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A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice 嗅球中的 GnRH 神经元群将雄性小鼠的社会相关气味转化为生殖行为
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-08-02 DOI: 10.1038/s41593-024-01724-1
Laurine Decoster, Sara Trova, Stefano Zucca, Janice Bulk, Ayden Gouveia, Gaetan Ternier, Tori Lhomme, Amandine Legrand, Sarah Gallet, Ulrich Boehm, Amanda Wyatt, Vanessa Wahl, Philipp Wartenberg, Erik Hrabovszky, Gergely Rácz, Federico Luzzati, Giulia Nato, Marco Fogli, Paolo Peretto, Sonja C. Schriever, Miriam Bernecker, Paul T. Pfluger, Sophie M. Steculorum, Serena Bovetti, Sowmyalakshmi Rasika, Vincent Prevot, Mauro S. B. Silva, Paolo Giacobini
{"title":"A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice","authors":"Laurine Decoster, Sara Trova, Stefano Zucca, Janice Bulk, Ayden Gouveia, Gaetan Ternier, Tori Lhomme, Amandine Legrand, Sarah Gallet, Ulrich Boehm, Amanda Wyatt, Vanessa Wahl, Philipp Wartenberg, Erik Hrabovszky, Gergely Rácz, Federico Luzzati, Giulia Nato, Marco Fogli, Paolo Peretto, Sonja C. Schriever, Miriam Bernecker, Paul T. Pfluger, Sophie M. Steculorum, Serena Bovetti, Sowmyalakshmi Rasika, Vincent Prevot, Mauro S. B. Silva, Paolo Giacobini","doi":"10.1038/s41593-024-01724-1","DOIUrl":"10.1038/s41593-024-01724-1","url":null,"abstract":"Hypothalamic gonadotropin-releasing hormone (GnRH) neurons regulate fertility and integrate hormonal status with environmental cues to ensure reproductive success. Here we show that GnRH neurons in the olfactory bulb (GnRHOB) of adult mice can mediate social recognition. Specifically, we show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the median eminence. GnRHOB neurons in males express vomeronasal and olfactory receptors, are activated by female odors and mediate gonadotropin release in response to female urine. Male preference for female odors required the presence and activation of GnRHOB neurons, was impaired after genetic inhibition or ablation of these cells and relied on GnRH signaling in the posterodorsal medial amygdala. GnRH receptor expression in amygdala kisspeptin neurons appear to be required for GnRHOB neurons’ actions on male mounting behavior. Taken together, these results establish GnRHOB neurons as regulating fertility, sex recognition and mating in male mice. Studying GnRH neuroendocrine cells in the mouse olfactory bulb (GnRHOB neurons), Decoster et al. show that these cells respond to female odors and their activation regulates males’ female-odor preference and mating behavior.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Population-level coding of avoidance learning in medial prefrontal cortex 内侧前额叶皮层中回避学习的群体级编码
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-29 DOI: 10.1038/s41593-024-01704-5
Benjamin Ehret, Roman Boehringer, Elizabeth A. Amadei, Maria R. Cervera, Christian Henning, Aniruddh R. Galgali, Valerio Mante, Benjamin F. Grewe
{"title":"Population-level coding of avoidance learning in medial prefrontal cortex","authors":"Benjamin Ehret, Roman Boehringer, Elizabeth A. Amadei, Maria R. Cervera, Christian Henning, Aniruddh R. Galgali, Valerio Mante, Benjamin F. Grewe","doi":"10.1038/s41593-024-01704-5","DOIUrl":"10.1038/s41593-024-01704-5","url":null,"abstract":"The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a new tone-signaled active avoidance paradigm in mice. We developed an analysis approach based on dimensionality reduction and decoding that allowed us to identify interpretable task-related population activity patterns. While a large fraction of tone-evoked activity was not informative about behavior execution, we identified an activity pattern that was predictive of tone-induced avoidance actions and did not occur for spontaneous actions with similar motion kinematics. Moreover, this avoidance-specific activity differed between distinct avoidance actions learned in two consecutive tasks. Overall, our results are consistent with a model in which mPFC contributes to the selection of goal-directed actions by transforming sensory inputs into specific behavioral outputs through distributed population-level computations. Ehret et al. uncover neural activity patterns in the prefrontal cortex that link sensory stimuli to learned behavioral responses by isolating interpretable activity patterns that are shared among mice performing the same task.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01704-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Centering cognitive neuroscience on task demands and generalization 认知神经科学以任务需求和推广为中心
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-29 DOI: 10.1038/s41593-024-01711-6
Matthias Nau, Alexandra C. Schmid, Simon M. Kaplan, Chris I. Baker, Dwight J. Kravitz
