Developmental Neurobiology最新文献_第7页

Polycomb-mediated gene regulation in human brain development and neurodevelopmental disorders polycomb介导的基因调控在人脑发育和神经发育障碍中的作用

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-04-05 DOI: 10.1002/dneu.22876

Nora Bölicke, Mareike Albert

{"title":"Polycomb-mediated gene regulation in human brain development and neurodevelopmental disorders","authors":"Nora Bölicke, Mareike Albert","doi":"10.1002/dneu.22876","DOIUrl":"10.1002/dneu.22876","url":null,"abstract":"The neocortex is considered the seat of higher cognitive function in humans. It develops from a sheet of neural progenitor cells, most of which eventually give rise to neurons. This process of cell fate determination is controlled by precise temporal and spatial gene expression patterns that in turn are affected by epigenetic mechanisms including Polycomb group (PcG) regulation. PcG proteins assemble in multiprotein complexes and catalyze repressive posttranslational histone modifications. Their association with neurodevelopmental disease and various types of cancer of the central nervous system, as well as observations in mouse models, has implicated these epigenetic modifiers in controlling various stages of cortex development. The precise mechanisms conveying PcG‐associated transcriptional repression remain incompletely understood and are an active field of research. PcG activity appears to be highly context‐specific, raising the question of species‐specific differences in the regulation of neural stem and progenitor regulation. In this review, we will discuss our growing understanding of how PcG regulation affects human cortex development, based on studies in murine model systems, but focusing mostly on findings obtained from examining impaired PcG activity in the context of human neurodevelopmental disorders and cancer. Furthermore, we will highlight relevant experimental approaches for functional investigations of PcG regulation in human cortex development.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 4","pages":"345-363"},"PeriodicalIF":3.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48595924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 9

Cortical myelination in toddlers and preschoolers with autism spectrum disorder 患有自闭症谱系障碍的幼儿和学龄前儿童的皮层髓鞘形成

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-03-29 DOI: 10.1002/dneu.22874

Bosi Chen, Annika Linke, Lindsay Olson, Jiwandeep Kohli, Mikaela Kinnear, Martin Sereno, Ralph-Axel Müller, Ruth Carper, Inna Fishman

{"title":"Cortical myelination in toddlers and preschoolers with autism spectrum disorder","authors":"Bosi Chen, Annika Linke, Lindsay Olson, Jiwandeep Kohli, Mikaela Kinnear, Martin Sereno, Ralph-Axel Müller, Ruth Carper, Inna Fishman","doi":"10.1002/dneu.22874","DOIUrl":"10.1002/dneu.22874","url":null,"abstract":"Intracortical myelin is thought to play a significant role in the development of neural circuits and functional networks, with consistent evidence of atypical network connectivity in children with autism spectrum disorder (ASD). However, little is known about the development of intracortical myelin in the first years of life in ASD, during the critical neurodevelopmental period when autism symptoms first emerge. Using T1-weighted (T1w) and T2w structural magnetic resonance imaging (MRI) in 21 young children with ASD and 16 typically developing (TD) children, ages 1.5–5.5 years, we demonstrate the feasibility of estimating intracortical myelin in vivo using the T1w/T2w ratio as a proxy. The resultant T1w/T2w maps were largely comparable with those reported in prior T1w/T2w studies in TD children and adults, and revealed no group differences between TD children and those with ASD. However, differential associations between T1w/T2w and age were identified in several early myelinated regions (e.g., visual, posterior cingulate, precuneus cortices) in the ASD and TD groups, with age-related increase in estimated myelin content across the toddler and preschool years detected in TD children, but not in children with ASD. The atypical age-related effects in intracortical myelin, suggesting a disrupted myelination in the first years of life in ASD, may be related to the aberrant brain network connectivity reported in young children with ASD in some of the same cortical regions and circuits.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 3","pages":"261-274"},"PeriodicalIF":3.0,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41621953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 7

Cortical surface variation in individuals with excessive smartphone use 过度使用智能手机个体的皮质表面变化

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-03-25 DOI: 10.1002/dneu.22872

