journal
https://read.qxmd.com/read/38382521/tuned-geometries-of-hippocampal-representations-meet-the-computational-demands-of-social-memory
#21
JOURNAL ARTICLE
Lara M Boyle, Lorenzo Posani, Sarah Irfan, Steven A Siegelbaum, Stefano Fusi
Social memory consists of two processes: the detection of familiar compared with novel conspecifics and the detailed recollection of past social episodes. We investigated the neural bases for these processes using calcium imaging of dorsal CA2 hippocampal pyramidal neurons, known to be important for social memory, during social/spatial encounters with novel conspecifics and familiar littermates. Whereas novel individuals were represented in a low-dimensional geometry that allows for generalization of social identity across different spatial locations and of location across different identities, littermates were represented in a higher-dimensional geometry that supports high-capacity memory storage...
February 15, 2024: Neuron
https://read.qxmd.com/read/38377989/cell-type-specific-expression-of-trnas-in-the-brain-regulates-cellular-homeostasis
#22
JOURNAL ARTICLE
Mridu Kapur, Michael J Molumby, Carlos Guzman, Sven Heinz, Susan L Ackerman
Defects in tRNA biogenesis are associated with multiple neurological disorders, yet our understanding of these diseases has been hampered by an inability to determine tRNA expression in individual cell types within a complex tissue. Here, we developed a mouse model in which RNA polymerase III is conditionally epitope tagged in a Cre-dependent manner, allowing us to accurately profile tRNA expression in any cell type in vivo. We investigated tRNA expression in diverse nervous system cell types, revealing dramatic heterogeneity in the expression of tRNA genes between populations...
February 15, 2024: Neuron
https://read.qxmd.com/read/38402606/mechanisms-of-sex-differences-in-alzheimer-s-disease
#23
REVIEW
Chloe Lopez-Lee, Eileen Ruth S Torres, Gillian Carling, Li Gan
Alzheimer's disease (AD) and the mechanisms underlying its etiology and progression are complex and multifactorial. The higher AD risk in women may serve as a clue to better understand these complicated processes. In this review, we examine aspects of AD that demonstrate sex-dependent effects and delve into the potential biological mechanisms responsible, compiling findings from advanced technologies such as single-cell RNA sequencing, metabolomics, and multi-omics analyses. We review evidence that sex hormones and sex chromosomes interact with various disease mechanisms during aging, encompassing inflammation, metabolism, and autophagy, leading to unique characteristics in disease progression between men and women...
February 13, 2024: Neuron
https://read.qxmd.com/read/38377990/sustained-antidepressant-effects-of-ketamine-metabolite-involve-gabaergic-inhibition-mediated-molecular-dynamics-in-apvt-glutamatergic-neurons
#24
JOURNAL ARTICLE
Ayako Kawatake-Kuno, Haiyan Li, Hiromichi Inaba, Momoka Hikosaka, Erina Ishimori, Takatoshi Ueki, Yury Garkun, Hirofumi Morishita, Shuh Narumiya, Naoya Oishi, Gen Ohtsuki, Toshiya Murai, Shusaku Uchida
Despite the rapid and sustained antidepressant effects of ketamine and its metabolites, their underlying cellular and molecular mechanisms are not fully understood. Here, we demonstrate that the sustained antidepressant-like behavioral effects of (2S,6S)-hydroxynorketamine (HNK) in repeatedly stressed animal models involve neurobiological changes in the anterior paraventricular nucleus of the thalamus (aPVT). Mechanistically, (2S,6S)-HNK induces mRNA expression of extrasynaptic GABAA receptors and subsequently enhances GABAA -receptor-mediated tonic currents, leading to the nuclear export of histone demethylase KDM6 and its replacement by histone methyltransferase EZH2...
February 9, 2024: Neuron
https://read.qxmd.com/read/38359826/episodic-memory-development-bridging-animal-and-human-research
#25
REVIEW
Juraj Bevandić, Loïc J Chareyron, Jocelyne Bachevalier, Francesca Cacucci, Lisa Genzel, Nora S Newcombe, Faraneh Vargha-Khadem, H Freyja Ólafsdóttir
Human episodic memory is not functionally evident until about 2 years of age and continues to develop into the school years. Behavioral studies have elucidated this developmental timeline and its constituent processes. In tandem, lesion and neurophysiological studies in non-human primates and rodents have identified key neural substrates and circuit mechanisms that may underlie episodic memory development. Despite this progress, collaborative efforts between psychologists and neuroscientists remain limited, hindering progress...
