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Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier Neuron (IF 14.7) Pub Date : 2024-08-26 Yuan Xie, Fan Yang, Liqun He, Hua Huang, Min Chao, Haiyan Cao, Yaqin Hu, Zhicheng Fan, Yaohong Zhai, Wenjian Zhao, Xian Liu, Ruozhu Zhao, Bing Xiao, Xinxin Shi, Yuancheng Luo, Jinlong Yin, Dayun Feng, Jean-Philippe Hugnot, Lars Muhl, Anna Dimberg, Christer Betsholtz, Yanyu Zhang, Liang Wang, Lei Zhang
The blood-brain barrier (BBB) serves as a crucial vascular specialization, shielding and nourishing brain neurons and glia while impeding drug delivery. Here, we conducted single-cell mRNA sequencing of human cerebrovascular cells from 13 surgically resected glioma samples and adjacent normal brain tissue. The transcriptomes of 103,230 cells were mapped, including 57,324 endothelial cells (ECs) and
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Microglia’s heroic battle against neurodegeneration Neuron (IF 14.7) Pub Date : 2024-08-21 Yogita M. Kattimani, Ari Waisman
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Mentoring to propagate racial inclusivity in neuroscience Neuron (IF 14.7) Pub Date : 2024-08-21 Jose Rodriguez-Romaguera, Gregory J. Quirk
Mentoring the next generation of neuroscientists from historically excluded backgrounds brings several challenges. Successful mentor-mentee relationships are critical for addressing these challenges. Rodriguez-Romaguera and Quirk reflect on lessons learned from their cross-racial mentor-mentee relationship that could apply to many mentors.
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The lateral septum returns to the center stage of brain reward Neuron (IF 14.7) Pub Date : 2024-08-21 Jonathan J. Chow, Rajtarun Madangopal, Yavin Shaham
In this issue of Neuron, Chen et al.1 found that lateral septum Esr1-expressing cells respond to both non-drug and drug rewards. Mice will lever press for optogenetic stimulation of these neurons, which are also critical to methamphetamine locomotor sensitization, conditioned place preference, self-administration, and reinstatement.
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Keeping track of time: An interaction of mossy fibers and climbing fibers Neuron (IF 14.7) Pub Date : 2024-08-21 Robin Broersen, Chris I. De Zeeuw
Precisely tracking time over second-long timescales is important for accurate anticipation and consequential actions, yet the neurobiological underpinnings remain unknown. In this issue of Neuron, Garcia-Garcia and colleagues1 show that computations in the cerebellum resulting from interactions between the mossy fiber and climbing fiber pathways contribute to long-interval learning during operant conditioning
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Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism Neuron (IF 14.7) Pub Date : 2024-08-13 Caterina P. Profaci, Sean S. Harvey, Kaja Bajc, Tony Z. Zhang, Danielle A. Jeffrey, Alexander Z. Zhang, Kelsey M. Nemec, Hayk Davtyan, Carleigh A. O’Brien, Gabriel L. McKinsey, Aaron Longworth, Timothy P. McMullen, Joia K. Capocchi, Jessica G. Gonzalez, Devon A. Lawson, Thomas D. Arnold, Dimitrios Davalos, Mathew Blurton-Jones, Fabrice Dabertrand, F. Chris Bennett, Richard Daneman
Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain’s most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial
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Internal world models in humans, animals, and AI Neuron (IF 14.7) Pub Date : 2024-08-09 Ilka Diester, Marlene Bartos, Joschka Bödecker, Adam Kortylewski, Christian Leibold, Johannes Letzkus, Matthew M. Nour, Monika Schönauer, Andrew Straw, Abhinav Valada, Andreas Vlachos, Thomas Brox
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A shared model-based linguistic space for transmitting our thoughts from brain to brain in natural conversations Neuron (IF 14.7) Pub Date : 2024-08-02 Zaid Zada, Ariel Goldstein, Sebastian Michelmann, Erez Simony, Amy Price, Liat Hasenfratz, Emily Barham, Asieh Zadbood, Werner Doyle, Daniel Friedman, Patricia Dugan, Lucia Melloni, Sasha Devore, Adeen Flinker, Orrin Devinsky, Samuel A. Nastase, Uri Hasson
