eNeuro最新文献

Visual information emerging from the extrafoveal locations is important for visual search, saccadic eye movement control, and spatial attention allocation. Our everyday sensory experience with visual object categories varies across different parts of the visual field which may result in location-contingent variations in visual object recognition. We used a body, animal body, and chair two-forced choice object category recognition task to investigate this possibility. Animal body and chair images with various levels of visual ambiguity were presented at the fovea and different extrafoveal locations across the vertical and horizontal meridians. We found heterogeneous body and chair category recognition across the visual field. Specifically, while the recognition performance of the body and chair presented at the fovea were similar, it varied across different extrafoveal locations. The largest difference was observed when the body and chair images were presented at the lower-left and upper-right visual fields, respectively. The lower/upper visual field bias of the body/chair recognition was particularly observed in low/high stimulus visual signals. Finally, when subjects' performances were adjusted for a potential location-contingent decision bias in category recognition by subtracting the category detection in full noise condition, location-dependent category recognition was observed only for the body category. These results suggest heterogeneous body recognition bias across the visual field potentially due to more frequent exposure of the lower visual field to body stimuli.Significance Statement Our study reveals that visual object recognition exhibits notable variations across different visual field regions, with a pronounced bias in recognizing body images in the lower visual field. This heterogeneity in recognition performance suggests that the frequent exposure of certain visual field areas to specific object categories, such as bodies, influences our visual processing abilities. These findings highlight the importance of considering spatial attention and saccadic eye movements in understanding visual object recognition and have potential implications for designing more effective visual information displays and interfaces.

Acute ischemic stroke (AIS) is a dangerous neurological disease associated with an imbalance in Th17/Treg cells and abnormal activation of the Wnt/β-catenin signaling pathway. This study aims to investigate whether inhibition of miR-155 can activate the Wnt/β-catenin signaling pathway to improve Th17/Treg imbalance and provide neuroprotective effects against stroke. We employed a multi-level experimental design. Firstly, we analyzed the differential gene expression between the miR-155 antagomir-treated group and the control group using high-throughput sequencing to identify potential target genes. Subsequently, we conducted functional and pathway enrichment analysis of the differentially expressed genes using bioinformatics tools. Next, we performed in vivo animal experiments using a mouse model to validate the impact of miR-155 antagomir treatment on the Wnt/β-catenin signaling pathway and improvement of Th17/Treg cell ratios. Lastly, we conducted in vitro cell experiments to validate our findings further. High-throughput sequencing results showed significant differential expression between the miR-155 antagomir-treated group and the control group (BioProject: PRJNA1152758, SRA IDs: SRR30410532, SRR30410531, SRR30410530 for the disease group; SRR30410529, SRR30410528, SRR30410527 for the control group). Bioinformatics analysis revealed potential target genes associated with the Wnt/β-catenin signaling pathway and Th17/Treg cell imbalance. In vitro experiments demonstrated that miR-155 antagomir treatment significantly activated the Wnt/β-catenin signaling pathway and improved Th17/Treg cell ratios. In vivo, animal experiment results indicated that miR-155 antagomir treatment exhibited significant neuroprotective effects against AIS. This study demonstrates that miR-155 antagomir can improve Th17/Treg cell imbalance by activating the Wnt/β-catenin signaling pathway and exhibiting neuroprotective effects against AIS in a mouse model. These findings provide crucial support for miR-155 as a potential therapeutic strategy for stroke and lay the foundation for further research.Significance Statement This study identifies miR-155 as a pivotal regulator of the Th17/Treg cell balance and Wnt/β-catenin signaling pathway in AIS. By inhibiting miR-155, we demonstrate the potential to enhance neuroprotection and modulate immune responses, offering a promising therapeutic avenue for stroke management. These findings contribute to the growing understanding of molecular mechanisms in stroke and provide a foundation for developing miR-155-targeted therapies.

