Pub Date : 2024-07-08DOI: 10.1038/s41593-024-01712-5
Noam Gannot, Xingyu Li, Chrystian D. Phillips, Ayse Bilge Ozel, Karin Harumi Uchima Koecklin, John P. Lloyd, Lusi Zhang, Katie Emery, Tomer Stern, Jun Z. Li, Peng Li
Coughing is a respiratory behavior that plays a crucial role in protecting the respiratory system. Here we show that the nucleus of the solitary tract (NTS) in mice contains heterogenous neuronal populations that differentially control breathing. Within these subtypes, activation of tachykinin 1 (Tac1)-expressing neurons triggers specific respiratory behaviors that, as revealed by our detailed characterization, are cough-like behaviors. Chemogenetic silencing or genetic ablation of Tac1 neurons inhibits cough-like behaviors induced by tussive challenges. These Tac1 neurons receive synaptic inputs from the bronchopulmonary chemosensory and mechanosensory neurons in the vagal ganglion and coordinate medullary regions to control distinct aspects of cough-like defensive behaviors. We propose that these Tac1 neurons in the NTS are a key component of the airway–vagal–brain neural circuit that controls cough-like defensive behaviors in mice and that they coordinate the downstream modular circuits to elicit the sequential motor pattern of forceful expiratory responses. Gannot et al. show that Tac1 neurons in the NTS mediate an airway–vagal–brain pathway that is crucial for coughing in mice. These neurons receive direct vagal sensory inputs and coordinate downstream circuits to control coughing.
{"title":"A vagal–brainstem interoceptive circuit for cough-like defensive behaviors in mice","authors":"Noam Gannot, Xingyu Li, Chrystian D. Phillips, Ayse Bilge Ozel, Karin Harumi Uchima Koecklin, John P. Lloyd, Lusi Zhang, Katie Emery, Tomer Stern, Jun Z. Li, Peng Li","doi":"10.1038/s41593-024-01712-5","DOIUrl":"10.1038/s41593-024-01712-5","url":null,"abstract":"Coughing is a respiratory behavior that plays a crucial role in protecting the respiratory system. Here we show that the nucleus of the solitary tract (NTS) in mice contains heterogenous neuronal populations that differentially control breathing. Within these subtypes, activation of tachykinin 1 (Tac1)-expressing neurons triggers specific respiratory behaviors that, as revealed by our detailed characterization, are cough-like behaviors. Chemogenetic silencing or genetic ablation of Tac1 neurons inhibits cough-like behaviors induced by tussive challenges. These Tac1 neurons receive synaptic inputs from the bronchopulmonary chemosensory and mechanosensory neurons in the vagal ganglion and coordinate medullary regions to control distinct aspects of cough-like defensive behaviors. We propose that these Tac1 neurons in the NTS are a key component of the airway–vagal–brain neural circuit that controls cough-like defensive behaviors in mice and that they coordinate the downstream modular circuits to elicit the sequential motor pattern of forceful expiratory responses. Gannot et al. show that Tac1 neurons in the NTS mediate an airway–vagal–brain pathway that is crucial for coughing in mice. These neurons receive direct vagal sensory inputs and coordinate downstream circuits to control coughing.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556739","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}
Pub Date : 2024-07-05DOI: 10.1038/s41593-024-01685-5
Yizhak Sofer, Noga Zilkha, Elena Gimpel, Shlomo Wagner, Silvia Gabriela Chuartzman, Tali Kimchi
In nature, both males and females engage in competitive aggressive interactions to resolve social conflicts, yet the behavioral principles guiding such interactions and their underlying neural mechanisms remain poorly understood. Through circuit manipulations in wild mice, we unveil oxytocin-expressing (OT+) neurons in the hypothalamic paraventricular nucleus (PVN) as a neural hub governing behavior in dyadic and intragroup social conflicts, influencing the degree of behavioral sexual dimorphism. We demonstrate that OT+ PVN neurons are essential and sufficient in promoting aggression and dominance hierarchies, predominantly in females. Furthermore, pharmacogenetic activation of these neurons induces a change in the ‘personality’ traits of the mice within groups, in a sex-dependent manner. Finally, we identify an innervation from these OT neurons to the ventral tegmental area that drives dyadic aggression, in a sex-specific manner. Our data suggest that competitive aggression in naturalistic settings is mediated by a sexually dimorphic OT network connected with reward-related circuitry. In nature, female mice, like males, display aggression and dominant hierarchy. This study in wild mice identifies oxytocin-expressing neurons as a hub governing these behaviors, influencing the degree of sexual dimorphism in social conflicts.
