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Cytokine expression patterns predict suppression of vulnerable neural circuits in a mouse model of Alzheimer′s disease bioRxiv. Neurosci. Pub Date : 2024-03-18 Dennis C. Chan, ChaeMin Kim, Rachel Y. Kang, Madison K. Kuhn, Lynne M. Beidler, Nanyin Zhang, Elizabeth A. Proctor
Alzheimer′s disease is a neurodegenerative disorder characterized by progressive amyloid plaque accumulation, tau tangle formation, neuroimmune dysregulation, synapse an neuron loss, and changes in neural circuit activation that lead to cognitive decline and dementia. Early molecular and cellular disease-instigating events occur 20 or more years prior to presentation of symptoms, making them difficult
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Validation of Enhancer Regions in Primary Human Neural Progenitor Cells using Capture STARR-seq bioRxiv. Neurosci. Pub Date : 2024-03-18 Sophia C. Gaynor-Gillett, Lijun Cheng, Manman Shi, Jason Liu, Gaoyuan Wang, Megan Spector, Mary Flaherty, Martha Wall, Ahyeon Hwang, Mengting Gu, Zhanlin Chen, Yuhang Chen, PsychENCODE Consortium, Jennifer R. Moran, Jing Zhang, Donghoon Lee, Mark Gerstein, Daniel Geschwind, Kevin P. White
Genome-wide association studies (GWAS) and expression analyses implicate noncoding regulatory regions as harboring risk factors for psychiatric disease, but functional characterization of these regions remains limited. We performed capture STARR-sequencing of over 78,000 candidate regions to identify active enhancers in primary human neural progenitor cells (phNPCs). We selected candidate regions by
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Neural dynamics of semantic control underlying generative storytelling bioRxiv. Neurosci. Pub Date : 2024-03-18 Clara Rastelli, Antonino Greco, Chiara Finocchiaro, Gabriele Penazzi, Christoph Braun, Nicola De Pisapia
Storytelling has been pivotal for the transmission of knowledge and cultural norms across human history. A crucial process underlying the generation of narratives is the exertion of cognitive control on the semantic representations stored in memory, a phenomenon referred as semantic control. Despite the extensive literature investigating the neural mechanisms of semantic control in generative language
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Translation of monosynaptic circuits underlying amygdala fMRI neurofeedback training bioRxiv. Neurosci. Pub Date : 2024-03-18 Lucas R. Trambaiolli, Chiara Maffei, Evan Dann, Claudinei Biazoli, Gleb Bezgin, Anastasia Yendiki, Suzanne Haber
Background: fMRI neurofeedback targeting the amygdala is a promising therapeutical tool in psychiatry. It induces resting-state functional connectivity (rsFC) changes between the amygdala and regions of the salience and default mode networks (SN and DMN, respectively). We hypothesize these rsFC changes happen on the amygdala's underlying anatomical circuits. Methods: We used the coordinates from regions
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Reduced avoidance bias to social threat signals in women taking oral contraceptives bioRxiv. Neurosci. Pub Date : 2024-03-18 Jasmin Thurley, Macia Buades Rotger, Georg Serfling, Thessa Howaldt, Nicole Reisch, Ulrike M. Kramer
Recent research has increasingly acknowledged the impact of oral contraceptives on affective behavior and stress responses; however, the underlying mechanisms are still not well understood. Studies have previously shown that steroid hormones modulate automatic approach and avoidance behavior. Here, we thus investigated the effects of oral contraceptives on approach and avoidance behavior and whether
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Single neurons and networks in the claustrum integrate input from widespread cortical sources bioRxiv. Neurosci. Pub Date : 2024-03-18 Andrew M Shelton, David K Oliver, Ivan P Lazarte, Joachim S Grimstvedt, Ishaan Kapoor, Jake A Swann, Caitlin A Ashcroft, Simon N Williams, Niall Conway, Selma Tir, Amy Robinson, Stuart N Peirson, Thomas Akam, Clifford Kentros, Menno P Witter, Simon JB Butt, Adam M Packer
The claustrum is thought to be one of the most highly interconnected forebrain structures but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons to understand how the structure's unique convergence of input and divergence of output support binding information streams.
