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Mashup Score: 0Cell type- and layer-specific plasticity of olfactory bulb interneurons following olfactory sensory neuron ablation - 17 hour(s) ago
Lifelong neurogenesis endows the mouse olfactory system with a capacity for regeneration that is unique in the mammalian nervous system. Throughout life, olfactory sensory neurons (OSNs) are generated from olfactory epithelium (OE) stem cells in the nose, while the subventricular zone generates neuroblasts that migrate to the olfactory bulb (OB) and differentiate into multiple populations of inhibitory interneurons. Methimazole (MMZ) selectively ablates OSNs, but OE neurogenesis enables OSN repopulation and gradual recovery of OSN input to the OB within six weeks. However, it is not known how OB interneurons are affected by this loss and subsequent regeneration of OSN input following MMZ treatment. We found that dopaminergic neuron density was significantly reduced 7-14 days post-MMZ but recovered substantially at 35 days. The density of parvalbumin-expressing interneurons was unaffected by MMZ; however, their soma size was significantly reduced at 7-14 days post-MMZ, recovering by 35
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 0Reward perseveration is shaped by GABAA-mediated dopamine pauses - 17 hour(s) ago
Extinction learning is an essential form of cognitive flexibility, which enables obsolete reward associations to be discarded. Its downregulation can lead to perseveration, a symptom seen in several neuropsychiatric disorders. This balance is regulated by dopamine from VTADA (ventral tegmental area dopamine) neurons, which in turn are largely controlled by GABA (gamma amino-butyric acid) synapses. However, the causal relationship of these circuit elements to extinction and perseveration remain incompletely understood. Here, we employ an innovative drug targeting technology, DART (drug acutely restricted by tethering), to selectively block GABAA receptors on VTADA neurons as mice engage in Pavlovian learning. DART eliminated GABAA mediated pauses; brief decrements in VTADA activity canonically thought to drive extinction learning. However, contrary to the hypothesis that blocking VTADA pauses should eliminate extinction learning, we observed the opposite: accelerated extinction learning
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Mashup Score: 1
Alzheimers disease leads to progressive neurodegeneration and dementia. Alzheimers disease primarily affects older adults with neuropathological changes including amyloid beta deposition, neuroinflammation, and neurodegeneration. We have previously demonstrated that systemic treatment with stem cell factor, SCF, and granulocyte colony stimulating factor, GCSF, reduces amyloid beta load, increases amyloid beta uptake by activated microglia and macrophages, reduces neuroinflammation, and restores dendrites and synapses in the brains of aged APP–PS1 mice. However, the mechanisms underlying SCF–GCSF–enhanced brain repair in aged APP–PS1 mice remain unclear. This study used a transcriptomic approach to explore the mechanisms by which SCF–GCSF treatment alters the functions of microglia and macrophages in the brains of 28–month–old APP–PS1 mice. After 5–day injections of SCF–GCSF, single–cell RNA sequencing was performed on CD11b positive microglia and macrophages isolated from the brain. Fl
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Mashup Score: 8Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils - 17 hour(s) ago
Microglia, the primary immune cells of the central nervous system, play a crucial role in maintaining brain homeostasis through phagocytosis of various substrates, including amyloid-β (Aβ) fibrils, a hallmark of Alzheimer disease (AD) pathology. However, the molecular mechanisms regulating microglial Aβ uptake remain poorly understood. Here, we identified GPR34, a Gi/o-coupled receptor highly expressed in microglia, as a novel regulator of fibrillar Aβ phagocytosis. Treatment with a selective GPR34 agonist, M1, specifically enhanced uptake of Aβ fibrils, but not its monomer or oligomer, in both mouse and human microglia. Mechanistically, M1 reduced intracellular cAMP levels, which inversely correlated with Aβ uptake activity. Importantly, a single intrahippocampal injection of M1 in an AD mouse model significantly increased microglial Aβ uptake in vivo. Furthermore, single-nucleus RNA-sequencing analysis of Japanese AD patient samples revealed a significant reduction of GPR34 expressio
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Mashup Score: 1Limited cognitive resources reduce the language predictability benefit across the adult lifespan - 17 hour(s) ago
In everyday communication, humans predict upcoming language seemingly effortlessly. However, it remains unclear to what extent the formation of such predictions taxes executive resources. Our study set out to investigate how a limitation of executive resources impacts natural language prediction on multiple timescales in a novel dual-task paradigm, and how this impact is modulated by age. Participants (N = 175; 18-85 years) read short newspaper articles, presented word by word in varying font colours. This self-paced reading task was either performed in isolation or paired with a competing n-back task (1-back or 2-back) on the words’ font colour. We measured word-level reading time and block-level reading comprehension as well as n-back performance. To quantify word predictability, we estimated word surprisal on four distinct timescales (i.e., context lengths ranging from words to paragraphs) using a large language model. Under high cognitive load, adults aged 60 and over benefited mos