To develop reparative therapies for neurological disorders like multiple sclerosis (MS), we need to better understand the physiology of loss and replacement of oligodendrocytes, the cells that make myelin and are the target of damage in MS. In vivo two-photon fluorescence microscopy allows direct visualization of oligodendrocytes in the intact brain of transgenic mouse models, promising a deeper understanding of the longitudinal dynamics of replacing oligodendrocytes after damage. However, the task of tracking the fate of individual oligodendrocytes requires extensive effort for manual annotation and is especially challenging in three-dimensional images. While several models exist for annotating cells in two-dimensional images, few models exist to annotate cells in three-dimensional images and even fewer are designed for tracking cells in longitudinal imaging. Notably, existing options often come with a substantial financial investment, being predominantly commercial or confined to proprietary software. Furthermore, the complexity of processes and myelin formed by individual oligodendrocytes can result in the failure of algorithms that are specifically designed for tracking cell bodies alone. Here, we propose a fast, free, consistent, and unsupervised beta-mixture oligodendrocyte segmentation system (FAST) that is written in open-source software, and can segment and track oligodendrocytes in three-dimensional images over time with minimal human input. We showed that the FAST model can segment and track oligodendrocytes similarly to a blinded human observer. Although FAST was developed to apply to our studies on oligodendrocytes, we anticipate that it can be modified to study four-dimensional in vivo data of any brain cell with associated complex processes.Significance Statement We have developed "FAST: Fast, free, consistent, and unsupervised oligodendrocyte segmentation and tracking system" to solve our challenge of quantification of four-dimensional data acquired from longitudinal in vivo imaging. Although it was developed for oligodendrocytes, we will make the code entirely open source and user-friendly, and expect that it will be useful for segmentation for any cell body from a complex cell amenable to longitudinal in vivo imaging.

The full complement of ion channels which influence insect auditory mechanotransduction and the mechanisms by which their influence is exerted remain unclear. Shal (K_v4), a Shaker family member encoding voltage-gated potassium channels in Drosophila melanogaster, has been shown to localize to dendrites in some neuron types, suggesting the potential role of Shal in Drosophila hearing, including mechanotransduction. A GFP trap was used to visualize the localization of the Shal channel in Johnston's organ neurons responsible for hearing in the antenna. Shal protein was localized strongly to the cell body and inner dendritic segment of sensory neurons. It was also detectable in the sensory cilium, suggesting its involvement not only in general auditory function but specifically in mechanotransduction. Electrophysiological recordings to assess neural responses to auditory stimuli in mutant Shal flies revealed significant decreases in auditory responses. Laser Doppler vibrometer recordings indicated abnormal antennal free fluctuation frequencies in mutant lines, indicating an effect on active antennal tuning, and thus active transduction mechanisms. This suggests that Shal participates in coordinating energy-dependent antennal movements in Drosophila that are essential for tuning the antenna to courtship song frequencies.

The brain attends to environmental rhythms by aligning the phase of internal oscillations. However, the factors underlying fluctuations in the strength of this phase entrainment remain largely unknown. In the present study we examined whether the strength of low-frequency EEG phase entrainment to rhythmic stimulus sequences varied with pupil size and posterior alpha-band power, thought to reflect arousal level and excitability of posterior cortical brain areas, respectively. We recorded pupil size and scalp EEG while participants carried out an intermodal selective attention task, in which they were instructed to attend to a rhythmic sequence of visual or auditory stimuli and ignore the other perceptual modality. As expected, intertrial phase coherence (ITC), a measure of entrainment strength, was larger for the task-relevant than for the task-irrelevant modality. Across the experiment, pupil size and posterior alpha power were strongly linked with each other. Interestingly, ITC tracked both variables: larger pupil size was associated with a selective increase in entrainment to the task-relevant stimulus sequence, whereas larger posterior alpha power was associated with a decrease in phase entrainment to both the task-relevant and task-irrelevant stimulus sequences. Exploratory analyses showed that a temporal relation between ITC and posterior alpha power emerged in the time periods around pupil maxima and pupil minima. These results indicate that endogenous sources contribute distinctly to the fluctuations of EEG phase entrainment.Significance statement Fluctuations in cortical state powerfully shape the perception of external stimuli. Understanding the physiological signatures of cortical state fluctuations is crucial to understand how the brain selectively attends and switches between internal and external content. Here we studied how two signatures of attentional state, pupil-linked arousal and power in the alpha band, shape the entrainment of brain activity to low-frequency rhythmic stimuli. Our results reveal common and dissociable influences of these signatures at slow time scales. Furthermore, measuring and including pupil size and posterior alpha power as covariates in statistical models can help increase statistical power in studies focusing on EEG phase entrainment. Our study provides new evidence on a direct influence of cortical state on the perception of rhythmic stimuli.