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Large-scale color biases in the retinotopic functional architecture are region specific and shared across human brains bioRxiv. Neurosci. Pub Date : 2024-03-18 Michael M. Bannert, Andreas Bartels
Despite the functional specialization in visual cortex, there is growing evidence that the processing of chromatic and spatial visual features is intertwined. While past studies focused on visual field biases in retina and behaviour, large-scale dependencies between coding of color and retinotopic space are largely unexplored in the cortex. Here we asked whether spatial color biases are shared across
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Two long-axis dimensions of hippocampal cortical integration support memory function across the adult lifespan bioRxiv. Neurosci. Pub Date : 2024-03-18 Kristin Nordin, Robin Pedersen, Farshad Falahati, Jarkko Johansson, Filip Grill, Micael Andersson, Saana M Korkki, Lars Backman, Andrew Zalesky, Anna Rieckmann, Lars Nyberg, Alireza Salami
The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains
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The Diversified Astrocyte Developmental Programs are Modulated by Primary Ciliary Signaling bioRxiv. Neurosci. Pub Date : 2024-03-17 Lizheng Wang, Qianqian Guo, Sandesh Acharya, Xiao Zheng, Vanessa Huynh, Brandon Whitmore, Askar Yimit, Mehr Malhotra, Siddharth Chatterji, Nicole Rosin, Elodie Labit, Colten Chipak, Kelsea Gorzo, Jordan Haidey, David Elliott, Tina Ram, Qingrun Zhang, Hedwich Kuipers, Grant Gordon, Jeff Biernaskie, Jiami Guo
Astrocyte diversity is greatly influenced by local environmental modulation. Here, we report that the vast majority of brain astrocytes across the entire brain possess a singular primary cilium, a specialized signaling antenna localized to cell soma. Comparative single-cell transcriptomics reveals that primary cilia mediate canonical Shh signaling to modulate astrocyte subtype-specific core features
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Representing the dynamics of natural marmoset vocal behaviors in frontal cortex bioRxiv. Neurosci. Pub Date : 2024-03-17 Jingwen Li, Mikio Christian Aoi, Cory Miller
Here we tested the respective contributions of primate premotor and prefrontal cortex to support vocal behavior. We applied a model-based GLM analysis that better accounts for the inherent variance in natural, continuous behaviors to characterize the activity of neurons throughout frontal cortex as freely-moving marmosets engaged in conversational exchanges. While analyses revealed functional clusters
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Dissecting the binding mechanisms of synaptic membrane adhesion complexes using a micropattern based cellular model bioRxiv. Neurosci. Pub Date : 2024-03-17 Nathalie Piette, Pierre-Olivier Strale, Matthieu Lagardere, Camille Saphy, Carsten Reissner, Matthieu Munier, Markus Missler, Ingrid Chamma, Matthieu Sainlos, olivier Thoumine, Vincent Studer
The formation of adhesive cell-cell contacts is based on the intrinsic binding properties between specific transmembrane ligand-receptor pairs. In neurons, synaptic adhesion molecules provide a physical linkage between pre- and post-synaptic compartments, but the dynamics of these complexes in their actual membrane environments remain essentially unknown. To access such information, we developed a
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ATF4 orchestrates IL-1α-induced senescence in adult neural stem cells bioRxiv. Neurosci. Pub Date : 2024-03-17 Susanne Neumann, Eric P Thelin, Sreenivasa Raghavan Sankavaram, Sanna Persson, Leonor Fonseca, Noah Moruzzi, Ellen Iacobaeus, Maria Bergsland, Elena Popova, Michael Bader, Mikael Svensson, Alexander Espinosa, Ruxandra Covacu, Lou Brundin
Adult neural stem cells (NSC) are a potential source for the regeneration of damaged tissue during neuropathological conditions, but much remains unexplored. In an attempt to study the influence of neuroinflammation on NSCs, we generated a transgenic reporter rat strain that expresses the Discosoma sp. red (DsRed) fluorophore in NSCs and subjected it to traumatic brain injury (TBI). Transcriptomic
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Causal evidence for increased theta and gamma phase consistency in a parieto-frontal network during the maintenance of visual attention bioRxiv. Neurosci. Pub Date : 2024-03-17 Claire Bradley, Emily McCann, Abbey S Nydam, Paul E Dux, Jason B Mattingley
Endogenous visuo-spatial attention is under the control of a fronto-parietal network of brain regions. One key node in this network, the intra-parietal sulcus (IPS), plays a crucial role in maintaining endogenous attention, but little is known about its ongoing physiology and network dynamics during different attentional states. Here, we investigated the reactivity of the left IPS in response to brain
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Neurosphere culture derived from aged hippocampal dentate gyrus bioRxiv. Neurosci. Pub Date : 2024-03-17 Olga Vafaeva, Poommaree Namchaiw, Karl D. Murray, Elva Diaz, Hwai-Jong Cheng
The neurosphere assay is the gold standard for determining proliferative and differentiation potential of neural progenitor cells (NPCs) in neurogenesis studies. While several in vitro assays have been developed to model the process of neurogenesis, they have predominantly used embryonic and early postnatal NPCs derived from the dentate gyrus (DG). A limitation of these approaches is that they do not