February 9, 2024: Neuron
https://read.qxmd.com/read/38359827/cell-type-specific-optogenetic-fmri-on-basal-forebrain-reveals-functional-network-basis-of-behavioral-preference
#26
JOURNAL ARTICLE
Yijuan Zou, Chuanjun Tong, Wanling Peng, Yue Qiu, Jiangxue Li, Ying Xia, Mengchao Pei, Kaiwei Zhang, Weishuai Li, Min Xu, Zhifeng Liang
The basal forebrain (BF) is a complex structure that plays key roles in regulating various brain functions. However, it remains unclear how cholinergic and non-cholinergic BF neurons modulate large-scale functional networks and their relevance in intrinsic and extrinsic behaviors. With an optimized awake mouse optogenetic fMRI approach, we revealed that optogenetic stimulation of four BF neuron types evoked distinct cell-type-specific whole-brain BOLD activations, which could be attributed to BF-originated low-dimensional structural networks...
February 7, 2024: Neuron
https://read.qxmd.com/read/38340718/data-science-opportunities-of-large-language-models-for-neuroscience-and-biomedicine
#27
REVIEW
Danilo Bzdok, Andrew Thieme, Oleksiy Levkovskyy, Paul Wren, Thomas Ray, Siva Reddy
Large language models (LLMs) are a new asset class in the machine-learning landscape. Here we offer a primer on defining properties of these modeling techniques. We then reflect on new modes of investigation in which LLMs can be used to reframe classic neuroscience questions to deliver fresh answers. We reason that LLMs have the potential to (1) enrich neuroscience datasets by adding valuable meta-information, such as advanced text sentiment, (2) summarize vast information sources to overcome divides between siloed neuroscience communities, (3) enable previously unthinkable fusion of disparate information sources relevant to the brain, (4) help deconvolve which cognitive concepts most usefully grasp phenomena in the brain, and much more...
February 7, 2024: Neuron
https://read.qxmd.com/read/38366598/targeting-14-3-3%C3%AE-mediated-tdp-43-pathology-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-mice
#28
JOURNAL ARTICLE
Yazi D Ke, Annika van Hummel, Carol Au, Gabriella Chan, Wei Siang Lee, Julia van der Hoven, Magdalena Przybyla, Yuanyuan Deng, Miheer Sabale, Nicolle Morey, Josefine Bertz, Astrid Feiten, Stefania Ippati, Claire H Stevens, Shu Yang, Amadeus Gladbach, Nikolas K Haass, Jillian J Kril, Ian P Blair, Fabien Delerue, Lars M Ittner
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by cytoplasmic deposition of the nuclear TAR-binding protein 43 (TDP-43). Although cytoplasmic re-localization of TDP-43 is a key event in the pathogenesis of ALS/FTD, the underlying mechanisms remain unknown. Here, we identified a non-canonical interaction between 14-3-3θ and TDP-43, which regulates nuclear-cytoplasmic shuttling. Neuronal 14-3-3θ levels were increased in sporadic ALS and FTD with TDP-43 pathology...
February 6, 2024: Neuron
https://read.qxmd.com/read/38359825/asics-mediate-fast-excitatory-synaptic-transmission-for-tactile-discrimination
#29
JOURNAL ARTICLE
Akihiro Yamada, Jennifer Ling, Ayaka I Yamada, Hidemasa Furue, Jianguo G Gu
Tactile discrimination, the ability to differentiate objects' physical properties such as texture, shape, and edges, is essential for environmental exploration, social interaction, and early childhood development. This ability heavily relies on Merkel cell-neurite complexes (MNCs), the tactile end-organs enriched in the fingertips of humans and the whisker hair follicles of non-primate mammals. Although recent studies have advanced our knowledge on mechanical transduction in MNCs, it remains unknown how tactile signals are encoded at MNCs...
February 6, 2024: Neuron
https://read.qxmd.com/read/38354737/anterior-cingulate-cortex-projections-to-the-dorsal-medial-striatum-underlie-insomnia-associated-with-chronic-pain
#30
JOURNAL ARTICLE
Ya-Dong Li, Yan-Jia Luo, Wei-Kun Su, Jing Ge, Andrew Crowther, Ze-Ka Chen, Lu Wang, Michael Lazarus, Zi-Long Liu, Wei-Min Qu, Zhi-Li Huang
Chronic pain often leads to the development of sleep disturbances. However, the precise neural circuit mechanisms responsible for sleep disorders in chronic pain have remained largely unknown. Here, we present compelling evidence that hyperactivity of pyramidal neurons (PNs) in the anterior cingulate cortex (ACC) drives insomnia in a mouse model of nerve-injury-induced chronic pain. After nerve injury, ACC PNs displayed spontaneous hyperactivity selectively in periods of insomnia. We then show that ACC PNs were both necessary for developing chronic-pain-induced insomnia and sufficient to mimic sleep loss in naive mice...