在自然界中，雄性和雌性都会通过竞争性的攻击性互动来解决社会冲突，但人们对指导这种互动的行为原理及其潜在的神经机制仍然知之甚少。通过对野生小鼠进行回路操作，我们揭示了下丘脑室旁核（PVN）中表达催产素（OT+）的神经元是支配二人和群体内社会冲突行为的神经枢纽，影响行为的性别二态性程度。我们证明，OT+ PVN 神经元在促进攻击性和支配等级方面是必不可少和足够的，主要是在雌性中。此外，这些神经元的药物基因激活会诱导小鼠在群体中的 "个性 "特征发生变化，这种变化与性别有关。最后，我们确定了这些OT神经元向腹侧被盖区的神经传导，这种传导以性别特异性的方式驱动着二人攻击行为。我们的数据表明，自然环境中的竞争性攻击行为是由与奖赏相关电路相连的性双态 OT 网络介导的。
{"title":"Sexually dimorphic oxytocin circuits drive intragroup social conflict and aggression in wild house mice","authors":"Yizhak Sofer, Noga Zilkha, Elena Gimpel, Shlomo Wagner, Silvia Gabriela Chuartzman, Tali Kimchi","doi":"10.1038/s41593-024-01685-5","DOIUrl":"10.1038/s41593-024-01685-5","url":null,"abstract":"In nature, both males and females engage in competitive aggressive interactions to resolve social conflicts, yet the behavioral principles guiding such interactions and their underlying neural mechanisms remain poorly understood. Through circuit manipulations in wild mice, we unveil oxytocin-expressing (OT+) neurons in the hypothalamic paraventricular nucleus (PVN) as a neural hub governing behavior in dyadic and intragroup social conflicts, influencing the degree of behavioral sexual dimorphism. We demonstrate that OT+ PVN neurons are essential and sufficient in promoting aggression and dominance hierarchies, predominantly in females. Furthermore, pharmacogenetic activation of these neurons induces a change in the ‘personality’ traits of the mice within groups, in a sex-dependent manner. Finally, we identify an innervation from these OT neurons to the ventral tegmental area that drives dyadic aggression, in a sex-specific manner. Our data suggest that competitive aggression in naturalistic settings is mediated by a sexually dimorphic OT network connected with reward-related circuitry. In nature, female mice, like males, display aggression and dominant hierarchy. This study in wild mice identifies oxytocin-expressing neurons as a hub governing these behaviors, influencing the degree of sexual dimorphism in social conflicts.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538286","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}
Pub Date : 2024-07-04DOI: 10.1038/s41593-024-01694-4
Patricia Bonnavion, Christophe Varin, Ghazal Fakhfouri, Pilar Martinez Olondo, Aurélie De Groote, Amandine Cornil, Ramiro Lorenzo Lopez, Elisa Pozuelo Fernandez, Elsa Isingrini, Quentin Rainer, Kathleen Xu, Eleni Tzavara, Erika Vigneault, Sylvie Dumas, Alban de Kerchove d’Exaerde, Bruno Giros
The role of the striatum in motor control is commonly assumed to be mediated by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing dopamine (DA) D1 receptors or D2 receptors (D1-SPNs and D2-SPNs, respectively), without regard to SPNs coexpressing both receptors (D1/D2-SPNs). Here we developed an approach to target these hybrid SPNs in mice and demonstrate that, although these SPNs are less abundant, they have a major role in guiding the motor function of the other two populations. D1/D2-SPNs project exclusively to the external globus pallidus and have specific electrophysiological features with distinctive integration of DA signals. Gain- and loss-of-function experiments indicate that D1/D2-SPNs potentiate the prokinetic and antikinetic functions of D1-SPNs and D2-SPNs, respectively, and restrain the integrated motor response to psychostimulants. Overall, our findings demonstrate the essential role of this population of D1/D2-coexpressing neurons in orchestrating the fine-tuning of DA regulation in thalamo-cortico-striatal loops. Bonnavion, Varin and colleagues show that striatal projection neurons that coexpress dopamine D1 and D2 receptors have unique physiological properties and serve as a crucial third output in the striatum for motor control and dopaminergic signal integration.