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Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory bioRxiv. Neurosci. Pub Date : 2024-03-17 Naoki Yamawaki, Hande Login, Solbjørg Østergaard Feld-Jakobsen, Bernadett Mercedesz Molnar, Mads Zippor Kirkegaard, Maria Moltesen, Aleksandra Okrasa, Jelena Radulovic, Asami Tanimura
The claustrum complex is viewed as fundamental for higher order cognition; however, the circuit organization and function of its ventral subregion, the endopiriform (EN), are not well understood. Using circuit analyses in mice, we show that EN neurons defined by their projection to ventral CA1 (ENvCA1-proj. neurons) were a major source of afferents to ventral CA1 (vCA1), with diverging collaterals
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Whole-body connectome of a segmented annelid larva bioRxiv. Neurosci. Pub Date : 2024-03-17 Gaspar Jekely, Sanja Jasek, Martin Guhmann, Luis Alberto Bezares-Calderon, Elizabeth Williams, Reza Shahidi
Nervous systems coordinate effectors across the body during movements. We know little about the cellular-level structure of synaptic circuits for such body-wide control. Here we describe the whole-body synaptic connectome of a segmented larva of the marine annelid Platynereis dumerilii. We reconstructed and annotated over 9,000 neuronal and non-neuronal cells in a whole-body serial electron microscopy
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Dynamic role of GlyT1 as glycine sink or source: pharmacological implications for the gain control of NMDA receptors bioRxiv. Neurosci. Pub Date : 2024-03-17 Stéphane SUPPLISSON
Glycine transporter 1 (GlyT1) mediates termination of inhibitory glycinergic receptors signaling in the spinal cord and brainstem, and is also diffusely present in the forebrain. Here, it regulates the ambient glycine concentration influencing the "glycine"-site occupancy of N-methyl-D-aspartate (NMDARs). GlyT1 is a reversible transporter with a substantial, but not excessive, sodium-motive force for
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Naturalistic Object Representations Depend on Distance and Size Cues bioRxiv. Neurosci. Pub Date : 2024-03-17 Grant T. Fairchild, Desiree E. Holler, Sara Fabbri, Michael A. Gomez, Jacqueline C. Walsh-Snow
Egocentric distance and real-world size are important cues for object perception and action. Nevertheless, most studies of human vision rely on two-dimensional pictorial stimuli that convey ambiguous distance and size information. Here, we use fMRI to test whether pictures are represented differently in the human brain from real, tangible objects that convey unambiguous distance and size cues. Participants
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Neurodevelopmental Subtypes of Functional Brain Organization in the ABCD Study Using a Rigorous Analytic Framework bioRxiv. Neurosci. Pub Date : 2024-03-17 Jacob DeRosa, Naomi P. Friedman, Vince Calhoun, Marie T Banich
The current study demonstrates that an individual's resting-state functional connectivity (RSFC) is a dependable biomarker for identifying differential patterns of cognitive and emotional functioning during late childhood. Using baseline RSFC data from the Adolescent Brain Cognitive Development (ABCD) study, which includes children aged 9-11, we identified four distinct RSFC subtypes We introduce an
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An arrayed CRISPR/Cas9 screen identifies mTORC1 as a regulator of lipid droplet accumulation in APOE E3 and APOE KO iPSC-derived microglia bioRxiv. Neurosci. Pub Date : 2024-03-17 Sonja Meier, Anne Sofie Gry Larsen, Florian Wanke, Nicolas Mercado, Arianna Mei, Livia Takacs, Eva Suszanna Mracsko, Ludovic Collin, Martin Kampmann, Filip Roudnicky, Ravi Jagasia
Variants of the Apolipoprotein E (APOE) gene, particularly the E4 allele, are significantly associated with an increased risk of Alzheimer's Disease and have been implicated in neuroinflammatory processes due to disrupted lipid metabolism. Lipid alterations can manifest in glial cells as an excessive buildup of lipids, potentially contributing to neuroinflammation. In this study, we observed a heightened
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Spectral waveform analysis dissociates human cortical alpha rhythms bioRxiv. Neurosci. Pub Date : 2024-03-17 Janet Giehl, Markus Siegel
The non-sinusoidal waveform of neuronal oscillations reflects the physiological properties of underlying circuit interactions and may serve as an informative biomarker of healthy and diseased human brain function. However, little is known about which brain rhythms can be dissociated based on their waveform and methods to comprehensively characterize waveforms are missing. Here, we introduce a novel
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Internal monitoring of whisking and locomotion in the superior colliculus bioRxiv. Neurosci. Pub Date : 2024-03-17 Suma Chinta, Scott Pluta
To localize objects using active touch, our brain must merge its map of the body surface with an ongoing representation of self-motion. While such computations are often ascribed to the cerebral cortex, we examined the midbrain superior colliculus (SC), due to its close relationship with the sensory periphery as well as higher, motor-related brain regions. We discovered that active whisking kinematics