{"title":"Centering cognitive neuroscience on task demands and generalization","authors":"Matthias Nau, Alexandra C. Schmid, Simon M. Kaplan, Chris I. Baker, Dwight J. Kravitz","doi":"10.1038/s41593-024-01711-6","DOIUrl":"10.1038/s41593-024-01711-6","url":null,"abstract":"Cognitive neuroscience seeks generalizable theories explaining the relationship between behavioral, physiological and mental states. In pursuit of such theories, we propose a theoretical and empirical framework that centers on understanding task demands and the mutual constraints they impose on behavior and neural activity. Task demands emerge from the interaction between an agent’s sensory impressions, goals and behavior, which jointly shape the activity and structure of the nervous system on multiple spatiotemporal scales. Understanding this interaction requires multitask studies that vary more than one experimental component (for example, stimuli and instructions) combined with dense behavioral and neural sampling and explicit testing for generalization across tasks and data modalities. By centering task demands rather than mental processes that tasks are assumed to engage, this framework paves the way for the discovery of new generalizable concepts unconstrained by existing taxonomies, and moves cognitive neuroscience toward an action-oriented, dynamic and integrated view of the brain. Task demands are a primary determiner of behavior and neurophysiology. Here the authors discuss how understanding their influence through multitask studies and tests of generalization is the key to articulating novel cognitive neuroscience concepts.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Explaining dopamine through prediction errors and beyond 通过预测误差及其他因素解释多巴胺。
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-25 DOI: 10.1038/s41593-024-01705-4
Samuel J. Gershman, John A. Assad, Sandeep Robert Datta, Scott W. Linderman, Bernardo L. Sabatini, Naoshige Uchida, Linda Wilbrecht
{"title":"Explaining dopamine through prediction errors and beyond","authors":"Samuel J. Gershman, John A. Assad, Sandeep Robert Datta, Scott W. Linderman, Bernardo L. Sabatini, Naoshige Uchida, Linda Wilbrecht","doi":"10.1038/s41593-024-01705-4","DOIUrl":"10.1038/s41593-024-01705-4","url":null,"abstract":"The most influential account of phasic dopamine holds that it reports reward prediction errors (RPEs). The RPE-based interpretation of dopamine signaling is, in its original form, probably too simple and fails to explain all the properties of phasic dopamine observed in behaving animals. This Perspective helps to resolve some of the conflicting interpretations of dopamine that currently exist in the literature. We focus on the following three empirical challenges to the RPE theory of dopamine: why does dopamine (1) ramp up as animals approach rewards, (2) respond to sensory and motor features and (3) influence action selection? We argue that the prediction error concept, once it has been suitably modified and generalized based on an analysis of each computational problem, answers each challenge. Nonetheless, there are a number of additional empirical findings that appear to demand fundamentally different theoretical explanations beyond encoding RPE. Therefore, looking forward, we discuss the prospects for a unifying theory that respects the diversity of dopamine signaling and function as well as the complex circuitry that both underlies and responds to dopaminergic transmission. The hypothesis that dopamine reports reward prediction errors has been both influential and controversial. This Perspective characterizes the present state of evidence, indicating where it succeeds and where it falls short. A complete account of dopamine will probably need to move beyond the reward prediction error hypothesis while retaining its core explanatory power.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Author Correction: Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane 作者更正:转基因胸膜小鼠耳蜗调谐能力增强
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-24 DOI: 10.1038/s41593-024-01727-y
Ian J. Russell, P. Kevin Legan, Victoria A. Lukashkina, Andrei N. Lukashkin, Richard J. Goodyear, Guy P. Richardson
{"title":"Author Correction: Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane","authors":"Ian J. Russell, P. Kevin Legan, Victoria A. Lukashkina, Andrei N. Lukashkin, Richard J. Goodyear, Guy P. Richardson","doi":"10.1038/s41593-024-01727-y","DOIUrl":"10.1038/s41593-024-01727-y","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01727-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nested compressed co-representations of multiple sequential experiences during sleep 睡眠中多重连续经验的嵌套压缩共表征
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-19 DOI: 10.1038/s41593-024-01703-6
Kefei Liu, Jeremie Sibille, George Dragoi