{"title":"Striatal projection neurons coexpressing dopamine D1 and D2 receptors modulate the motor function of D1- and D2-SPNs","authors":"Patricia Bonnavion, Christophe Varin, Ghazal Fakhfouri, Pilar Martinez Olondo, Aurélie De Groote, Amandine Cornil, Ramiro Lorenzo Lopez, Elisa Pozuelo Fernandez, Elsa Isingrini, Quentin Rainer, Kathleen Xu, Eleni Tzavara, Erika Vigneault, Sylvie Dumas, Alban de Kerchove d’Exaerde, Bruno Giros","doi":"10.1038/s41593-024-01694-4","DOIUrl":"10.1038/s41593-024-01694-4","url":null,"abstract":"The role of the striatum in motor control is commonly assumed to be mediated by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing dopamine (DA) D1 receptors or D2 receptors (D1-SPNs and D2-SPNs, respectively), without regard to SPNs coexpressing both receptors (D1/D2-SPNs). Here we developed an approach to target these hybrid SPNs in mice and demonstrate that, although these SPNs are less abundant, they have a major role in guiding the motor function of the other two populations. D1/D2-SPNs project exclusively to the external globus pallidus and have specific electrophysiological features with distinctive integration of DA signals. Gain- and loss-of-function experiments indicate that D1/D2-SPNs potentiate the prokinetic and antikinetic functions of D1-SPNs and D2-SPNs, respectively, and restrain the integrated motor response to psychostimulants. Overall, our findings demonstrate the essential role of this population of D1/D2-coexpressing neurons in orchestrating the fine-tuning of DA regulation in thalamo-cortico-striatal loops. Bonnavion, Varin and colleagues show that striatal projection neurons that coexpress dopamine D1 and D2 receptors have unique physiological properties and serve as a crucial third output in the striatum for motor control and dopaminergic signal integration.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521653","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}
Pub Date : 2024-07-03DOI: 10.1038/s41593-024-01699-z
Charltien Long, Kwang Lee, Long Yang, Theresia Dafalias, Alexander K. Wu, Sotiris C. Masmanidis
Dopaminergic neurons play a crucial role in associative learning, but their capacity to regulate behavior on subsecond timescales remains debated. It is thought that dopaminergic neurons drive certain behaviors by rapidly modulating striatal spiking activity; however, a view has emerged that only artificially high (that is, supra-physiological) dopamine signals alter behavior on fast timescales. This raises the possibility that moment-to-moment striatal spiking activity is not strongly shaped by dopamine signals in the physiological range. To test this, we transiently altered dopamine levels while monitoring spiking responses in the ventral striatum of behaving mice. These manipulations led to only weak changes in striatal activity, except when dopamine release exceeded reward-matched levels. These findings suggest that dopaminergic neurons normally play a minor role in the subsecond modulation of striatal dynamics in relation to other inputs and demonstrate the importance of discerning dopaminergic neuron contributions to brain function under physiological and potentially nonphysiological conditions.