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Cholinergic Transmission in an Inducible Transgenic Mouse Model of Paroxysmal Dystonia bioRxiv. Neurosci. Pub Date : 2024-03-17 Mariangela Scarduzio, Karen Jaunarajs, David G Standaert
Altered interaction between striatonigral dopaminergic (DA) inputs and local acetylcholine (ACh) in striatum has long been hypothesized to play a central role in dystonia pathophysiology. Indeed, previous research across various genetic mouse models of human isolated dystonia has identified as a shared endophenotype with paradoxical excitation of striatal cholinergic interneurons (ChIs) activity in
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Synchrony between midbrain gene transcription and dopamine terminal regulation is modulated by chronic alcohol drinking bioRxiv. Neurosci. Pub Date : 2024-03-17 Zahra Z Farahbakhsh, Katherine M Holleran, Jonathon P Sens, Steve C Fordahl, Madelyn I Mauterer, Alberto J López, Verginia C Cuzon Carlson, Drew D Kiraly, Kathleen A Grant, Sara R Jones, Cody A Siciliano
Alcohol use disorder is marked by disrupted behavioral and emotional states which persist into abstinence. The enduring synaptic alterations that remain despite the absence of alcohol are of interest for interventions to prevent relapse. Here, 28 male rhesus macaques underwent over 20 months of alcohol drinking interspersed with three 30-day forced abstinence periods. After the last abstinence period
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FABEL: Forecasting Animal Behavioral Events with Deep Learning-Based Computer Vision bioRxiv. Neurosci. Pub Date : 2024-03-17 Adam Catto, Richard O'Connor, Kevin M. Braunscheidel, Paul J. Kenny, Li Shen
Behavioral neuroscience aims to provide a connection between neural phenomena and emergent organism-level behaviors. This requires perturbing the nervous system and observing behavioral outcomes, and comparing observed post-perturbation behavior with predicted counterfactual behavior and therefore accurate behavioral forecasts. In this study we present FABEL, a deep learning method for forecasting
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Putaminal dopamine modulates movement motivation in Parkinson's disease bioRxiv. Neurosci. Pub Date : 2024-03-17 Magdalena Banwinkler, Verena Dzialas, Lionel Rigoux, Adrian Asendorf, Hendrik Theis, Kathrin Giehl, Marc Tittgemeyer, Merle Hoenig, Thilo van Eimeren
The relative inability to produce effortful movements (akinesia) is the most specific motor sign of Parkinson's disease. The motor motivation hypothesis suggests that akinesia may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor
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Atypical retinal function in a mouse model of Fragile X syndrome bioRxiv. Neurosci. Pub Date : 2024-03-17 Anna L Vlasits, Maria Syeda, Annelise Wickman, Pedro Guzman, Tiffany M Schmidt
Altered function of peripheral sensory neurons is an emerging mechanism for symptoms of autism spectrum disorders. Visual sensitivities are common in autism, but whether differences in the retina might underlie these sensitivities is not well-understood. We explored retinal function in the Fmr1 knockout model of Fragile X syndrome, focusing on a specific type of retinal neuron, the "sustained On alpha"
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Social state gates vision using three circuit mechanisms in Drosophila bioRxiv. Neurosci. Pub Date : 2024-03-17 Catherine E. Schretter, Tom Hindmarsh Sten, Nathan Klapoetke, Mei Shao, Aljoscha Nern, Marisa Dreher, Daniel Bushey, Alice A. Robie, Adam L. Taylor, Kristin M. Branson, Adriane Otopalik, Vanessa Ruta, Gerald M. Rubin
Animals are often bombarded with visual information and must prioritize specific visual features based on their current needs. The neuronal circuits that detect and relay visual features have been well-studied. Yet, much less is known about how an animal adjusts its visual attention as its goals or environmental conditions change. During social behaviors, flies need to focus on nearby flies. Here,
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Transcriptional modulation unique to vulnerable motor neurons predict ALS across species and SOD gene mutations bioRxiv. Neurosci. Pub Date : 2024-03-17 Irene Mei, Susanne Nichterwitz, Melanie Leboeuf, Jik Nijssen, Isadora Lenoel, Dirk Repsilber, Christian S Lobsiger, Eva Hedlund
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons (MNs), which innervate skeletal muscles. However, certain MN groups including ocular MNs that regulate eye movement are relatively resilient to ALS. To reveal mechanisms of differential MN vulnerability, we investigate the transcriptional dynamics of two vulnerable and two resilient MN populations
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Widespread innervation of motoneurons by spinal V3 neurons globally amplifies locomotor output in mice. bioRxiv. Neurosci. Pub Date : 2024-03-17 Han Zhang, Dylan Deska-Gauthier, Colin S Mackay, Krishnapriya Hari, Ana M Lucas-Osma, Joanna Borowska-Fielding, Reese L Letawsky, Turgay Akay, Keith K Fenrich, David J Bennett, Ying Zhang