January 31, 2024: Neuron
https://read.qxmd.com/read/38340719/epigenetic-dysregulation-in-alzheimer-s-disease-peripheral-immunity
#31
JOURNAL ARTICLE
Abhirami Ramakrishnan, Natalie Piehl, Brooke Simonton, Milan Parikh, Ziyang Zhang, Victoria Teregulova, Lynn van Olst, David Gate
The peripheral immune system in Alzheimer's disease (AD) has not been thoroughly studied with modern sequencing methods. To investigate epigenetic and transcriptional alterations to the AD peripheral immune system, we used single-cell sequencing strategies, including assay for transposase-accessible chromatin and RNA sequencing. We reveal a striking amount of open chromatin in peripheral immune cells in AD. In CD8 T cells, we uncover a cis-regulatory DNA element co-accessible with the CXC motif chemokine receptor 3 gene promoter...
January 31, 2024: Neuron
https://read.qxmd.com/read/38295790/clearance-of-%C3%AE-amyloid-and-synapses-by-the-optogenetic-depolarization-of-microglia-is-complement-selective
#32
JOURNAL ARTICLE
Zezhong Lv, Lixi Chen, Ping Chen, Huipai Peng, Yi Rong, Wei Hong, Qiang Zhou, Nan Li, Boxing Li, Rosa C Paolicelli, Yang Zhan
Microglia actively monitor the neighboring brain microenvironments and constantly contact synapses with their unique ramified processes. In neurodegenerative diseases, including Alzheimer's disease (AD), microglia undergo morphological and functional alterations. Whether the direct manipulation of microglia can selectively or concurrently modulate synaptic function and the response to disease-associated factors remains elusive. Here, we employ optogenetic methods to stimulate microglia in vitro and in vivo...
January 30, 2024: Neuron
https://read.qxmd.com/read/38301647/apoe-loss-of-function-variants-compatible-with-longevity-and-associated-with-resistance-to-alzheimer-s-disease-pathology
#33
JOURNAL ARTICLE
Augustine Chemparathy, Yann Le Guen, Sunny Chen, Eun-Gyung Lee, Lesley Leong, John E Gorzynski, Tanner D Jensen, Alexis Ferrasse, Guangxue Xu, Hong Xiang, Michael E Belloy, Nandita Kasireddy, Andrés Peña-Tauber, Kennedy Williams, Ilaria Stewart, Lia Talozzi, Thomas S Wingo, James J Lah, Suman Jayadev, Chadwick M Hales, Elaine Peskind, Daniel D Child, Sigrun Roeber, C Dirk Keene, Le Cong, Euan A Ashley, Chang-En Yu, Michael D Greicius
The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants. Five carriers were controls (aged 71-90 years), one carrier was affected by progressive supranuclear palsy, and one carrier was affected by AD with an unremarkable age at onset of 75 years...
January 29, 2024: Neuron
https://read.qxmd.com/read/38295791/the-mediodorsal-thalamus-in-executive-control
#34
REVIEW
Mathieu Wolff, Michael M Halassa
Executive control, the ability to organize thoughts and action plans in real time, is a defining feature of higher cognition. Classical theories have emphasized cortical contributions to this process, but recent studies have reinvigorated interest in the role of the thalamus. Although it is well established that local thalamic damage diminishes cognitive capacity, such observations have been difficult to inform functional models. Recent progress in experimental techniques is beginning to enrich our understanding of the anatomical, physiological, and computational substrates underlying thalamic engagement in executive control...
January 25, 2024: Neuron
https://read.qxmd.com/read/38301648/a-role-for-the-cerebellum-in-motor-triggered-alleviation-of-anxiety
#35
JOURNAL ARTICLE
Xiao-Yang Zhang, Wen-Xia Wu, Li-Ping Shen, Miao-Jin Ji, Peng-Fei Zhao, Lei Yu, Jun Yin, Shu-Tao Xie, Yun-Yong Xie, Yang-Xun Zhang, Hong-Zhao Li, Qi-Peng Zhang, Chao Yan, Fei Wang, Chris I De Zeeuw, Jian-Jun Wang, Jing-Ning Zhu
Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect...