Effective communication hinges on a mutual understanding of word meaning in different contexts. We recorded brain activity using electrocorticography during spontaneous, face-to-face conversations in five pairs of epilepsy patients. We developed a model-based coupling framework that aligns brain activity in both speaker and listener to a shared embedding space from a large language model (LLM). The
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Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions Neuron (IF 14.7) Pub Date : 2024-07-29 Isabel Lam, Alain Ndayisaba, Amanda J. Lewis, YuHong Fu, Giselle T. Sagredo, Anastasia Kuzkina, Ludovica Zaccagnini, Meral Celikag, Jackson Sandoe, Ricardo L. Sanz, Aazam Vahdatshoar, Timothy D. Martin, Nader Morshed, Toru Ichihashi, Arati Tripathi, Nagendran Ramalingam, Charlotte Oettgen-Suazo, Theresa Bartels, Manel Boussouf, Max Schäbinger, Erinc Hallacli, Xin Jiang, Amrita Verma, Challana Tea,
The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed screenable iPSC “inclusionopathy” models utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like
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Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology Neuron (IF 14.7) Pub Date : 2024-07-29 Keith R. Murphy, Jordan S. Farrell, Jonas Bendig, Anish Mitra, Charlotte Luff, Ina A. Stelzer, Hiroshi Yamaguchi, Christopher C. Angelakos, Mihyun Choi, Wenjie Bian, Tommaso DiIanni, Esther Martinez Pujol, Noa Matosevich, Raag Airan, Brice Gaudillière, Elisa E. Konofagou, Kim Butts-Pauly, Ivan Soltesz, Luis de Lecea
Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent
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Cell-class-specific electric field entrainment of neural activity Neuron (IF 14.7) Pub Date : 2024-07-26 Soo Yeun Lee, Konstantinos Kozalakis, Fahimeh Baftizadeh, Luke Campagnola, Tim Jarsky, Christof Koch, Costas A. Anastassiou
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Dissecting attention: Rate modulation vs. phase locking Neuron (IF 14.7) Pub Date : 2024-07-17 Moein Esghaei, Julio Martinez-Trujillo, Stefan Treue
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Thalamic cells and pathway for social memory processing and storage Neuron (IF 14.7) Pub Date : 2024-07-17 Wen-Jun Gao
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Internal world models in humans, animals, and AI Neuron (IF 14.7) Pub Date : 2024-07-17 Ilka Diester, Marlene Bartos, Joschka Bödecker, Adam Kortylewski, Christian Leibold, Johannes Letzkus, Matthew M. Nour, Monika Schönauer, Andrew Straw, Abhinav Valada, Andreas Vlachos, Thomas Brox
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Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells Neuron (IF 14.7) Pub Date : 2024-07-17 Feng Tian, Yuyan Cheng, Songlin Zhou, Qianbin Wang, Aboozar Monavarfeshani, Kun Gao, Weiqian Jiang, Riki Kawaguchi, Qing Wang, Mingjun Tang, Ryan Donahue, Huyan Meng, Yu Zhang, Anne Jacobi, Wenjun Yan, Jiani Yin, Xinyi Cai, Zhiyun Yang, Shane Hegarty, Joanna Stanicka, Phillip Dmitriev, Daniel Taub, Junjie Zhu, Clifford J. Woolf, Joshua R. Sanes, Daniel H. Geschwind, Zhigang He
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Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells Neuron (IF 14.7) Pub Date : 2024-07-17 Feng Tian, Yuyan Cheng, Songlin Zhou, Qianbin Wang, Aboozar Monavarfeshani, Kun Gao, Weiqian Jiang, Riki Kawaguchi, Qing Wang, Mingjun Tang, Ryan Donahue, Huyan Meng, Yu Zhang, Anne Jacobi, Wenjun Yan, Jiani Yin, Xinyi Cai, Zhiyun Yang, Shane Hegarty, Joanna Stanicka, Phillip Dmitriev, Daniel Taub, Junjie Zhu, Clifford J. Woolf, Joshua R. Sanes, Daniel H. Geschwind, Zhigang He
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Pupil constriction by contrast for contrast Neuron (IF 14.7) Pub Date : 2024-07-17 Michael Tri H. Do
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Sensory choices as logistic classification Neuron (IF 14.7) Pub Date : 2024-07-15 Matteo Carandini
Logistic classification is a simple way to make choices based on a set of factors: give each factor a weight, sum the results, and use the sum to set the log odds of a random draw. This operation is known to describe human and animal choices based on value (economic decisions). There is increasing evidence that it also describes choices based on sensory inputs (perceptual decisions), presented across