While considerable progress has been made in understanding the neuronal circuits that underlie the patterning of locomotor behaviours such as walking, less is known about the circuits that amplify motoneuron output to enable adaptable increases in muscle force across different locomotor intensities. Here, we demonstrate that an excitatory propriospinal neuron population (V3 neurons, Sim1+) forms a
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Spatial contextual information modulates affordance processing and early electrophysiological markers of scene perception bioRxiv. Neurosci. Pub Date : 2024-03-17 Clement Naveilhan, Maud Saulay-Carret, Raphael Zory, Stephen Ramanoel
Scene perception allows humans to extract information from their environment and plan navigation efficiently. The automatic extraction of potential paths in a scene, also referred to as navigational affordances is supported by scene-selective regions (SSRs) that enable efficient human navigation. Recent evidence suggests that the activity of these SSRs can be influenced by information from adjacent
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Lesion-remote astrocytes govern microglia-mediated white matter repair bioRxiv. Neurosci. Pub Date : 2024-03-17 Sarah McCallum, keshav B Suresh, Timothy Islam, Ann W Saustad, Oksana Shelest, Aditya Patil, David Dong Lee, Brandon Kwon, Inga Yenokian, Riki Kawaguchi, Connor Hammond Beveridge, Palak Manchanda, Caitlin E Randolph, Gordon P. Meares, Jasmine T Plummer, Ranjan Dutta, Simon RV Knott, Gaurav Chopra, Joshua E Burda
Spared regions of the damaged central nervous system undergo dynamic remodeling and exhibit a remarkable potential for therapeutic exploitation. Here, lesion-remote astrocytes (LRAs), which interact with viable neurons, glia and neural circuitry, undergo reactive transformations whose molecular and functional properties are poorly understood. Using multiple transcriptional profiling methods, we interrogated
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Efficiency and reliability in biological neural network architectures bioRxiv. Neurosci. Pub Date : 2024-03-17 Daniela Egas Santander, Christoph Pokorny, András Ecker, Jānis Lazovskis, Matteo Santoro, Jason P. Smith, Kathryn Hess, Ran Levi, Michael W. Reimann
Neurons in a neural circuit have been demonstrated to have astonishing diversity in terms of numbers and targets of their synaptic connectivity and the statistics of their spiking activity. We hypothesize that this is the result of an underlying struggle between reliability, robustness and efficiency of the information represented by their spike trains. Specifically, certain architectures of connectivity
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Low-grade systemic inflammation stimulates microglial turnover and accelerates the onset of Alzheimer's-like pathology bioRxiv. Neurosci. Pub Date : 2024-03-17 Monica Guerrer-Carrasco, Imogen Targett, Adrian Olmos-Alonso, Mariana Vargas-Caballero, Diego Gomez-Nicola
Several in vivo studies have shown that systemic inflammation, mimicked by LPS, triggers an inflammatory response in the CNS, driven by microglia, characterised by an increase in inflammatory cytokines and associated sickness behaviour. However, most studies induce relatively high systemic inflammation, not directly compared with the more common low grade inflammatory events experienced in humans during
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Rat primary cortical cell tri-culture to study effects of amyloid-beta on microglia function bioRxiv. Neurosci. Pub Date : 2024-03-17 Hyehyun Kim, Bryan Le, Noah Goshi, Kan Zhu, Ana Cristina Grodzki, Pamela J Lein, Min Zhao, Erkin Seker
INTRODUCTION: The etiology and progression of sporadic Alzheimer's Disease (AD) have been studied for decades. One proposed mechanism is that amyloid-beta (Aβ) proteins induce neuroinflammation, synapse loss, and neuronal cell death. Microglia play an especially important role in Aβ clearance, and alterations in microglial function due to aging or disease may result in Aβ accumulation and deleterious
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Human cortical neurons rapidly generated by direct ES cell programming integrate into stroke-injured rat cortex bioRxiv. Neurosci. Pub Date : 2024-03-17 Raquel Martinez-Curiel, Mazin Hajy, Oleg Tsupykov, Linda Jansson, Natalia Avaliani, Berta Coll-San Martin, Emanuela Monni, Galyna Skibo, Olle Lindvall, Sara Palma Tortosa, Zaal Kokaia
Stroke is a major cause of long-term disability in adult humans, the neuronal loss leading to motor, sensory, and cognitive impairments. Replacement of dead neurons by intracerebral transplantation of stem cell-derived neurons for reconstruction of injured neuronal networks has potential to become a novel therapeutic strategy to promote functional recovery after stroke. Here we describe a rapid and
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Cycle-frequency content EEG analysis improves the assessment of respiratory-related cortical activity bioRxiv. Neurosci. Pub Date : 2024-03-17 Xavier Navarro-Sune, Mathieu Raux, Anna L Hudson, Thomas Similowski, Mario Chavez
Time-Frequency (T-F) analysis of EEG is a common technique to characterise spectral changes in neural activity. This study explores the limitations of utilizing conventional spectral techniques in examining cyclic event-related cortical activities due to challenges, including high inter-trial variability. Introducing the Cycle-Frequency (C-F) analysis, we aim to enhance the evaluation of cycle-locked