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Mashup Score: 0A TRANSLAMINAR SPACETIME CODE SUPPORTS TOUCH-EVOKED TRAVELING WAVES - 17 hour(s) ago
Linking sensory-evoked traveling waves to underlying circuit patterns is critical to understanding the neural basis of sensory perception. To form this link, we performed simultaneous electrophysiology and two-photon calcium imaging through transparent NeuroGrids and mapped touch-evoked cortical traveling waves and their underlying microcircuit dynamics. In awake mice, both passive and active whisker touch elicited traveling waves within and across barrels, with a fast early component followed by a variable late wave that lasted hundreds of milliseconds post-stimulus. Strikingly, late-wave dynamics were modulated by stimulus value and correlated with task performance. Mechanistically, the late wave component was i) modulated by motor feedback, ii) complemented by a sparse ensemble pattern across layer 2/3, which a balanced-state network model reconciled via inhibitory stabilization, and iii) aligned to regenerative Layer-5 apical dendritic Ca2+ events. Our results reveal a translaminar
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Mashup Score: 0Fitness incentives to male fighters undermine fighting performance in intergroup contests - 17 hour(s) ago
In humans and other animal societies, groups engage in intergroup conflicts over resources. The success of groups in these conflicts depends on individual contributions to collective fighting, yet individuals may have personal fitness incentives to defect rather than fight, which could undermine group performance. Here we test the hypothesis that personal fitness incentives affect intergroup conflict success in wild banded mongooses (Mungos mungo). In this species, intergroup fights are sometimes initiated by estrous females, who gain outgroup matings while their male group-mates contribute most of the fighting effort. We found that group fighting success was highest when a group’s females were in estrus, suggesting that, although females may initiate fights, their male group-mates seem motivated to chase away rival groups to defend their paternity. Surprisingly, we found that groups that won fights conceded more paternity to their rivals than groups that lost. In other words, behavior
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Mashup Score: 0
Conflict is one of the most critical factors affecting the behavior of animals related to their reproduction and survival, with aggressive interactions being central to acquiring resources or mating partners. This phenomenon is more common among males than females, impacting reproduction strategy and beginning of biparental care. Investigating such interactions in species closely related to social species can be illuminating, offering valuable insights into the factors that influence the emergence and maintenance of more complex social behaviors. In this context, we present a field study of male-male agonistic behavior in the wood-feeding cockroach, Panesthia angustipennis. Panesthia is the closest genus to the subsocial genus Salganea, which is known for its biparental care. Our field observations reveal a characteristic behavior where one male pushes a rival away from a female. The victorious male repeatedly returns to a specific site near the female, suggesting a strategy to minimiz
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Mashup Score: 0
The estrous cycle regulates reproductive events and hormone changes in female mammals and is analogous to the menstrual cycle in humans. Monitoring this cycle is necessary as it serves as a biomarker for overall health and is crucial for interpreting study results. The estrous cycle comprises four stages influenced by fluctuating levels of hormones, mainly estradiol and progesterone. Tracking the cycle traditionally relies on vaginal cytology, which categorizes stages based on three epithelial cell concentrations. However, this method has limitations, including time-consuming training and variable accuracy among researchers. To address these challenges, this study assessed the feasibility and reliability of two machine learning methods. An object detection-based machine learning model, Object Detection Estrous Staging (ODES), was employed to identify cell types throughout the estrous cycle in mice. A dataset of 555 vaginal cytology images with four different stains was annotated, with
Source: www.biorxiv.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 2Intestinal epigenomic alterations are associated with a dysregulated nutrient absorption phenotype in obesity - 17 hour(s) ago
Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work found that dietary glucose hyperabsorption occurs in some obese subjects, but detailed transcriptional or epigenomic features of the intestine associated with this phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as lean, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subjects have significantly upregulated dietary nutrient absorption proteins and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting suggested that enhanced binding of HNF4G promotes the o
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Cell type- and layer-specific plasticity of olfactory bulb interneurons following olfactory sensory neuron ablation https://t.co/wp7dujGLce #bioRxiv