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Propofol anesthesia destabilizes neural dynamics across cortex Neuron (IF 14.7) Pub Date : 2024-07-15 Adam J. Eisen, Leo Kozachkov, André M. Bastos, Jacob A. Donoghue, Meredith K. Mahnke, Scott L. Brincat, Sarthak Chandra, John Tauber, Emery N. Brown, Ila R. Fiete, Earl K. Miller
Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability—the ability of the brain to balance excitability with the need to be stable and controllable. To test this hypothesis, we developed a method for quantifying changes in population-level dynamic stability in complex systems: delayed linear analysis for stability estimation
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Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs Neuron (IF 14.7) Pub Date : 2024-07-12 Yoshimitsu Nakanishi, Mayuko Izumi, Hiroaki Matsushita, Yoshihisa Koyama, Diego Diez, Hyota Takamatsu, Shohei Koyama, Masayuki Nishide, Maiko Naito, Yumiko Mizuno, Yuta Yamaguchi, Tomoki Mae, Yu Noda, Kamon Nakaya, Satoshi Nojima, Fuminori Sugihara, Daisuke Okuzaki, Masahito Ikawa, Shoichi Shimada, Sujin Kang, Atsushi Kumanogoh
Regulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis. Using genome-wide approaches
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Cortico-basal ganglia plasticity in motor learning Neuron (IF 14.7) Pub Date : 2024-07-12 Richard H. Roth, Jun B. Ding
One key function of the brain is to control our body’s movements, allowing us to interact with the world around us. Yet, many motor behaviors are not innate but require learning through repeated practice. Among the brain’s motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement
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SHIELD: Skull-shaped hemispheric implants enabling large-scale electrophysiology datasets in the mouse brain Neuron (IF 14.7) Pub Date : 2024-07-11 Corbett Bennett, Ben Ouellette, Tamina K. Ramirez, Alex Cahoon, Hannah Cabasco, Yoni Browning, Anna Lakunina, Galen F. Lynch, Ethan G. McBride, Hannah Belski, Ryan Gillis, Conor Grasso, Robert Howard, Tye Johnson, Henry Loeffler, Heston Smith, David Sullivan, Allison Williford, Shiella Caldejon, Severine Durand, Samuel Gale, Alan Guthrie, Vivian Ha, Warren Han, Ben Hardcastle, Chris Mochizuki, Arjun
To understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. Although new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe skull-shaped hemispheric implants enabling large-scale electrophysiology
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Sequence variations and accessory proteins adapt TMC functions to distinct sensory modalities Neuron (IF 14.7) Pub Date : 2024-07-09 Qiang Jiang, Wenjuan Zou, Shitian Li, Xufeng Qiu, Linhui Zhu, Lijun Kang, Ulrich Müller
Transmembrane channel-like (TMC) proteins are expressed throughout the animal kingdom and are thought to encode components of ion channels. Mammals express eight TMCs (mTMC1–8), two of which (mTMC1 and mTMC2) are subunits of mechanotransduction channels. expresses two TMCs (TMC-1 and TMC-2), which mediate mechanosensation, egg laying, and alkaline sensing. The mechanisms by which nematode TMCs contribute
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Embryonically active piriform cortex neurons promote intracortical recurrent connectivity during development Neuron (IF 14.7) Pub Date : 2024-07-03 David C. Wang, Fernando Santos-Valencia, Jun H. Song, Kevin M. Franks, Liqun Luo
Neuronal activity plays a critical role in the maturation of circuits that propagate sensory information into the brain. How widely does early activity regulate circuit maturation across the developing brain? Here, we used targeted recombination in active populations (TRAP) to perform a brain-wide survey for prenatally active neurons in mice and identified the piriform cortex as an abundantly TRAPed
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Mono-methylation of lysine 27 at histone 3 confers lifelong susceptibility to stress Neuron (IF 14.7) Pub Date : 2024-07-02 Angélica Torres-Berrío, Molly Estill, Vishwendra Patel, Aarthi Ramakrishnan, Hope Kronman, Angélica Minier-Toribio, Orna Issler, Caleb J. Browne, Eric M. Parise, Yentl Y. van der Zee, Deena M. Walker, Freddyson J. Martínez-Rivera, Casey K. Lardner, Romain Durand-de Cuttoli, Scott J. Russo, Li Shen, Simone Sidoli, Eric J. Nestler
Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed
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Short-latency preference for faces in primate superior colliculus depends on visual cortex Neuron (IF 14.7) Pub Date : 2024-07-02 Gongchen Yu, Leor N. Katz, Christian Quaia, Adam Messinger, Richard J. Krauzlis
Face processing is fundamental to primates and has been extensively studied in higher-order visual cortex. Here, we report that visual neurons in the midbrain superior colliculus (SC) of macaque monkeys display a preference for images of faces. This preference emerges within 40 ms of stimulus onset—well before “face patches” in visual cortex—and, at the population level, can be used to distinguish
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Cellular and circuit architecture of the lateral septum for reward processing Neuron (IF 14.7) Pub Date : 2024-07-02 Gaowei Chen, Shishi Lai, Shaolei Jiang, Fengling Li, Kaige Sun, Xiaocong Wu, Kuikui Zhou, Yutong Liu, Xiaofei Deng, Zijun Chen, Fang Xu, Yu Xu, Kunhua Wang, Gang Cao, Fuqiang Xu, Guo-Qiang Bi, Yingjie Zhu
The lateral septum (LS) is composed of heterogeneous cell types that are important for various motivated behaviors. However, the transcriptional profiles, spatial arrangement, function, and connectivity of these cell types have not been systematically studied. Using single-nucleus RNA sequencing, we delineated diverse genetically defined cell types in the LS that play distinct roles in reward processing
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Dynamic assemblies of parvalbumin interneurons in brain oscillations Neuron (IF 14.7) Pub Date : 2024-07-01 Yi-Chieh Huang, Hui-Ching Chen, Yu-Ting Lin, Szu-Ting Lin, Qinsi Zheng, Ahmed S. Abdelfattah, Luke D. Lavis, Eric R. Schreiter, Bei-Jung Lin, Tsai-Wen Chen
Brain oscillations are crucial for perception, memory, and behavior. Parvalbumin-expressing (PV) interneurons are critical for these oscillations, but their population dynamics remain unclear. Using voltage imaging, we simultaneously recorded membrane potentials in up to 26 PV interneurons during hippocampal ripple oscillations in mice. We found that PV cells generate ripple-frequency rhythms by forming
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Predictive sequence learning in the hippocampal formation Neuron (IF 14.7) Pub Date : 2024-06-24 Yusi Chen, Huanqiu Zhang, Mia Cameron, Terrence Sejnowski
The hippocampus receives sequences of sensory inputs from the cortex during exploration and encodes the sequences with millisecond precision. We developed a predictive autoencoder model of the hippocampus including the trisynaptic and monosynaptic circuits from the entorhinal cortex (EC). CA3 was trained as a self-supervised recurrent neural network to predict its next input. We confirmed that CA3
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Individual thalamic inhibitory interneurons are functionally specialized toward distinct visual features Neuron (IF 14.7) Pub Date : 2024-06-24 Fiona E. Müllner, Botond Roska
Inhibitory interneurons in the dorsolateral geniculate nucleus (dLGN) are situated at the first central synapse of the image-forming visual pathway, but little is known about their function. Given their anatomy, they are expected to be multiplexors, integrating many different retinal channels along their dendrites. Here, using targeted single-cell-initiated rabies tracing, we found that mouse dLGN
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A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation Neuron (IF 14.7) Pub Date : 2024-06-20 Jiayang Chen, Mary E. Lambo, Xia Ge, Joshua T. Dearborn, Yating Liu, Katherine B. McCullough, Raylynn G. Swift, Dora R. Tabachnick, Lucy Tian, Kevin Noguchi, Joel R. Garbow, John N. Constantino, Harrison W. Gabel, Keith B. Hengen, Susan E. Maloney, Joseph D. Dougherty