{"title":"Nested compressed co-representations of multiple sequential experiences during sleep","authors":"Kefei Liu, Jeremie Sibille, George Dragoi","doi":"10.1038/s41593-024-01703-6","DOIUrl":"10.1038/s41593-024-01703-6","url":null,"abstract":"Animals encounter and remember multiple experiences daily. During sleep, hippocampal neuronal ensembles replay past experiences and preplay future ones. Although most previous studies investigated p/replay of a single experience, it remains unclear how the hippocampus represents many experiences without major interference during sleep. By monitoring hippocampal neuronal ensembles as rats encountered 15 distinct linear track experiences, we uncovered principles for efficient multi-experience compressed p/replay representation. First, we found a serial position effect whereby the earliest and the most recent experiences had the strongest representations. Second, distinct experiences were co-represented in a multiplexed, flickering manner during nested p/replay events, which greatly enhanced the network’s representational capacity. Third, spatially contiguous and disjunct track pairs were bound together into contiguous conjunctive representations during sleep. Finally, sequences spanning day-long multi-track experiences were p/replayed at hyper-compressed ratios during sleep. These coding schemes efficiently parallelize, bind and compress multiple sequential representations with reduced interference and enhanced capacity during sleep. Liu et al. unraveled several hippocampal neural ensemble coding schemes that efficiently represent numerous daily experiences during sleep by prioritizing the most recent and earliest events, multiplexing co-representations and compressing day-long sequences.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Higher-order interactions between hippocampal CA1 neurons are disrupted in amnestic mice 失忆症小鼠海马 CA1 神经元之间的高阶交互作用受到破坏
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-19 DOI: 10.1038/s41593-024-01713-4
Chen Yan, Valentina Mercaldo, Alexander D. Jacob, Emily Kramer, Andrew Mocle, Adam I. Ramsaran, Lina Tran, Asim J. Rashid, Sungmo Park, Nathan Insel, A. David Redish, Paul W. Frankland, Sheena A. Josselyn
{"title":"Higher-order interactions between hippocampal CA1 neurons are disrupted in amnestic mice","authors":"Chen Yan, Valentina Mercaldo, Alexander D. Jacob, Emily Kramer, Andrew Mocle, Adam I. Ramsaran, Lina Tran, Asim J. Rashid, Sungmo Park, Nathan Insel, A. David Redish, Paul W. Frankland, Sheena A. Josselyn","doi":"10.1038/s41593-024-01713-4","DOIUrl":"10.1038/s41593-024-01713-4","url":null,"abstract":"Across systems, higher-order interactions between components govern emergent dynamics. Here we tested whether contextual threat memory retrieval in mice relies on higher-order interactions between dorsal CA1 hippocampal neurons requiring learning-induced dendritic spine plasticity. We compared population-level Ca2+ transients as wild-type mice (with intact learning-induced spine plasticity and memory) and amnestic mice (TgCRND8 mice with high levels of amyloid-β and deficits in learning-induced spine plasticity and memory) were tested for memory. Using machine-learning classifiers with different capacities to use input data with complex interactions, our findings indicate complex neuronal interactions in the memory representation of wild-type, but not amnestic, mice. Moreover, a peptide that partially restored learning-induced spine plasticity also restored the statistical complexity of the memory representation and memory behavior in Tg mice. These findings provide a previously missing bridge between levels of analysis in memory research, linking receptors, spines, higher-order neuronal dynamics and behavior. Coordinated neuronal activity may mediate memory in hippocampal CA1. Here, the authors use an array of machine-learning classifiers to reveal how higher-order population dynamics and learning-induced spine plasticity are disrupted in amnestic mice.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice 小鼠星形胶质细胞需要神经元周围网来维持突触平衡
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-17 DOI: 10.1038/s41593-024-01714-3
Bhanu P. Tewari, AnnaLin M. Woo, Courtney E. Prim, Lata Chaunsali, Dipan C. Patel, Ian F. Kimbrough, Kaliroi Engel, Jack L. Browning, Susan L. Campbell, Harald Sontheimer