Dusan Hirjak, Gudrun M. Henemann, Mike M. Schmitgen, Larissa Götz, Nadine D. Wolf, Katharina M. Kubera, Fabio Sambataro, Tagrid Leménager, Julian Koenig, Robert Christian Wolf

{"title":"Cortical surface variation in individuals with excessive smartphone use","authors":"Dusan Hirjak, Gudrun M. Henemann, Mike M. Schmitgen, Larissa Götz, Nadine D. Wolf, Katharina M. Kubera, Fabio Sambataro, Tagrid Leménager, Julian Koenig, Robert Christian Wolf","doi":"10.1002/dneu.22872","DOIUrl":"10.1002/dneu.22872","url":null,"abstract":"Excessive smartphone use has been repeatedly related to adverse effects on mental health and psychological well-being in young adults. The continued investigation of the neurobiological mechanism underlying excessive smartphone use—sometimes also referred to as “smartphone addiction”(SPA)—is considered a top priority in system neuroscience research. Despite progress in the past years, cortical morphology associated with SPA is still poorly understood. Here, we used structural magnetic resonance imaging (MRI) at 3 T to investigate two cortical surface markers of distinct neurodevelopmental origin such as the complexity of cortical folding (CCF) and cortical thickness (CTh) in individuals with excessive smartphone use (n = 19) compared to individuals not fulfilling SPA criteria (n-SPA; n = 22). SPA was assessed using the Smartphone Addiction Inventory (SPAI). CCF and CTh were investigated using the Computational Anatomy Toolbox (CAT12). SPA individuals showed lower CCF in the right superior frontal gyrus as well as in the right caudal (cACC) and rostral anterior cingulate cortex (rACC) compared to n-SPA individuals (TFCE, uncorrected at p < 0.001). Following a dimensional approach, across the entire sample, CCF of the right cACC was significantly associated with SPAI total score, as well as with distinct SPAI subdimensions, particularly time spent with the device, compulsivity, and sleep interference in all participants (n = 41; p < 0.05, FDR-corrected). Collectively, these findings suggest that SPA is associated with aberrant structural maturation of regions important for cognitive control and emotional regulation.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 4","pages":"277-287"},"PeriodicalIF":3.0,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40326945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

Re-evaluating the actin-dependence of spectraplakin functions during axon growth and maintenance 重新评估轴突生长和维持过程中谱板功能的动作依赖性

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-03-25 DOI: 10.1002/dneu.22873

Yue Qu, Juliana Alves-Silva, Kriti Gupta, Ines Hahn, Jill Parkin, Natalia Sánchez-Soriano, Andreas Prokop

{"title":"Re-evaluating the actin-dependence of spectraplakin functions during axon growth and maintenance","authors":"Yue Qu, Juliana Alves-Silva, Kriti Gupta, Ines Hahn, Jill Parkin, Natalia Sánchez-Soriano, Andreas Prokop","doi":"10.1002/dneu.22873","DOIUrl":"10.1002/dneu.22873","url":null,"abstract":"Axons are the long and slender processes of neurons constituting the biological cables that wire the nervous system. The growth and maintenance of axons require loose microtubule bundles that extend through their entire length. Understanding microtubule regulation is therefore an essential aspect of axon biology. Key regulators of neuronal microtubules are the spectraplakins, a well-conserved family of cytoskeletal cross-linkers that underlie neuropathies in mouse and humans. Spectraplakin deficiency in mouse or Drosophila causes severe decay of microtubule bundles and reduced axon growth. The underlying mechanisms are best understood for Drosophila’s spectraplakin Short stop (Shot) and believed to involve cytoskeletal cross-linkage: Shot's binding to microtubules and Eb1 via its C-terminus has been thoroughly investigated, whereas its F-actin interaction via N-terminal calponin homology (CH) domains is little understood. Here, we have gained new understanding by showing that the F-actin interaction must be finely balanced: altering the properties of F-actin networks or deleting/exchanging Shot's CH domains induces changes in Shot function—with a Lifeact-containing Shot variant causing remarkable remodeling of neuronal microtubules. In addition to actin-microtubule (MT) cross-linkage, we find strong indications that Shot executes redundant MT bundle-promoting roles that are F-actin-independent. We argue that these likely involve the neuronal Shot-PH isoform, which is characterized by a large, unexplored central plakin repeat region (PRR) similarly existing also in mammalian spectraplakins.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 4","pages":"288-307"},"PeriodicalIF":3.0,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9195440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2