The use of supervised machine learning to approximate poses in video recordings allows for rapid and efficient analysis of complex behavioral profiles. Currently, there are limited protocols for automated analysis of operant self-administration behavior. We provide methodology to 1) obtain videos of training sessions via Raspberry Pi microcomputers or GoPros 2) obtain pose estimation data using the supervised machine learning software packages DeepLabCut (DLC) and Simple Behavioral Analysis (SimBA) with local high performance computer cluster, 3) comparison of standard MedPC lever response vs quadrant time data generated from pose estimation regions of interest and 4) generation of predictive behavioral classifiers. Overall, we demonstrate proof-of-concept to use pose estimation outputs from DLC to both generate quadrant time results and obtain behavioral classifiers from SimBA during operant training phases.Significance Statement Substance use disorders are comprised of complex behaviors that promote chronic relapse to drug-seeking and -taking. Rodent operant self-administration is commonly used as a preclinical tool to examine drug-taking, -seeking and craving behavior. We provide protocols to acquire videos of self-administration behavior and obtain pose estimation outputs and unique behavioral classifiers using the supervised learning softwares DeepLabCut and Simple Behavioral Analysis (SimBA).

Brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) are known to contribute to both protective and pronociceptive processes. However, their contribution to neuropathic pain after spinal cord injury (SCI) needs further investigation. In a recent study utilizing TrkB^F616A mice, it was shown that systemic pharmacogenetic inhibition of TrkB signaling with 1NM-PP1 (1NMP) immediately after SCI delayed the onset of pain hypersensitivity, implicating maladaptive TrkB signaling in pain after SCI. To examine potential neural mechanisms underlying the behavioral outcome, patch-clamp recording was performed in small-diameter dissociated thoracic (T) dorsal root ganglia (DRG) neurons to evaluate TrkB signaling in uninjured mice and after T10 contusion SCI. Bath-applied 7,8-dihydroxyflavone (7,8-DHF), a selective TrkB agonist, induced a robust inward current in neurons from uninjured mice, which was attenuated by 1NMP treatment. SCI also decreased 7,8-DHF-induced current while increasing the latency to its peak amplitude. Western blot revealed a concomitant decrease in TrkB expression in DRGs adjacent to the spinal lesion. Analyses of cellular and membrane properties showed that SCI increased neuronal excitability, evident by an increase in resting membrane potential and the number of spiking neurons. However, SCI did not increase spontaneous firing in DRG neurons. These results suggest that SCI induced changes in TrkB activation in DRG neurons even though these alterations are likely not contributing to pain hypersensitivity by nociceptor hyperexcitability. Overall, this reveals complex interactions involving TrkB signaling and provides an opportunity to investigate other, presumably peripheral, mechanisms by which TrkB contributes to pain hypersensitivity after SCI.

A comprehensive analysis of everyday sound perception can be achieved using Electroencephalography (EEG) with the concurrent acquisition of information about the environment. While extensive research has been dedicated to speech perception, the complexities of auditory perception within everyday environments, specifically the types of information and the key features to extract, remain less explored. Our study aims to systematically investigate the relevance of different feature categories: discrete sound-identity markers, general cognitive state information, and acoustic representations, including discrete sound onset, the envelope, and mel-spectrogram. Using continuous data analysis, we contrast different features in terms of their predictive power for unseen data and thus their distinct contributions to explaining neural data. For this, we analyse data from a complex audio-visual motor task using a naturalistic soundscape. The results demonstrated that the feature sets that explain the most neural variability were a combination of highly detailed acoustic features with a comprehensive description of specific sound onsets. Furthermore, it showed that established features can be applied to complex soundscapes. Crucially, the outcome hinged on excluding periods devoid of sound onsets in the analysis in the case of the discrete features. Our study highlights the importance to comprehensively describe the soundscape, using acoustic and nonacoustic aspects, to fully understand the dynamics of sound perception in complex situations. This approach can serve as a foundation for future studies aiming to investigate sound perception in natural settings.Significance Statement This study is an important step in our broader research endeavor, which aims to understand sound perception in everyday life. Although conducted in a stationary setting, this research provides foundational insights into necessary environmental information to obtain to understand concurrent neural responses. We delved into the analysis of various acoustic features, sound-identity labeling, and cognitive information, with the goal of refining neural models related to sound perception. Our findings particularly highlight the need for a thorough analysis and description of complex soundscapes. Our study provides key considerations for future research in sound perception across various contexts, from laboratory settings to mobile EEG technologies, and paves the way for investigations into more naturalistic environments, advancing the field of auditory neuroscience.

A unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons, and likely supports local neuronal maturation and emerging synaptogenesis. Microglia may alter neuronal growth following environmental perturbations such as stress. Using multiple measures in Rhesus Macaques, we found that microglia in the infant primate PL had relatively large somas, and a small arbor size. In contrast, microglia in the adolescent PL had a smaller soma, and a larger dendritic arbor. We then examined microglial morphology in the PL after a novel maternal separation protocol, to examine the effects of early life stress. After maternal separation, the microglia had increased soma size, arbor size and complexity. Surprisingly, strong effects were seen not only in the infant PL, but also in the adolescent PL from subjects who had experienced the separation many years earlier. We conclude that under normal maternal-rearing conditions, PL microglia morphology tracks PL neuronal growth, progressing to a more 'mature' phenotype by adolescence. Maternal separation has long-lasting effects on microglia, altering their normal developmental trajectory, and resulting in a 'hyper-ramified' phenotype that persists for years. We speculate that these changes have consequences for neuronal development in young primates.Significance Statement The paralaminar (PL) nucleus of the amygdala is an important source of plasticity, due to its unique repository of immature glutamatergic neurons. In Rhesus macaques, similar to human, PL immature neurons mature between birth and adolescence. This maturation process is likely supported by synaptogenesis, which requires microglia. Between infancy and adolescence in macaques, PL microglia became denser, and shifted to a 'ramified' phenotype, consistent with increased synaptic pruning functions. Early life stress in the form of maternal separation, however, blunted this normal trajectory, leading to a persistent 'hyper-ramified' microglial phenotype. We speculate that microglia hyper-ramification aligns with 'para-inflammatory' concepts of stress and may alter PL neuronal maturation and synapse formation in young animals.

Fragile X autosomal homolog 1 (FXR1), a member of the fragile X messenger riboprotein 1 family, has been linked to psychiatric disorders including autism and schizophrenia. Parvalbumin (PV) interneurons play critical roles in cortical processing, and have been implicated in FXR1-linked mental illnesses. Targeted deletion of FXR1 from PV interneurons in mice has been shown to alter cortical excitability and elicit schizophrenia-like behavior. This indicates that FXR1 regulates behaviorally relevant electrophysiological functions in PV interneurons. We therefore expressed a genetically-encoded hybrid voltage sensor in PV interneurons, and used voltage imaging in slices of mouse somatosensory cortex to assess the impact of targeted FXR1 deletion. These experiments showed that PV interneurons lacking FXR1 had excitatory synaptic potentials with larger amplitudes and shorter latencies compared to wild type. Synaptic potential rise-times, decay-times, and half-widths were also impacted to degrees that varied between cortical layer and synaptic input. Thus, FXR1 modulates the responsiveness of PV interneurons to excitatory synaptic inputs. This will enable FXR1 to control cortical processing in subtle ways, with the potential to influence behavior and contribute to psychiatric dysfunction.Significance statement Parvalbumin interneurons have been implicated in schizophrenia and autism. The RNA binding protein FXR1, a member of the fragile X protein family has been linked to mental illnesses and disabilities. Voltage imaging from parvalbumin interneurons in cortical slices revealed that targeted ablation of FXR1 from these neurons alters the amplitude and dynamics of their excitatory synaptic responses. These changes have the potential to alter circuit processing and behavior, and may be relevant to FXR1-linked mental illnesses.