{"title":"Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice","authors":"Bhanu P. Tewari, AnnaLin M. Woo, Courtney E. Prim, Lata Chaunsali, Dipan C. Patel, Ian F. Kimbrough, Kaliroi Engel, Jack L. Browning, Susan L. Campbell, Harald Sontheimer","doi":"10.1038/s41593-024-01714-3","DOIUrl":"10.1038/s41593-024-01714-3","url":null,"abstract":"Perineuronal nets (PNNs) are densely packed extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. PNNs stabilize synapses inhibiting synaptic plasticity. Here we show that synaptic terminals of fast-spiking interneurons localize to holes in the PNNs in the adult mouse somatosensory cortex. Approximately 95% of holes in the PNNs contain synapses and astrocytic processes expressing Kir4.1, glutamate and GABA transporters. Hence, holes in the PNNs contain tripartite synapses. In the adult mouse brain, PNN degradation causes an expanded astrocytic coverage of the neuronal somata without altering the axon terminals. The loss of PNNs impairs astrocytic transmitter and potassium uptake, resulting in the spillage of glutamate into the extrasynaptic space. Our data show that PNNs and astrocytes cooperate to contain synaptically released signals in physiological conditions. Their combined action is altered in mouse models of Alzheimer’s disease and epilepsy where PNNs are disrupted. Perineuronal nets stabilize synapses inhibiting synaptic plasticity. Here, the authors show that perineuronal nets act as a diffusion barrier facilitating astrocytic clearance of synaptically released ions and neurotransmitters.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01714-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141631376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A nonoscillatory, millisecond-scale embedding of brain state provides insight into behavior 非振荡、毫秒级的大脑状态嵌入可洞察行为
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-15 DOI: 10.1038/s41593-024-01715-2
David F. Parks, Aidan M. Schneider, Yifan Xu, Samuel J. Brunwasser, Samuel Funderburk, Danilo Thurber, Tim Blanche, Eva L. Dyer, David Haussler, Keith B. Hengen
{"title":"A nonoscillatory, millisecond-scale embedding of brain state provides insight into behavior","authors":"David F. Parks, Aidan M. Schneider, Yifan Xu, Samuel J. Brunwasser, Samuel Funderburk, Danilo Thurber, Tim Blanche, Eva L. Dyer, David Haussler, Keith B. Hengen","doi":"10.1038/s41593-024-01715-2","DOIUrl":"10.1038/s41593-024-01715-2","url":null,"abstract":"The most robust and reliable signatures of brain states are enriched in rhythms between 0.1 and 20 Hz. Here we address the possibility that the fundamental unit of brain state could be at the scale of milliseconds and micrometers. By analyzing high-resolution neural activity recorded in ten mouse brain regions over 24 h, we reveal that brain states are reliably identifiable (embedded) in fast, nonoscillatory activity. Sleep and wake states could be classified from 100 to 101 ms of neuronal activity sampled from 100 µm of brain tissue. In contrast to canonical rhythms, this embedding persists above 1,000 Hz. This high-frequency embedding is robust to substates, sharp-wave ripples and cortical on/off states. Individual regions intermittently switched states independently of the rest of the brain, and such brief state discontinuities coincided with brief behavioral discontinuities. Our results suggest that the fundamental unit of state in the brain is consistent with the spatial and temporal scale of neuronal computation. Parks, Schneider et al. show that brain states like sleep and wake can be reliably detected from milliseconds of neural activity in local regions in mice. Regions can briefly switch states independently, coinciding with fleeting behavioral changes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unlocking opioid neuropeptide dynamics with genetically encoded biosensors 利用基因编码生物传感器揭示阿片类神经肽的动态变化
IF 21.2 1区 医学
Nature neuroscience Pub Date : 2024-07-15 DOI: 10.1038/s41593-024-01697-1
Chunyang Dong, Raajaram Gowrishankar, Yihan Jin, Xinyi Jenny He, Achla Gupta, Huikun Wang, Nilüfer Sayar-Atasoy, Rodolfo J. Flores, Karan Mahe, Nikki Tjahjono, Ruqiang Liang, Aaron Marley, Grace Or Mizuno, Darren K. Lo, Qingtao Sun, Jennifer L. Whistler, Bo Li, Ivone Gomes, Mark Von Zastrow, Hugo A. Tejeda, Deniz Atasoy, Lakshmi A. Devi, Michael R. Bruchas, Matthew R. Banghart, Lin Tian
{"title":"Unlocking opioid neuropeptide dynamics with genetically encoded biosensors","authors":"Chunyang Dong, Raajaram Gowrishankar, Yihan Jin, Xinyi Jenny He, Achla Gupta, Huikun Wang, Nilüfer Sayar-Atasoy, Rodolfo J. Flores, Karan Mahe, Nikki Tjahjono, Ruqiang Liang, Aaron Marley, Grace Or Mizuno, Darren K. Lo, Qingtao Sun, Jennifer L. Whistler, Bo Li, Ivone Gomes, Mark Von Zastrow, Hugo A. Tejeda, Deniz Atasoy, Lakshmi A. Devi, Michael R. Bruchas, Matthew R. Banghart, Lin Tian","doi":"10.1038/s41593-024-01697-1","DOIUrl":"10.1038/s41593-024-01697-1","url":null,"abstract":"Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions. Dong et al. developed and validated κLight, δLight and µLight, a suite of genetically encoded opioid peptide sensors for probing opioid drugs and brain-region/circuit-specific opioid release in behaving animals.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01697-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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