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A feedback-driven IoT microfluidic, electrophysiology, and imaging platform for brain organoid studies bioRxiv. Neurosci. Pub Date : 2024-03-17 Kateryna Voitiuk, Spencer T. Seiler, Mirella Pessoa de Melo, Jinghui Geng, Sebastian Hernandez, Hunter E. Schweiger, Jess L. Sevetson, David F. Parks, Ash Robbins, Sebastia Torres-Montoya, Drew Ehrlich, Matthew A.T. Elliott, Tal Sharf, David Haussler, Mohammed A. Mostajo-Radji, Sofie R. Salama, Mircea Teodorescu
The analysis of tissue cultures, particularly brain organoids, takes a high degree of coordination, measurement, and monitoring. We have developed an automated research platform enabling independent devices to achieve collaborative objectives for feedback-driven cell culture studies. Unified by an Internet of Things (IoT) architecture, our approach enables continuous, communicative interactions among
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Redox-dependent synaptic clustering of gephyrin bioRxiv. Neurosci. Pub Date : 2024-03-17 Maria-Theresa Gehling, Filip Liebsch, Lianne Jacobs, Jan Riemer, Guenter Schwarz
Reactive oxygen species (ROS) play a central role in enhancing inhibitory signal transmission, thus extending their role beyond oxidative stress in disease and aging. However, the underlying molecular mechanisms mediating these functions have remained elusive. At inhibitory synapses, the scaffolding protein gephyrin clusters glycine and GABA type A receptors. Since gephyrin harbors multiple surface-exposed
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Dorsomedial Striatal Glutamatergic Transmission Inhibits Binge Drinking in Selectively Bred Crossed High Alcohol Preferring Mice bioRxiv. Neurosci. Pub Date : 2024-03-17 Stephen L Boehm, Meredith Bauer, Megan M McVey, Yanping Zhang
Crossed high alcohol preferring (cHAP) mice have been selectively bred to consume considerable amounts of alcohol resulting in binge drinking. The dorsal striatum (DS) is a brain region involved in action selection where the dorsomedial striatum (DMS) is involved in goal-directed action selection and dorsolateral striatum (DLS) is involved in habitual action selection. Alcohol use disorder (AUD) may
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Neuronal activity promotes axonal node-like clustering prior to myelination and remyelination in the central nervous system. bioRxiv. Neurosci. Pub Date : 2024-03-17 Rémi Ronzano, Clément Perrot, Elisa Mazuir, Melina Thetiot, Marie-Stéphane Aigrot, Paul Stheneur, François-Xavier Lejeune, Bruno Stankoff, Catherine Lubetzki, Nathalie Sol-Foulon, Anne Desmazieres
Nodes of Ranvier ensure the fast saltatory conduction along myelinated axons, through their enrichment in voltage-gated sodium and potassium channels. We and others have shown that node-like cluster assembly can occur before myelination. In multiple sclerosis, demyelination is associated with node of Ranvier disassembly, but node-like reassembly can occur prior to remyelination. Given the crucial role
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Cell-type specialization of layer 5 excitatory neurons in tactile behavior bioRxiv. Neurosci. Pub Date : 2024-03-17 Samson G King, Phillip Maire, Adam Mergenthal, Stefanie Walker, Samuel Andrew Hires
Layer 5 is the canonical output layer of sensory cortex. The two most numerous neural constituents of Layer 5 are pyramidal tract (PT) and intratelencephalic (IT) neurons. These output cell classes combine diverse sets of inputs and project to distinct locations across the brain, suggesting differing roles in sensory information processing. Here, we investigated the representation of touch and whisker
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Neurexins control the strength and precise timing of glycinergic inhibition in the auditory brainstem bioRxiv. Neurosci. Pub Date : 2024-03-16 He-Hai Jiang, Ruoxuan Xu, Xiupeng Nie, Zhenghui Su, Xiaoshan Xu, Ruiqi Pang, Yi Zhou, Fujun Luo
Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between
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Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain bioRxiv. Neurosci. Pub Date : 2024-03-16 Ya-Hui Lin, Li-Wen Wang, Yen-Hui Chen, Yi-Chieh Chan, Shang-Hsiu Hu, Sheng-Yan Wu, Chi-Shiun Chiang, Guan-Jie Huang, Shang-Da Yang, Shi-Wei Chu, Kuo-Chuan Wang, Chin-Hsien Lin, Pei-Hsin Huang, Hwai-Jong Cheng, Bi-Chang Chen, Li-An Chu
Tissue clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling
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Nuclear translocation of LINE-1 ORF1p alters nuclear envelope integrity and disrupts nucleocytoplasmic transport in human neurons bioRxiv. Neurosci. Pub Date : 2024-03-16 Rania Znaidi, Olivia Massiani-Beaudoin, Philippe Mailly, Heloise Monnet, The Brainbank Neuro- CEB Neuropathology Network, Rajiv L. Joshi, Julia Fuchs
LINE-1 retrotransposons are emerging as possible culprits in neurodegenerative diseases. However, the molecular mechanisms underlying the pathogenic role of LINE-1 and their encoded proteins ORF1p and ORF2p are still not completely understood. While the endonuclease and reverse transcriptase activities of ORF2p have been associated with DNA damage and inflammation, no pathogenic role has yet been assigned