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Opto-seq reveals input-specific immediate-early gene induction in ventral tegmental area cell types Neuron (IF 14.7) Pub Date : 2024-06-19 Rhiana C. Simon, Mary C. Loveless, Joshua X. Yee, Brandon Goh, Su G. Cho, Zainab Nasir, Koichi Hashikawa, Garret D. Stuber, Larry S. Zweifel, Marta E. Soden
The ventral tegmental area (VTA) is a critical node in circuits governing motivated behavior and is home to diverse populations of neurons that release dopamine, gamma-aminobutyric acid (GABA), glutamate, or combinations of these neurotransmitters. The VTA receives inputs from many brain regions, but a comprehensive understanding of input-specific activation of VTA neuronal subpopulations is lacking
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Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy Neuron (IF 14.7) Pub Date : 2024-06-18 Jean Paul Chadarevian, Jonathan Hasselmann, Alina Lahian, Joia K. Capocchi, Adrian Escobar, Tau En Lim, Lauren Le, Christina Tu, Jasmine Nguyen, Sepideh Kiani Shabestari, William Carlen-Jones, Sunil Gandhi, Guojun Bu, David A. Hume, Clare Pridans, Zbigniew K. Wszolek, Robert C. Spitale, Hayk Davtyan, Mathew Blurton-Jones
Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate the diverse neuropathologies and reduced microglia numbers observed in patients. In this study, we generated a xenotolerant mouse model lacking the -intronic
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Microglia protect against age-associated brain pathologies Neuron (IF 14.7) Pub Date : 2024-06-18 David A.D. Munro, Nadine Bestard-Cuche, Conor McQuaid, Audrey Chagnot, Sepideh Kiani Shabestari, Jean Paul Chadarevian, Upasana Maheshwari, Stefan Szymkowiak, Kim Morris, Mehreen Mohammad, Andrea Corsinotti, Barry Bradford, Neil Mabbott, Ross J. Lennen, Maurits A. Jansen, Clare Pridans, Barry W. McColl, Annika Keller, Mathew Blurton-Jones, Axel Montagne, Anna Williams, Josef Priller
Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using the mouse model. In juvenile mice, we show that microglia are dispensable for the transcriptomic maturation of other brain cell types. By contrast, with advancing age, pathologies
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APP fragment controls both ionotropic and non-ionotropic signaling of NMDA receptors Neuron (IF 14.7) Pub Date : 2024-06-14 Jade Dunot, Sebastien Moreno, Carine Gandin, Paula A. Pousinha, Mascia Amici, Julien Dupuis, Margarita Anisimova, Alex Winschel, Magalie Uriot, Samuel J. Petshow, Maria Mensch, Ingrid Bethus, Camilla Giudici, Heike Hampel, Benedikt Wefers, Wolfgang Wurst, Ronald Naumann, Michael C. Ashby, Bodo Laube, Karen Zito, Jack R. Mellor, Laurent Groc, Michael Willem, Hélène Marie
NMDA receptors (NMDARs) are ionotropic receptors crucial for brain information processing. Yet, evidence also supports an ion-flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), an amyloid-β precursor protein (APP) cleavage product, as an NMDAR modulator with the unique dual regulatory capacity to impact both signaling modes
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A cerebellar granule cell-climbing fiber computation to learn to track long time intervals Neuron (IF 14.7) Pub Date : 2024-06-12 Martha G. Garcia-Garcia, Akash Kapoor, Oluwatobi Akinwale, Lina Takemaru, Tony Hyun Kim, Casey Paton, Ashok Litwin-Kumar, Mark J. Schnitzer, Liqun Luo, Mark J. Wagner
In classical cerebellar learning, Purkinje cells (PkCs) associate climbing fiber (CF) error signals with predictive granule cells (GrCs) that were active just prior (∼150 ms). The cerebellum also contributes to behaviors characterized by longer timescales. To investigate how GrC-CF-PkC circuits might learn seconds-long predictions, we imaged simultaneous GrC-CF activity over days of forelimb operant
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Making sense of Timothy syndrome with 3D human neuronal models Neuron (IF 14.7) Pub Date : 2024-06-05 Ramsey Najm, Juergen A. Knoblich
In a recent issue of Nature, Chen and colleagues1 reveal the potential for antisense oligonucleotides (ASOs) to rescue the neuropathological mechanisms underlying Timothy syndrome (TS) using three-dimensional neuronal models. Combining in vitro and in vivo approaches, the authors present a strategy to translate disease biology findings into potential therapeutics.