{"title":"Constraints on the subsecond modulation of striatal dynamics by physiological dopamine signaling","authors":"Charltien Long, Kwang Lee, Long Yang, Theresia Dafalias, Alexander K. Wu, Sotiris C. Masmanidis","doi":"10.1038/s41593-024-01699-z","DOIUrl":"https://doi.org/10.1038/s41593-024-01699-z","url":null,"abstract":"<p>Dopaminergic neurons play a crucial role in associative learning, but their capacity to regulate behavior on subsecond timescales remains debated. It is thought that dopaminergic neurons drive certain behaviors by rapidly modulating striatal spiking activity; however, a view has emerged that only artificially high (that is, supra-physiological) dopamine signals alter behavior on fast timescales. This raises the possibility that moment-to-moment striatal spiking activity is not strongly shaped by dopamine signals in the physiological range. To test this, we transiently altered dopamine levels while monitoring spiking responses in the ventral striatum of behaving mice. These manipulations led to only weak changes in striatal activity, except when dopamine release exceeded reward-matched levels. These findings suggest that dopaminergic neurons normally play a minor role in the subsecond modulation of striatal dynamics in relation to other inputs and demonstrate the importance of discerning dopaminergic neuron contributions to brain function under physiological and potentially nonphysiological conditions.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141495870","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}
Pub Date : 2024-07-03DOI: 10.1038/s41593-024-01695-3
Damien Levard, Célia Seillier, Mathys Bellemain-Sagnard, Antoine Philippe Fournier, Eloïse Lemarchand, Chantal Dembech, Gaëtan Riou, Karina McDade, Colin Smith, Conor McQuaid, Axel Montagne, Lukas Amann, Marco Prinz, Denis Vivien, Marina Rubio
Age is a major nonmodifiable risk factor for ischemic stroke. Central nervous system-associated macrophages (CAMs) are resident immune cells located along the brain vasculature at the interface between the blood circulation and the parenchyma. By using a clinically relevant thromboembolic stroke model in young and aged male mice and corresponding human tissue samples, we show that during aging, CAMs acquire a central role in orchestrating immune cell trafficking after stroke through the specific modulation of adhesion molecules by endothelial cells. The absence of CAMs provokes increased leukocyte infiltration (neutrophils and CD4+ and CD8+ T lymphocytes) and neurological dysfunction after stroke exclusively in aged mice. Major histocompatibility complex class II, overexpressed by CAMs during aging, plays a significant role in the modulation of immune responses to stroke. We demonstrate that during aging, CAMs become central coordinators of the neuroimmune response that ensure a long-term fine-tuning of the immune responses triggered by stroke. How aging influences peripheral immune cell infiltration and the role of these cells following traumatic injury of the CNS is unclear. Here, the authors show that aging transforms CNS-associated macrophages into regulators of immune cell trafficking after ischemic stroke, modulating neurological outcomes.