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Corticostriatal responses to social reward are linked to trait reward sensitivity and subclinical substance use in young adults bioRxiv. Neurosci. Pub Date : 2024-03-16 James B Wyngaarden, Camille R Johnston, Daniel Sazhin, Jeffrey B Dennison, Ori Zaff, Dominic Fareri, Michael McCloskey, Lauren B Alloy, David V Smith, Johanna M Jarcho
Aberrant levels of reward sensitivity have been linked to substance use disorder and are characterized by alterations in reward processing in the ventral striatum (VS). Less is known about how reward sensitivity and subclinical substance use relate to striatal function during social rewards (e.g., positive peer feedback). Testing this relation is critical for predicting risk for development of substance
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Mitochondrial dysfunction drives a neuronal exhaustion phenotype in methylmalonic aciduria bioRxiv. Neurosci. Pub Date : 2024-03-16 Matthew Christopher Simon Denley, Monique S Straub, Giulio Marcionelli, Miriam A Güra, David Penton Ribas, Igor Delvendahl, Martin Poms, Beata Vekeriotaite, Federica Conte, Ferdinand von Meyenn, D Sean Froese, Matthias R Baumgartner
Methylmalonic aciduria (MMA) is an inborn error of metabolism resulting in loss of function of the enzyme methylmalonyl-CoA mutase (MMUT). Despite acute and persistent neurological symptoms, the pathogenesis of MMA in the central nervous system is poorly understood, which has contributed to a dearth of effective brain specific treatments. Here we utilised patient-derived induced pluripotent stem cells
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Contradictory behavioral effects of neuronal perturbations on behavioral responses to linearly polarized light in freely walking Drosophila bioRxiv. Neurosci. Pub Date : 2024-03-16 Anna V Titova, Andrew D Straw
Many insects can use the polarization of the skylight as a navigational cue. As shown previously, freely walking Drosophila orient along the e-vector of linearly polarized UV light presented both dorsally and ventrally. We are interested in the neuronal mechanisms leading to this behavior, and specifically how the central complex and its inputs are involved. We investigated the behavior of flies exposed
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M2M-InvNet: Human Motor Cortex Mapping from Multi-Muscle Response Using TMS and Generative 3D Convolutional Network bioRxiv. Neurosci. Pub Date : 2024-03-16 Md Navid Akbar, Mathew Yarossi, Sumientra Rampersad, Kyle Lockwood, Aria Masoomi, Eugene Tunik, Dana Brooks, Deniz Erdogmus
Transcranial magnetic stimulation (TMS) is often applied to the motor cortex to stimulate a collection of motor evoked potentials (MEPs) in groups of peripheral muscles. The causal interface between TMS and MEP is the selective activation of neurons in the motor cortex; moving around the TMS `spot' over the motor cortex causes different MEP responses. A question of interest is whether a collection
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The resolution of face perception varies systematically across the visual field bioRxiv. Neurosci. Pub Date : 2024-03-16 Annie Morsi, Valerie Goffaux, John A Greenwood
Visual abilities tend to vary predictably across the visual field - for simple low-level stimuli, visibility is better along the horizontal vs. vertical meridian and in the lower vs. upper visual field. In contrast, face perception abilities have been reported to show either distinct or entirely idiosyncratic patterns of variation in peripheral vision, suggesting a dissociation between the spatial
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Molecular dissection of HERV-W dependent microglial- and astroglial cell polarization bioRxiv. Neurosci. Pub Date : 2024-03-16 Joel Gruchot, Laura Reiche, Luisa Werner, Felisa Herrero, Jessica Schira-Heinen, Urs Meyer, Patrick Kuery
The endogenous retrovirus type W (HERV-W) is a human-specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found that the HERV-W envelope (ENV) protein negatively affects oligodendrogenesis and controls microglial cell polarization towards a myelinated axon associated and damaging phenotype. Such first functional assessments were conducted ex
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Correspondence of fentanyl brain pharmacokinetics and behavior measured via engineering opioids biosensors and computational ethology bioRxiv. Neurosci. Pub Date : 2024-03-16 Anand K Muthusamy, Matthew Rosenberg, Charlene H Kim, Alexander Z Wang, Haruka Ebisu, Theodore M Chin, Ashil Koranne, Jonathan S Marvin, Bruce N Cohen, Loren L Looger, Yuki Oka, Markus Meister, Henry A Lester
Despite the ongoing epidemic of opioid use disorder and death by fentanyl overdose, opioids remain the gold standard for analgesics. Pharmacokinetics (PK) dictates the individual's experience and utility of drugs; however, PK and behavioral outcomes have been conventionally studied in separate groups, even in preclinical models. To bridge this gap, we developed the first class of sensitive, selective
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Dynamin-2 Mutations Linked to Neonatal-onset Centronuclear Myopathy impair exocytosis and endocytosis in adrenal chromaffin cells. bioRxiv. Neurosci. Pub Date : 2024-03-16 Lucas Bayones, Maria Jose Guerra-Fernandez, Cindel Figuroa-Cares, Luciana Ines Gallo, Samuel Alfonso-Bueno, Ximena Baez-Matus, Arlek Gonzalez-Jamett, Ana Maria Cardenas, Fernando Diego Marengo