Developmental neural activity requires neuron–astrocyte interactions 发育中的神经活动需要神经元与星形胶质细胞的相互作用

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-02-28 DOI: 10.1002/dneu.22870

Bryce T. Bajar, Nguyen T. Phi, Harpreet Randhawa, Orkun Akin

引用次数: 0

Coactivator-associated arginine methyltransferase 1 controls oligodendrocyte differentiation in the corpus callosum during early brain development 协同激活子相关精氨酸甲基转移酶1控制早期大脑发育过程中胼胝体少突胶质细胞的分化

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-02-26 DOI: 10.1002/dneu.22871

Yugo Ishino, Shoko Shimizu, Masaya Tohyama, Shingo Miyata

{"title":"Coactivator-associated arginine methyltransferase 1 controls oligodendrocyte differentiation in the corpus callosum during early brain development","authors":"Yugo Ishino, Shoko Shimizu, Masaya Tohyama, Shingo Miyata","doi":"10.1002/dneu.22871","DOIUrl":"10.1002/dneu.22871","url":null,"abstract":"Protein arginine methylation has been recognized as one of key posttranslational modifications for refined protein functions, mediated by protein arginine methyltransferases (Prmts). Coactivator-associated arginine methyltransferase (Carm1, also known as Prmt4) participates in various cellular events, such as cell survival, proliferation, and differentiation through its protein arginine methylation activities. Carm1 regulates cell proliferation of a neuronal cell line and is reportedly expressed in the mammalian brain. However, its detailed function in the central nervous system, particularly in glial cells, remains largely unexplored. In this study, Carm1 exhibited relatively high expression in oligodendrocyte (OL) lineage cells present in the corpus callosum of the developing brain, followed by a remarkable downregulation after active myelination. The suppression of Carm1 activity by inhibitors in isolated oligodendrocyte precursor cells (OPCs) reduced the number of Ki67-expressing and BrdU-incorporated proliferating cells. Furthermore, Carm1 inactivation attenuated OL differentiation, as determined by the expression of Plp, a reliable myelin-related marker. It also impaired the extension of OL processes, accompanied by a significant reduction in gene expression related to OL differentiation and myelination, such as Sox10, Cnp, Myrf, and Mbp. In addition, OLs co-cultured with embryonic dorsal root ganglia neurons demonstrated that Carm1 activity is required for the appropriate formation of myelin processes and myelin sheaths around neuronal axons, and the induction of the clustering of Caspr, a node of Ranvier structural molecule. Thus, we propose that Carm1 is an essential molecule for the development of OPCs and OLs during brain development.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 3","pages":"245-260"},"PeriodicalIF":3.0,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45921870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 4

Maternal deprivation and milk replacement affect the integrity of gray and white matter in the developing lamb brain 母亲剥夺和母乳替代对发育中羔羊大脑灰质和白质完整性的影响

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-02-26 DOI: 10.1002/dneu.22869

Scott A. Love, Emmanuelle Haslin, Manon Bellardie, Frédéric Andersson, Laurent Barantin, Isabelle Filipiak, Hans Adriaensen, Csilla L. Fazekas, Laurène Leroy, Dóra Zelena, Mélody Morisse, Frédéric Elleboudt, Christian Moussu, Frédéric Lévy, Raymond Nowak, Elodie Chaillou