年龄是缺血性中风的一个主要不可改变的危险因素。中枢神经系统相关巨噬细胞（CAMs）是沿脑血管分布的常驻免疫细胞，位于血液循环与脑实质的交界处。我们利用临床相关的血栓栓塞性中风模型在年轻和老年雄性小鼠及相应的人类组织样本中进行研究，结果表明，在衰老过程中，CAMs 通过内皮细胞对粘附分子的特异性调节，在中风后协调免疫细胞迁移方面发挥了核心作用。CAMs 的缺失会导致中风后白细胞浸润（中性粒细胞、CD4+ 和 CD8+ T 淋巴细胞）和神经功能障碍的增加，而这些现象只发生在老年小鼠身上。主要组织相容性复合体 II 类在衰老过程中由 CAMs 过度表达，在中风的免疫反应调节中起着重要作用。我们证明，在衰老过程中，CAMs 成为神经免疫反应的核心协调者，确保中风引发的免疫反应得到长期微调。
{"title":"Central nervous system-associated macrophages modulate the immune response following stroke in aged mice","authors":"Damien Levard, Célia Seillier, Mathys Bellemain-Sagnard, Antoine Philippe Fournier, Eloïse Lemarchand, Chantal Dembech, Gaëtan Riou, Karina McDade, Colin Smith, Conor McQuaid, Axel Montagne, Lukas Amann, Marco Prinz, Denis Vivien, Marina Rubio","doi":"10.1038/s41593-024-01695-3","DOIUrl":"10.1038/s41593-024-01695-3","url":null,"abstract":"Age is a major nonmodifiable risk factor for ischemic stroke. Central nervous system-associated macrophages (CAMs) are resident immune cells located along the brain vasculature at the interface between the blood circulation and the parenchyma. By using a clinically relevant thromboembolic stroke model in young and aged male mice and corresponding human tissue samples, we show that during aging, CAMs acquire a central role in orchestrating immune cell trafficking after stroke through the specific modulation of adhesion molecules by endothelial cells. The absence of CAMs provokes increased leukocyte infiltration (neutrophils and CD4+ and CD8+ T lymphocytes) and neurological dysfunction after stroke exclusively in aged mice. Major histocompatibility complex class II, overexpressed by CAMs during aging, plays a significant role in the modulation of immune responses to stroke. We demonstrate that during aging, CAMs become central coordinators of the neuroimmune response that ensure a long-term fine-tuning of the immune responses triggered by stroke. How aging influences peripheral immune cell infiltration and the role of these cells following traumatic injury of the CNS is unclear. Here, the authors show that aging transforms CNS-associated macrophages into regulators of immune cell trafficking after ischemic stroke, modulating neurological outcomes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141495879","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}
Pub Date : 2024-07-03DOI: 10.1038/s41593-024-01689-1
Rachel S. Lee, Yotam Sagiv, Ben Engelhard, Ilana B. Witten, Nathaniel D. Daw
The hypothesis that midbrain dopamine (DA) neurons broadcast a reward prediction error (RPE) is among the great successes of computational neuroscience. However, recent results contradict a core aspect of this theory: specifically that the neurons convey a scalar, homogeneous signal. While the predominant family of extensions to the RPE model replicates the classic model in multiple parallel circuits, we argue that these models are ill suited to explain reports of heterogeneity in task variable encoding across DA neurons. Instead, we introduce a complementary ‘feature-specific RPE’ model, positing that individual ventral tegmental area DA neurons report RPEs for different aspects of an animal’s moment-to-moment situation. Further, we show how our framework can be extended to explain patterns of heterogeneity in action responses reported among substantia nigra pars compacta DA neurons. This theory reconciles new observations of DA heterogeneity with classic ideas about RPE coding while also providing a new perspective of how the brain performs reinforcement learning in high-dimensional environments. The authors present a feature-specific prediction error model that explains heterogeneity in dopaminergic signals within and across projection-defined populations. Model-derived predictions of dopamine activity align with empirical recordings.
