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Mashup Score: 0Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis - 1 hour(s) ago
During inner ear semicircular canal morphogenesis in zebrafish, patterned canal-genesis zones express genes for extracellular matrix component synthesis. These include hyaluronan and the hyaluronan-binding chondroitin sulfate proteoglycan Versican, which are abundant in the matrices of many developing organs. Charged hyaluronate polymers play a key role in canal morphogenesis through osmotic swelling. However, the developmental factor(s) that control the synthesis of the matrix components and regulation of hyaluronate density and swelling are unknown. Here, we identify the transcription factor, Lmx1b, as a positive transcriptional regulator of hyaluronan, Versican, and chondroitin synthesis genes crucial for canal morphogenesis. We show that Versican regulates hyaluronan density through its protein core, whereas the charged chondroitin side chains contribute to the osmotic swelling of hyaluronate. Versican-tuned properties of hyaluronate matrices may be a broadly used mechanism in morp
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Mashup Score: 0Survival, Movement, and Lifespan: Decoding the Roles of Patched-Related (Ptr) in Drosophila melanogaster - 1 hour(s) ago
Patched-related (Ptr) is a transmembrane protein implicated in developmental processes in Drosophila melanogaster , yet its precise role remains incompletely understood. Here, we use Ptr23c null mutants to investigate the functional significance of Ptr through the entire life cycle monitoring survival during embryonic, larval, pupal and adult development, and studying larval locomotion and muscle structure. We report that Ptr23c larvae displayed impaired hatching, indicative of defective embryonic development. Moreover, mutant larvae exhibited reduced mobility and lethargy, suggesting a potential involvement of Ptr in neuromuscular function. Morphological analysis of somatic muscles in mutant larvae revealed enlarged cell nuclei. Despite high pre-adult mortality, a subset of Ptr23c mutant adults display an unexpected extension in lifespan compared to controls, implicating Ptr in the regulation of longevity. Our findings provide critical insights into the multifaceted role of Ptr in Dro
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Mashup Score: 1Flp-recombinase mouse line for genetic manipulation of ipRGCs - 1 hour(s) ago
Light has myriad impacts on behavior, health, and physiology. These signals originate in the retina and are relayed to the brain by more than 40 types of retinal ganglion cells (RGCs). Despite a growing appreciation for the diversity of RGCs, how these diverse channels of light information are ultimately integrated by the ~50 retinorecipient brain targets to drive these light-evoked effects is a major open question. This gap in understanding primarily stems from a lack of genetic tools that specifically label, manipulate, or ablate specific RGC types. Here, we report the generation and characterization of a new mouse line (Opn4FlpO), in which FlpO is expressed from the Opn4 locus, to manipulate the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells. We find that the Opn4FlpO line, when crossed to multiple reporters, drives expression that is confined to ipRGCs and primarily labels the M1-M3 subtypes. Labeled cells in this mouse line show the expected intrinsic,
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Mashup Score: 0Sex differences emerge after the menopause transition: Females show accelerated decline in episodic memory for spatial context at midlife - 1 hour(s) ago
Background and Objectives: The ability to remember past events in rich contextual detail (episodic memory) declines with advancing age, with accelerated decline around midlife. Past research indicates there may be sex differences in cognitive aging trajectories and risk for age-related neurodegenerative diseases, i.e. Alzheimer’s Disease. Yet, little is known about how biological sex affects episodic memory in the adult lifespan. We examined age differences in episodic memory for spatial context in males and females. Research Design and Methods: 192 adults aged 21 to 65 (M=44, SD=13, 134 females) completed a face-location task measuring spatial context memory (correct spatial context retrieval rates) and facial item memory (correct recognition rates), and the California Verbal Learning Test version II (CVLT-II) measuring verbal item memory (long free recall, cued recall, and recognition rates). Changepoint regression analysis was used to estimate the slope of memory across age and any
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Mashup Score: 0Sex differences in change-of-mind neuroeconomic decision-making is modulated by LINC00473 in medial prefrontal cortex - 1 hour(s) ago
Changing ones mind is a complex cognitive phenomenon involving a continuous re-appraisal of the trade-off between past costs and future value. Recent work modeling this behavior across species has established associations between aspects of this choice process and their contributions to altered decision-making in psychopathology. Here, we investigated the actions in medial prefrontal cortex (mPFC) neurons of long intergenic non-coding RNA, LINC00473, known to induce stress resilience in a striking sex-dependent manner, but whose role in cognitive function is unknown. We characterized complex decision-making behavior in male and female mice longitudinally in our neuroeconomic foraging paradigm, Restaurant Row, following virus-mediated LINC00473 expression in mPFC neurons. On this task, mice foraged for their primary source of food among varying costs (delays) and subjective value (flavors) while on a limited time-budget during which decisions to accept and wait for rewards were separate