January 23, 2024: Neuron
https://read.qxmd.com/read/38295792/the-calmodulin-interacting-peptide-pcp4a-regulates-feeding-state-dependent-behavioral-choice-in-zebrafish
#36
JOURNAL ARTICLE
Margherita Zaupa, Nagarjuna Nagaraj, Anna Sylenko, Herwig Baier, Suphansa Sawamiphak, Alessandro Filosa
Animals constantly need to judge the valence of an object in their environment: is it potential food or a threat? The brain makes fundamental decisions on the appropriate behavioral strategy by integrating external information from sensory organs and internal signals related to physiological needs. For example, a hungry animal may take more risks than a satiated one when deciding to approach or avoid an object. Using a proteomic profiling approach, we identified the Calmodulin-interacting peptide Pcp4a as a key regulator of foraging-related decisions...
January 23, 2024: Neuron
https://read.qxmd.com/read/38290518/physical-and-functional-convergence-of-the-autism-risk-genes-scn2a-and-ank2-in-neocortical-pyramidal-cell-dendrites
#37
JOURNAL ARTICLE
Andrew D Nelson, Amanda M Catalfio, Julie P Gupta, Lia Min, René N Caballero-Florán, Kendall P Dean, Carina C Elvira, Kimberly D Derderian, Henry Kyoung, Atehsa Sahagun, Stephan J Sanders, Kevin J Bender, Paul M Jenkins
Dysfunction in sodium channels and their ankyrin scaffolding partners have both been implicated in neurodevelopmental disorders, including autism spectrum disorder (ASD). In particular, the genes SCN2A, which encodes the sodium channel NaV 1.2, and ANK2, which encodes ankyrin-B, have strong ASD association. Recent studies indicate that ASD-associated haploinsufficiency in Scn2a impairs dendritic excitability and synaptic function in neocortical pyramidal cells, but how NaV 1.2 is anchored within dendritic regions is unknown...
January 23, 2024: Neuron
https://read.qxmd.com/read/38290517/advances-in-structure-based-drug-design-the-potential-for-precision-therapeutics-in-psychiatric-disorders
#38
REVIEW
Dongmei Cao, Pei Zhang, Sheng Wang
Over the years, the field of GPCR drug design has undergone a remarkable evolution, fueled by advancements in science and technology. This evolution has given rise to a diverse range of ideas and approaches in structure-based drug design, bolstering the versatility and strength of the GPCR drug design toolbox. This review encapsulates the iterative development process, navigating challenges and opportunities in structure-based drug design within GPCRs. With a focused emphasis on its impact on psychiatric disorders, the review accentuates recent advancements and delves into the potentials unlocked by emerging technologies...
January 23, 2024: Neuron
https://read.qxmd.com/read/38290516/single-neuron-projectomes-of-mouse-paraventricular-hypothalamic-nucleus-oxytocin-neurons-reveal-mutually-exclusive-projection-patterns
#39
JOURNAL ARTICLE
Humingzhu Li, Tao Jiang, Sile An, Mingrui Xu, Lingfeng Gou, Biyu Ren, Xiaoxue Shi, Xiaofei Wang, Jun Yan, Jing Yuan, Xiaohong Xu, Qing-Feng Wu, Qingming Luo, Hui Gong, Wen-Jie Bian, Anan Li, Xiang Yu
Oxytocin (OXT) plays important roles in autonomic control and behavioral modulation. However, it is unknown how the projection patterns of OXT neurons align with underlying physiological functions. Here, we present the reconstructed single-neuron, whole-brain projectomes of 264 OXT neurons of the mouse paraventricular hypothalamic nucleus (PVH) at submicron resolution. These neurons hierarchically clustered into two groups, with distinct morphological and transcriptional characteristics and mutually exclusive projection patterns...
January 23, 2024: Neuron
https://read.qxmd.com/read/38278147/glutamate-inputs-send-prediction-error-of-reward-but-not-negative-value-of-aversive-stimuli-to-dopamine-neurons
#40
JOURNAL ARTICLE
Ryunosuke Amo, Naoshige Uchida, Mitsuko Watabe-Uchida
Midbrain dopamine neurons are thought to signal reward prediction errors (RPEs), but the mechanisms underlying RPE computation, particularly the contributions of different neurotransmitters, remain poorly understood. Here, we used a genetically encoded glutamate sensor to examine the pattern of glutamate inputs to dopamine neurons in mice. We found that glutamate inputs exhibit virtually all of the characteristics of RPE rather than conveying a specific component of RPE computation, such as reward or expectation...
January 22, 2024: Neuron
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