中脑多巴胺（DA）神经元播报奖赏预测错误（RPE）的假说是计算神经科学的伟大成就之一。然而，最近的研究结果却与这一理论的核心内容相矛盾：具体来说，神经元传递的是一种标量、同质的信号。虽然 RPE 模型的主要扩展系列在多个并行电路中复制了经典模型，但我们认为这些模型并不适合解释有关 DA 神经元任务变量编码异质性的报告。相反，我们引入了一个互补的 "特异性 RPE "模型，假设单个腹侧被盖区 DA 神经元针对动物瞬间情况的不同方面报告 RPE。此外，我们还展示了如何扩展我们的框架，以解释黑质紧密区 DA 神经元报告的动作反应的异质性模式。这一理论调和了对 DA 异质性的新观察和有关 RPE 编码的经典观点，同时也为大脑如何在高维环境中进行强化学习提供了一个新的视角。
{"title":"A feature-specific prediction error model explains dopaminergic heterogeneity","authors":"Rachel S. Lee, Yotam Sagiv, Ben Engelhard, Ilana B. Witten, Nathaniel D. Daw","doi":"10.1038/s41593-024-01689-1","DOIUrl":"10.1038/s41593-024-01689-1","url":null,"abstract":"The hypothesis that midbrain dopamine (DA) neurons broadcast a reward prediction error (RPE) is among the great successes of computational neuroscience. However, recent results contradict a core aspect of this theory: specifically that the neurons convey a scalar, homogeneous signal. While the predominant family of extensions to the RPE model replicates the classic model in multiple parallel circuits, we argue that these models are ill suited to explain reports of heterogeneity in task variable encoding across DA neurons. Instead, we introduce a complementary ‘feature-specific RPE’ model, positing that individual ventral tegmental area DA neurons report RPEs for different aspects of an animal’s moment-to-moment situation. Further, we show how our framework can be extended to explain patterns of heterogeneity in action responses reported among substantia nigra pars compacta DA neurons. This theory reconciles new observations of DA heterogeneity with classic ideas about RPE coding while also providing a new perspective of how the brain performs reinforcement learning in high-dimensional environments. The authors present a feature-specific prediction error model that explains heterogeneity in dopaminergic signals within and across projection-defined populations. Model-derived predictions of dopamine activity align with empirical recordings.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141495896","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}
Pub Date : 2024-07-02DOI: 10.1038/s41593-024-01690-8
Madeleine C. Snyder, Kevin K. Qi, Michael M. Yartsev
Here we conducted wireless electrophysiological recording of hippocampal neurons from Egyptian fruit bats in the presence of human experimenters. In flying bats, many neurons modulated their activity depending on the identity of the human at the landing target. In stationary bats, many neurons carried significant spatial information about the position and identity of humans traversing the environment. Our results reveal that hippocampal activity is robustly modulated by the presence, movement and identity of human experimenters. Snyder et al. report that hippocampal neurons in Egyptian fruit bats modulate their activity depending on the position and identity of human experimenters when bats are flying and encode experimenter position and identity when bats are stationary.
{"title":"Neural representation of human experimenters in the bat hippocampus","authors":"Madeleine C. Snyder, Kevin K. Qi, Michael M. Yartsev","doi":"10.1038/s41593-024-01690-8","DOIUrl":"10.1038/s41593-024-01690-8","url":null,"abstract":"Here we conducted wireless electrophysiological recording of hippocampal neurons from Egyptian fruit bats in the presence of human experimenters. In flying bats, many neurons modulated their activity depending on the identity of the human at the landing target. In stationary bats, many neurons carried significant spatial information about the position and identity of humans traversing the environment. Our results reveal that hippocampal activity is robustly modulated by the presence, movement and identity of human experimenters. Snyder et al. report that hippocampal neurons in Egyptian fruit bats modulate their activity depending on the position and identity of human experimenters when bats are flying and encode experimenter position and identity when bats are stationary.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01690-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489632","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}
Pub Date : 2024-07-02DOI: 10.1038/s41593-024-01677-5
Allwyn Pereira, Jeisimhan Diwakar, Giacomo Masserdotti, Sude Beşkardeş, Tatiana Simon, Younju So, Lucía Martín-Loarte, Franziska Bergemann, Lakshmy Vasan, Tamas Schauer, Anna Danese, Riccardo Bocchi, Maria Colomé-Tatché, Carol Schuurmans, Anna Philpott, Tobias Straub, Boyan Bonev, Magdalena Götz
Direct neuronal reprogramming is a promising approach to regenerate neurons from local glial cells. However, mechanisms of epigenome remodeling and co-factors facilitating this process are unclear. In this study, we combined single-cell multiomics with genome-wide profiling of three-dimensional nuclear architecture and DNA methylation in mouse astrocyte-to-neuron reprogramming mediated by Neurogenin2 (Ngn2) and its phosphorylation-resistant form (PmutNgn2), respectively. We show that Ngn2 drives multilayered chromatin remodeling at dynamic enhancer–gene interaction sites. PmutNgn2 leads to higher reprogramming efficiency and enhances epigenetic remodeling associated with neuronal maturation. However, the differences in binding sites or downstream gene activation cannot fully explain this effect. Instead, we identified Yy1, a transcriptional co-factor recruited by direct interaction with Ngn2 to its target sites. Upon deletion of Yy1, activation of neuronal enhancers, genes and ultimately reprogramming are impaired without affecting Ngn2 binding. Thus, our work highlights the key role of interactors of proneural factors in direct neuronal reprogramming. The molecular mechanisms underlying direct neuronal reprogramming are unclear. Here the authors show Ngn2-mediated chromatin remodeling and its binding sites underlying mouse astrocyte-to-neuron reprogramming and identify Yy1, a transcription co-factor, as an important regulator.