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Mashup Score: 0Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury - 1 hour(s) ago
Traumatic injury to the spinal cord (SCI) results in immediate necrosis and delayed secondary expansion of neurological damage, often resulting in lifelong paralysis, neurosensory dysfunction, and chronic pain. Progress hemorrhagic necrosis (PHN) and excessive excitation are the primary sources of neural injury triggered by various insults, causing neuronal cytotoxicity and the gradual enlargement of lesions. Recent approaches have involved blocking TRPM4, a contributor to PHN, using the sulfonylurea (SUR) subunits regulator glibenclamide. However, since SUR subunits are expressed in both neurons and glial cells in the spinal cord and sensory neurons, forming functional KATP channels, the use of glibenclamide can exacerbate the development of SCI-induced chronic pain. In this study, we explored a treatment strategy involving the administration of glibenclamide, which suppresses PHN, and diazoxide, which protects against neuronal excitation and inflammation, at different time intervals
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Mashup Score: 0A novel critic signal in identified midbrain dopaminergic neurons of mice training in operant tasks - 1 hour(s) ago
In the canonical interpretation of phasic activation of dopaminergic neurons during Pavlovian conditioning, initially cell firing is triggered by unexpected rewards. Upon learning, activation instead follows the reward-predictive conditioned stimulus. When expected rewards are withheld, firing is inhibited. Here, we recorded optogenetically identified dopaminergic neurons of ventral tegmental area (VTA) in mice training in successive operant sensory discrimination tasks. A delay was imposed between nose-poke choices and trial outcome signals (reward or punishment). While animals were still performing at sub-criterion levels in the task, firing increased after correct choices, but prior to trial outcome signals. Thus, the neurons predicted whether choices would be rewarded, despite the animals’ poor behavioral performance. Surprisingly, these neurons also fired after reward delivery, as if the rewards had been unexpected, but the cells were inhibited after punishment signals, as if the
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Mashup Score: 0Eye movements reveal age differences in how arousal modulates saliency priority but not attention processing speed - 1 hour(s) ago
The arousal-biased competition theory posits that inducing arousal increases attentional priority of salient stimuli while reducing priority of non-pertinent stimuli. However, unlike in young adults, older adults rarely exhibit shifts in priority under increased arousal, and prior studies have proposed different neural mechanisms to explain how arousal differentially modulates selective attention in older adults. Therefore, we investigated how the threat of unpredictable shock differentially modulates attentional control mechanisms in young and older adults by observing eye movements. Participants completed two oculomotor search tasks in which the salient distractor was typically captured by attention (singleton search) or proactively suppressed (feature search). We found that arousal did not modulate attentional priority for any stimulus among older adults nor affect the speed of attention processing in either age group. Furthermore, we observed that arousal modulated pupil sizes and
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Mashup Score: 1
Mature neurons maintain their distinctive morphology for extended periods in adult life. Compared to developmental neurite outgrowth, axon guidance, and target selection, relatively little is known of mechanisms that maintain mature neuron morphology. Loss of function in C. elegans DIP-2, a member of the conserved lipid metabolic regulator Dip2 family, results in progressive overgrowth of neurites in adults. We find that dip-2 mutants display specific genetic interactions with sax-2, the C. elegans ortholog of Drosophila Furry and mammalian FRY. Combined loss of DIP-2 and SAX-2 results in severe disruption of neuronal morphology maintenance accompanied by increased release of neuronal extracellular vesicles (EVs). By screening for suppressors of dip-2 sax-2 double mutant defects we identified gain-of-function (gf) mutations in the conserved Dopey family protein PAD-1 and its associated phospholipid flippase TAT-5/ATP9A. In dip-2 sax-2 double mutants carrying either pad-1(gf) or tat-5(g
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Mashup Score: 0Establishing neuroanatomical correspondences across mouse and marmoset brain structures - 1 hour(s) ago
Interest in the common marmoset is growing due to evolutionarily proximity to humans compared to laboratory mice, necessitating a comparison of mouse and marmoset brain architectures, including connectivity and cell type distributions. Creating an actionable comparative platform is challenging since these brains have distinct spatial organizations and expert neuroanatomists disagree. We propose a general theoretical framework to relate named atlas compartments across taxa and use it to establish a detailed correspondence between marmoset and mice brains. Contrary to conventional wisdom that brain structures may be easier to relate at higher levels of the atlas hierarchy, we find that finer parcellations at the leaf levels offer greater reconcilability despite naming discrepancies. Utilizing existing atlases and associated literature, we created a list of leaf- level structures for both species and establish five types of correspondence between them. One-to-one relations were found betw
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Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis https://t.co/CIPd0dZq0H #bioRxiv