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From bile acids to melancholia Neuron (IF 14.7) Pub Date : 2024-06-05 Alexandra S. Klein, Mazen A. Kheirbek
In this issue of Neuron, Li, Zhang, et al.1 find that the bile acid receptor TGR5 in the lateral hypothalamus influences neuronal dynamics underlying stress-induced depression-like behaviors. Inhibition of these neurons produces antidepressant-like effects through a circuit that includes hippocampal CA3 and dorsolateral septum, revealing a novel potential therapeutic for depression.
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Seq-ing mechanisms behind types of Alzheimer’s disease Neuron (IF 14.7) Pub Date : 2024-06-05 Yun Chen, Jason D. Ulrich
Sporadic Alzheimer’s disease (AD) and autosomal dominant Alzheimer’s disease (ADAD) share pathological features, but differing mechanisms, leading to disease. In this issue of Neuron, Almeida, Eger, et al.1 uncovered molecular processes that may distinguish sporadic AD from ADAD and how the APOE-Christchurch variant may be protective.
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William A. Catterall (1946–2024) Neuron (IF 14.7) Pub Date : 2024-06-05 Todd Scheuer, Ruth Westenbroek, Ning Zheng, Franck Kalume, Thuy N. Vien, Jian Payandeh, Paul G. DeCaen
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Turning down the body heat: A novel mechanism for TRPV1 antagonist-induced hyperthermia Neuron (IF 14.7) Pub Date : 2024-06-05 Kali Esancy, Ajay Dhaka
While effective analgesics, TRPV1 antagonists can dangerously alter thermoregulation. In this issue of Neuron, Huang et al.1 demonstrate that interaction with the S4-S5 linker of TRPV1 determines whether an antagonist affects core body temperature, with promising implications for analgesic development.
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Imaging α-synuclein pathologies in animal models and patients with Parkinson’s and related diseases Neuron (IF 14.7) Pub Date : 2024-06-05 Hironobu Endo, Maiko Ono, Yuhei Takado, Kiwamu Matsuoka, Manami Takahashi, Kenji Tagai, Yuko Kataoka, Kosei Hirata, Keisuke Takahata, Chie Seki, Naomi Kokubo, Masayuki Fujinaga, Wakana Mori, Yuji Nagai, Koki Mimura, Katsushi Kumata, Tatsuya Kikuchi, Aki Shimozawa, Sushil K. Mishra, Yoshiki Yamaguchi, Hiroshi Shimizu, Akiyoshi Kakita, Hiroyuki Takuwa, Hitoshi Shinotoh, Hitoshi Shimada, Yasuyuki Kimura
Deposition of α-synuclein fibrils is implicated in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), while detection of α-synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing α-synuclein deposits in the brains of living subjects. optical and positron emission tomography (PET) imaging of mouse and marmoset
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Cell-class-specific electric field entrainment of neural activity Neuron (IF 14.7) Pub Date : 2024-06-04 Soo Yeun Lee, Konstantinos Kozalakis, Fahimeh Baftizadeh, Luke Campagnola, Tim Jarsky, Christof Koch, Costas A. Anastassiou
Electric fields affect the activity of neurons and brain circuits, yet how this happens at the cellular level remains enigmatic. Lack of understanding of how to stimulate the brain to promote or suppress specific activity significantly limits basic research and clinical applications. Here, we study how electric fields impact subthreshold and spiking properties of major cortical neuronal classes. We
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Cell-type-specific effects of age and sex on human cortical neurons Neuron (IF 14.7) Pub Date : 2024-06-04 Jo-Fan Chien, Hanqing Liu, Bang-An Wang, Chongyuan Luo, Anna Bartlett, Rosa Castanon, Nicholas D. Johnson, Joseph R. Nery, Julia Osteen, Junhao Li, Jordan Altshul, Mia Kenworthy, Cynthia Valadon, Michelle Liem, Naomi Claffey, Carolyn O'Connor, Luise A. Seeker, Joseph R. Ecker, M. Margarita Behrens, Eran A. Mukamel
Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons
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Principles of cortical areas and their implications for neuroimaging Neuron (IF 14.7) Pub Date : 2024-06-03 Steven E. Petersen, Benjamin A. Seitzman, Steven M. Nelson, Gagan S. Wig, Evan M. Gordon
Cortical organization should constrain the study of how the brain performs behavior and cognition. A fundamental concept in cortical organization is that of arealization: that the cortex is parceled into discrete areas. In part one of this report, we review how non-human animal studies have illuminated principles of cortical arealization by revealing: (1) what defines a cortical area, (2) how cortical