{"title":"Maternal deprivation and milk replacement affect the integrity of gray and white matter in the developing lamb brain","authors":"Scott A. Love, Emmanuelle Haslin, Manon Bellardie, Frédéric Andersson, Laurent Barantin, Isabelle Filipiak, Hans Adriaensen, Csilla L. Fazekas, Laurène Leroy, Dóra Zelena, Mélody Morisse, Frédéric Elleboudt, Christian Moussu, Frédéric Lévy, Raymond Nowak, Elodie Chaillou","doi":"10.1002/dneu.22869","DOIUrl":"10.1002/dneu.22869","url":null,"abstract":"The psychoendocrine evaluation of lamb development has demonstrated that maternal deprivation and milk replacement alters health, behavior, and endocrine profiles. While lambs are able to discriminate familiar and non-familiar conspecifics (mother or lamb), only lambs reared with their mother develop such clear social discrimination or preference. Lambs reared without mother display no preference for a specific lamb from its own group. Differences in exploratory and emotional behaviors between mother-reared and mother-deprived lambs have also been reported. As these behavioural abilities are supported by the brain, we hypothesize that rearing with maternal deprivation and milk replacement leads to altered brain development and maturation. To test this hypothesis, we examined brain morphometric and microstructural variables extracted from in vivo T1-weighted and diffusion-weighted magnetic resonance images acquired longitudinally (1 week, 1.5 months, and 4.5 months of age) in mother-reared and mother-deprived lambs. From the morphometric variables the caudate nuclei volume was found to be smaller for mother-deprived than for mother-reared lambs. T1-weighted signal intensity and radial diffusivity were higher for mother-deprived than for mother-reared lambs in both the white and gray matters. The fractional anisotropy of the white matter was lower for mother-deprived than for mother-reared lambs. Based on these morphometric and microstructural characteristics we conclude that maternal deprivation delays and affects lamb brain growth and maturation.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 2","pages":"214-232"},"PeriodicalIF":3.0,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42555879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Celsr family genes are dynamically expressed in embryonic and juvenile zebrafish Celsr家族基因在胚胎和幼年斑马鱼中动态表达

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-02-25 DOI: 10.1002/dneu.22868

Bhagyashri Joshi, Himanshu Gaur, Subhra Prakash Hui, Chinmoy Patra

{"title":"Celsr family genes are dynamically expressed in embryonic and juvenile zebrafish","authors":"Bhagyashri Joshi, Himanshu Gaur, Subhra Prakash Hui, Chinmoy Patra","doi":"10.1002/dneu.22868","DOIUrl":"10.1002/dneu.22868","url":null,"abstract":"The Cadherin EGF LAG seven-pass G-type receptor (Celsr) family belongs to the adhesion G-protein coupled receptor superfamily. In most vertebrates, the Celsr family has three members (CELSR1–3), whereas zebrafish display four paralogues (celsr1a, 1b, 2, 3). Although studies have shown the importance of the Celsr family in planar cell polarity, axonal guidance, and dendritic growth, the molecular mechanisms of the Celsr family regulating these cellular processes in vertebrates remain elusive. Zebrafish is an experimentally more amenable model to study vertebrate development, as zebrafish embryos develop externally, optically transparent, remain alive with malformed organs, and zebrafish is genetically similar to humans. Understanding the detailed expression pattern is the first step of exploring the functional mechanisms of the genes involved in development. Thus, we report the spatiotemporal expression pattern of Celsr family members in zebrafish nervous tissues. Our analysis shows that celsr1b and celsr2 are expressed maternally. In embryos, celsr1a, celsr1b, and celsr2 are expressed in the neural progenitors, and celsr3 is expressed in all five primary neural clusters of the brain and mantle layer of the spinal cord. In juvenile zebrafish, celsr1a, celsr1b, and celsr2 are presumably expressed in the neural progenitor enriched regions of the CNS. Therefore, the expression pattern of zebrafish Celsr family members is reminiscent of patterns described in other vertebrates or mammalian speciate. This indicates the conserved role of Celsr family genes in nervous system development and suggests zebrafish as an excellent model to explore the cellular and molecular mechanisms of Celsr family genes in vertebrate neurogenesis.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 2","pages":"192-213"},"PeriodicalIF":3.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2

Oligodendrocytes and myelin: Active players in neurodegenerative brains? 少突胶质细胞和髓磷脂:神经退行性脑的活跃参与者?

