts from orthologous genes in 400+ mammalian species from the Zoonomia Project. This training objective results in a latent representation that clusters RNA sequences with functional and evolutionary similarities. We find that the generalized mature RNA isoform representations learned by Orthrus significantly outperform existing genomic foundation models on five mRNA prop-erty prediction tasks, and requires only a fraction of fine-tuning data to do so. Finally, we show that Orthrus is capable of capturing divergent biological function of individual transcript isoforms.