Dynamins are large GTPases whose primary function is to catalyze membrane scission during endocytosis, but also modulate other cellular processes, such as actin polymerization and vesicle trafficking. Recently, we reported that centronuclear myopathy associated dynamin-2 mutations, p.A618T and p.S619L, impair Ca2+-induced exocytosis of GLUT4 containing vesicles in immortalized human myoblasts. As exocytosis
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Even Small Visual Latencies Can Profoundly Impair Implicit Sensorimotor Learning bioRxiv. Neurosci. Pub Date : 2024-03-16 Alkis M. Hadjiosif, George Abraham, Tanvi Ranjan, Maurice A. Smith
Short sub-100ms visual feedback latencies are common in many types of human-computer interactions yet are known to markedly reduce performance in a wide variety of motor tasks from simple pointing to operating surgical robotics. These latencies are also present in the computer-based experiments used to study the sensorimotor learning that underlies the acquisition of motor performance. Inspired by
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The role of desmoplakin for neuronal function in the dentate gyrus and anxiety-related behavior bioRxiv. Neurosci. Pub Date : 2024-03-16 Keisuke Otsubo, Naoko Sakashita, Yuki Nishimoto, Yo Sato, Katsunori Kobayashi, Kanzo Suzuki, Eri Segi-Nishida
Desmoplakin (Dsp) is a component of desmosomal cell-cell junctions. In the central nervous system, Dsp is specifically expressed in the hippocampal dentate gyrus (DG). However, it is unclear how Dsp impacts hippocampal function and its related behaviors. In this study, we provide evidence that Dsp in the DG maintains hippocampal functions, including neuronal activity and adult neurogenesis, and contributes
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Neural correlates in the time course of inferences: costs and benefits for less-skilled readers at university level. bioRxiv. Neurosci. Pub Date : 2024-03-16 Mabel Urrutia, Esteban Pino, Maria Troncoso-Seguel, Claudio Bustos, Pamela Guevara, Karina Torres-Ocampo, Sandra Mariangel, Yang Fu, Hipolito Marrero
Inferences are an indicator of a greater reading comprehension, as they imply a combination of implicit and explicit information that usually combines a textual representation with background knowledge of the reader. The aim of this study is to explore the costs and benefits of the time course of inferences in university students with reading comprehension difficulties at 3 stages during a narration
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Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system. bioRxiv. Neurosci. Pub Date : 2024-03-16 Harold Haun, Raul Hernandez, Luzi Yan, Meghan Flanigan, Olivia Hon, Sophia Lee, Hernan Mendez, Alison Roland, Lisa Taxier, Thomas Louis kash
High intensity alcohol drinking during binge episodes overwhelmingly contributes to the socioeconomic burden created by Alcohol Use Disorders (AUD). Novel interventions are needed to add to the current therapeutic toolkit and nociceptin receptor (NOP) antagonists have shown promise in reducing heavy drinking days in patients with an AUD. However, an endogenous locus of nociceptin peptide and discrete
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Task-related modulation of event-related potentials does not reflect changes to sensory representations bioRxiv. Neurosci. Pub Date : 2024-03-16 Reuben Rideaux
Attention supports efficient perception by increasing the neural signals of targets while supressing those of distractors. Decades of work studying the event-related potentials of electroencephalography (EEG) recordings have established our understanding of attention in the human brain, but many aspects of this phenomenon remain unknown. Several recent studies suggest that multivariate analyses may
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High-throughput analysis of dendritic and axonal arbors reveals transcriptomic correlates of neuroanatomy bioRxiv. Neurosci. Pub Date : 2024-03-16 Olga Gliko, Matt Mallory, Rachel Dalley, Rohan Gala, James Gornet, Hongkui Zeng, Staci Sorensen, Uygar Sumbul
Neuronal anatomy is central to the organization and function of brain cell types. However, anatomical variability within apparently homogeneous populations of cells can obscure such insights. Here, we report large-scale automation of neuronal morphology reconstruction and analysis on a dataset of 813 inhibitory neurons characterized using the Patch-seq method, which enables measurement of multiple
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Non-Negative Matrix Factorization for Analyzing State Dependent Neuronal Network Dynamics in Calcium Recordings bioRxiv. Neurosci. Pub Date : 2024-03-16 Daniel Carbonero, Jad Noueihed, Mark A Kramer, John A White
Calcium imaging allows recording from hundreds of neurons in vivo with the ability to resolve single cell activity. Evaluating and analyzing neuronal responses, while also considering all dimensions of the data set to make specific conclusions, is extremely difficult. Often, descriptive statistics are used to analyze these forms of data. These analyses, however, remove variance by averaging the responses