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Cryo-EM structures of pathogenic fibrils and their impact on neurodegenerative disease research Neuron (IF 14.7) Pub Date : 2024-06-03 Tiffany W. Todd, Naeyma N. Islam, Casey N. Cook, Thomas R. Caulfield, Leonard Petrucelli
Neurodegenerative diseases are commonly associated with the formation of aberrant protein aggregates within the brain, and ultrastructural analyses have revealed that the proteins within these inclusions often assemble into amyloid filaments. Cryoelectron microscopy (cryo-EM) has emerged as an effective method for determining the near-atomic structure of these disease-associated filamentous proteins
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Closed-loop microstimulations of the orbitofrontal cortex during real-life gaze interaction enhance dynamic social attention Neuron (IF 14.7) Pub Date : 2024-05-31 Siqi Fan, Olga Dal Monte, Amrita R. Nair, Nicholas A. Fagan, Steve W.C. Chang
Neurons from multiple prefrontal areas encode several key variables of social gaze interaction. To explore the causal roles of the primate prefrontal cortex in real-life gaze interaction, we applied weak closed-loop microstimulations that were precisely triggered by specific social gaze events. Microstimulations of the orbitofrontal cortex, but not the dorsomedial prefrontal cortex or the anterior
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Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist Neuron (IF 14.7) Pub Date : 2024-05-31 Alexandra Litvinchuk, Jung H. Suh, Jing L. Guo, Karin Lin, Sonnet S. Davis, Nga Bien-Ly, Eric Tycksen, G. Travis Tabor, Javier Remolina Serrano, Melissa Manis, Xin Bao, Choonghee Lee, Megan Bosch, Enmanuel J. Perez, Carla M. Yuede, Anil G. Cashikar, Jason D. Ulrich, Gilbert Di Paolo, David M. Holtzman
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Integrative multi-omic analysis reveals conserved cell-projection deficits in human Down syndrome brains Neuron (IF 14.7) Pub Date : 2024-05-28 Mohit Rastogi, Martina Bartolucci, Marina Nanni, Michelangelo Aloisio, Diego Vozzi, Andrea Petretto, Andrea Contestabile, Laura Cancedda
Down syndrome (DS) is the most common genetic cause of cognitive disability. However, it is largely unclear how triplication of a small gene subset may impinge on diverse aspects of DS brain physiopathology. Here, we took a multi-omic approach and simultaneously analyzed by RNA-seq and proteomics the expression signatures of two diverse regions of human postmortem DS brains. We found that the overexpression
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A neural circuit architecture for rapid learning in goal-directed navigation Neuron (IF 14.7) Pub Date : 2024-05-24 Chuntao Dan, Brad K. Hulse, Ramya Kappagantula, Vivek Jayaraman, Ann M. Hermundstad
Anchoring goals to spatial representations enables flexible navigation but is challenging in novel environments when both representations must be acquired simultaneously. We propose a framework for how uses internal representations of head direction (HD) to build goal representations upon selective thermal reinforcement. We show that flies use stochastically generated fixations and directed saccades
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Compensatory enhancement of input maintains aversive dopaminergic reinforcement in hungry Drosophila Neuron (IF 14.7) Pub Date : 2024-05-24 Eleonora Meschi, Lucille Duquenoy, Nils Otto, Georgia Dempsey, Scott Waddell
Hungry animals need compensatory mechanisms to maintain flexible brain function, while modulation reconfigures circuits to prioritize resource seeking. In , hunger inhibits aversively reinforcing dopaminergic neurons (DANs) to permit the expression of food-seeking memories. Multitasking the reinforcement system for motivation potentially undermines aversive learning. We find that chronic hunger mildly
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Neurobiological basis of stress resilience Neuron (IF 14.7) Pub Date : 2024-05-24 Eric J. Nestler, Scott J. Russo
A majority of humans faced with severe stress maintain normal physiological and behavioral function, a process referred to as resilience. Such stress resilience has been modeled in laboratory animals and, over the past 15 years, has transformed our understanding of stress responses and how to approach the treatment of human stress disorders such as depression, post-traumatic stress disorder (PTSD)