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-01-26 DOI: 10.1002/dneu.22867

Jing-Fei Chen, Fei Wang, Nan-Xing Huang, Lan Xiao, Feng Mei

{"title":"Oligodendrocytes and myelin: Active players in neurodegenerative brains?","authors":"Jing-Fei Chen, Fei Wang, Nan-Xing Huang, Lan Xiao, Feng Mei","doi":"10.1002/dneu.22867","DOIUrl":"10.1002/dneu.22867","url":null,"abstract":"Oligodendrocytes (OLs) are a major type of glial cells in the central nervous system that generate multiple myelin sheaths to wrap axons. Myelin ensures fast and efficient propagation of action potentials along axons and supports neurons with nourishment. The decay of OLs and myelin has been implicated in age-related neurodegenerative diseases and these changes are generally considered as an inevitable result of neuron loss and axon degeneration. Noticeably, OLs and myelin undergo dynamic changes in healthy adult brains, that is, newly formed OLs are continuously added throughout life from the differentiation of oligodendrocyte precursor cells (OPCs) and the pre-existing myelin sheaths may undergo degeneration or remodeling. Increasing evidence has shown that changes in OLs and myelin are present in the early stages of neurodegenerative diseases, and even prior to significant neuronal loss and functional deficits. More importantly, oligodendroglia-specific manipulation, by either deletion of the disease gene or enhancement of myelin renewal, can alleviate functional impairments in neurodegenerative animal models. These findings underscore the possibility that OLs and myelin are not passively but actively involved in neurodegenerative diseases and may play an important role in modulating neuronal function and survival. In this review, we summarize recent work characterizing by OLs and myelin changes in both healthy and neurodegenerative brains and discuss the potential of targeting oligodendroglial cells in treating neurodegenerative diseases.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 2","pages":"160-174"},"PeriodicalIF":3.0,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39738011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 12

Influence of developmental nicotine exposure on serotonergic control of breathing-related motor output 发育期尼古丁暴露对呼吸相关运动输出的血清素能控制的影响

IF 3 4区医学

Developmental Neurobiology Pub Date : 2022-01-11 DOI: 10.1002/dneu.22866

Lila Wollman, Andrew Hill, Brady Hasse, Christina Young, Giovanni Hernandez-De La Pena, Richard B Levine, Ralph F. Fregosi

{"title":"Influence of developmental nicotine exposure on serotonergic control of breathing-related motor output","authors":"Lila Wollman, Andrew Hill, Brady Hasse, Christina Young, Giovanni Hernandez-De La Pena, Richard B Levine, Ralph F. Fregosi","doi":"10.1002/dneu.22866","DOIUrl":"10.1002/dneu.22866","url":null,"abstract":"Serotonin plays an important role in the development of brainstem circuits that control breathing. Here, we test the hypothesis that developmental nicotine exposure (DNE) alters the breathing-related motor response to serotonin (5HT). Pregnant rats were exposed to nicotine or saline, and brainstem–spinal cord preparations from 1- to 5-day-old pups were studied in a split-bath configuration, allowing drugs to be applied selectively to the medulla or spinal cord. The activity of the fourth cervical ventral nerve roots (C4VR), which contain axons of phrenic motoneurons, was recorded. We applied 5HT alone or together with antagonists of 5HT1A, 5HT2A, or 5HT7 receptor subtypes. In control preparations, 5HT applied to the medulla consistently reduced C4VR frequency and this reduction could not be blocked by any of the three antagonists. In DNE preparations, medullary 5HT caused a large and sustained frequency increase (10 min), followed by a sustained decrease. Notably, the transient increase in frequency could be blocked by the independent addition of any of the antagonists. Experiments with subtype-specific agonists suggest that the 5HT7 subtype may contribute to the increased frequency response in the DNE preparations. Changes in C4VR burst amplitude in response to brainstem 5HT were uninfluenced by DNE. Addition of 5HT to the caudal chamber modestly increased phasic and greatly increased tonic C4VR activity, but there were no effects of DNE. The data show that DNE alters serotonergic signaling within brainstem circuits that control respiratory frequency but does not functionally alter serotonin signaling in the phrenic motoneuron pool.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"82 2","pages":"175-191"},"PeriodicalIF":3.0,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10799280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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