{"title":"Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1","authors":"Allwyn Pereira, Jeisimhan Diwakar, Giacomo Masserdotti, Sude Beşkardeş, Tatiana Simon, Younju So, Lucía Martín-Loarte, Franziska Bergemann, Lakshmy Vasan, Tamas Schauer, Anna Danese, Riccardo Bocchi, Maria Colomé-Tatché, Carol Schuurmans, Anna Philpott, Tobias Straub, Boyan Bonev, Magdalena Götz","doi":"10.1038/s41593-024-01677-5","DOIUrl":"10.1038/s41593-024-01677-5","url":null,"abstract":"Direct neuronal reprogramming is a promising approach to regenerate neurons from local glial cells. However, mechanisms of epigenome remodeling and co-factors facilitating this process are unclear. In this study, we combined single-cell multiomics with genome-wide profiling of three-dimensional nuclear architecture and DNA methylation in mouse astrocyte-to-neuron reprogramming mediated by Neurogenin2 (Ngn2) and its phosphorylation-resistant form (PmutNgn2), respectively. We show that Ngn2 drives multilayered chromatin remodeling at dynamic enhancer–gene interaction sites. PmutNgn2 leads to higher reprogramming efficiency and enhances epigenetic remodeling associated with neuronal maturation. However, the differences in binding sites or downstream gene activation cannot fully explain this effect. Instead, we identified Yy1, a transcriptional co-factor recruited by direct interaction with Ngn2 to its target sites. Upon deletion of Yy1, activation of neuronal enhancers, genes and ultimately reprogramming are impaired without affecting Ngn2 binding. Thus, our work highlights the key role of interactors of proneural factors in direct neuronal reprogramming. The molecular mechanisms underlying direct neuronal reprogramming are unclear. Here the authors show Ngn2-mediated chromatin remodeling and its binding sites underlying mouse astrocyte-to-neuron reprogramming and identify Yy1, a transcription co-factor, as an important regulator.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-024-01677-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489645","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}
Pub Date : 2024-07-02DOI: 10.1038/s41593-024-01691-7
Neurons in the hippocampus of Egyptian fruit bats modulate their activity during a spatial reward task depending on the identity of the human experimenter at the goal location. A separate subpopulation of neurons carries significant spatial information about the positions and identities of humans traversing the same environment while bats are stationary.
{"title":"Hippocampal neurons encode identities and positions of human experimenters","authors":"","doi":"10.1038/s41593-024-01691-7","DOIUrl":"10.1038/s41593-024-01691-7","url":null,"abstract":"Neurons in the hippocampus of Egyptian fruit bats modulate their activity during a spatial reward task depending on the identity of the human experimenter at the goal location. A separate subpopulation of neurons carries significant spatial information about the positions and identities of humans traversing the same environment while bats are stationary.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492782","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}
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