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What’s the n? On sample size vs. subject number for brain-behavior neurophysiology and neuromodulation Neuron (IF 14.7) Pub Date : 2024-05-22 Wael F. Asaad, Sameer A. Sheth
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Long-wavelength traveling waves of vasomotion modulate the perfusion of cortex Neuron (IF 14.7) Pub Date : 2024-05-22 Thomas Broggini, Jacob Duckworth, Xiang Ji, Rui Liu, Xinyue Xia, Philipp Mächler, Iftach Shaked, Leon Paul Munting, Satish Iyengar, Michael Kotlikoff, Susanne J. van Veluw, Massimo Vergassola, Gal Mishne, David Kleinfeld
Brain arterioles are active, multicellular complexes whose diameters oscillate at ∼ 0.1 Hz. We assess the physiological impact and spatiotemporal dynamics of vaso-oscillations in the awake mouse. First, vaso-oscillations in penetrating arterioles, which source blood from pial arterioles to the capillary bed, profoundly impact perfusion throughout neocortex. The modulation in flux during resting-state
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The behavioral relevance of a modular organization in the lateral habenula Neuron (IF 14.7) Pub Date : 2024-05-20 Leo Michel, Patricia Molina, Manuel Mameli
Behavioral strategies for survival rely on the updates the brain continuously makes based on the surrounding environment. External stimuli—neutral, positive, and negative—relay core information to the brain, where a complex anatomical network rapidly organizes actions, including approach or escape, and regulates emotions. Human neuroimaging and physiology in nonhuman primates, rodents, and teleosts
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Threat-dependent scaling of prelimbic dynamics to enhance fear representation Neuron (IF 14.7) Pub Date : 2024-05-20 José Patricio Casanova, Clément Pouget, Nadja Treiber, Ishaant Agarwal, Mark Allen Brimble, Gisella Vetere
Promptly identifying threatening stimuli is crucial for survival. Freezing is a natural behavior displayed by rodents toward potential or actual threats. Although it is known that the prelimbic cortex (PL) is involved in both risk evaluation and in fear and anxiety-like behavior expression, here we explored whether PL neuronal activity can dynamically represent different internal states of the same
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Thriving in neuroscience careers: Three lessons from 12+ years of the BRAINS Program Neuron (IF 14.7) Pub Date : 2024-05-20 Joyce W. Yen, M. Claire Horner-Devine, Erin Carll, Rachel Talney, Sheri J.Y. Mizumori
The NINDS-funded BRAINS Program for neuroscientists from underrepresented and marginalized groups has positively impacted its participants and the field. We discuss three lessons to advance excellence and diversity: center relationships, provide ongoing engagement, and leverage programmatic expertise.
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Nuclear aggregates of NONO/SFPQ and A-to-I-edited RNA in Parkinson’s disease and dementia with Lewy bodies Neuron (IF 14.7) Pub Date : 2024-05-17 Nandkishore R. Belur, Bernabe I. Bustos, Steven J. Lubbe, Joseph R. Mazzulli
Neurodegenerative diseases are commonly classified as proteinopathies that are defined by the aggregation of a specific protein. Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are classified as synucleinopathies since α-synuclein (α-syn)-containing inclusions histopathologically define these diseases. Unbiased biochemical analysis of PD and DLB patient material unexpectedly revealed novel
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Distinct feedforward and feedback pathways for cell-type specific attention effects Neuron (IF 14.7) Pub Date : 2024-05-16 Georgios Spyropoulos, Marius Schneider, Jochem van Kempen, Marc Alwin Gieselmann, Alexander Thiele, Martin Vinck
Selective attention is thought to depend on enhanced firing activity in extrastriate areas. Theories suggest that this enhancement depends on selective inter-areal communication via gamma (30–80 Hz) phase-locking. To test this, we simultaneously recorded from different cell types and cortical layers of macaque V1 and V4. We find that while V1-V4 gamma phase-locking between local field potentials increases
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Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins Neuron (IF 14.7) Pub Date : 2024-05-16 Lulu Y. Chen, Man Jiang, Bo Zhang, Ozgun Gokce, Thomas C. Südhof