细胞分辨率和整体荧光记录钙活性产生体内药物功效的倒数读数。

IF 1.6 4区 医学 Q4 NEUROSCIENCES
Synapse Pub Date : 2025-03-01 DOI:10.1002/syn.70011
Seongsik Yun, Jones G Parker
{"title":"细胞分辨率和整体荧光记录钙活性产生体内药物功效的倒数读数。","authors":"Seongsik Yun, Jones G Parker","doi":"10.1002/syn.70011","DOIUrl":null,"url":null,"abstract":"<p><p>Genetically encoded fluorescent sensors of neural activity have become a mainstay of basic neuroscience. However, preclinical drug development has been slower to adopt these tools. Recently, we used miniature microscopes to record Ca<sup>2+</sup> activity in D1 and D2 dopamine receptor-expressing spiny projection neurons (SPNs) in response to antipsychotic drugs or candidates. Despite the fact that most antipsychotics block D2 receptors, clinical efficacy was associated with the normalization of D1-SPN activity under hyperdopaminergic conditions. In this study, we re-processed these data to approximate a fiber photometry signal and asked whether the conclusions were the same. This re-evaluation is important because fiber photometry has several advantages over cellular-resolution imaging. Consistent with our previous finding that bulk and cellular-resolution imaging report distinct SPN Ca<sup>2+</sup> dynamics, here the two data types suggested reciprocal effects of drug treatment on D1-SPN and D2-SPN Ca<sup>2+</sup> activity. While amphetamine treatment increased D1-SPN and decreased D2-SPN Ca<sup>2+</sup> event rates in cellular-resolution data, it increased the fluorescence of individual neurons but decreased their bulk fluorescence in both cell types. Analyzing detected bulk-fluorescence \"events\" yielded a closer correlation between the bulk and somatic Ca<sup>2+</sup> fluorescence. However, it did not fully replicate the results of our previous cellular-resolution recordings following amphetamine or antipsychotic drug treatment. Our results highlight important distinctions between cellular-resolution and bulk measurements of in vivo Ca<sup>2+</sup> activity. While experimenters using in vivo imaging to understand drug effects on neural activity should heed these distinctions, they should also utilize them to gain a more holistic view of drug action.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 2","pages":"e70011"},"PeriodicalIF":1.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866263/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cellular-Resolution and Bulk-Fluorescence Recordings of Calcium Activity Yield Reciprocal Readouts of In Vivo Drug Efficacy.\",\"authors\":\"Seongsik Yun, Jones G Parker\",\"doi\":\"10.1002/syn.70011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Genetically encoded fluorescent sensors of neural activity have become a mainstay of basic neuroscience. However, preclinical drug development has been slower to adopt these tools. Recently, we used miniature microscopes to record Ca<sup>2+</sup> activity in D1 and D2 dopamine receptor-expressing spiny projection neurons (SPNs) in response to antipsychotic drugs or candidates. Despite the fact that most antipsychotics block D2 receptors, clinical efficacy was associated with the normalization of D1-SPN activity under hyperdopaminergic conditions. In this study, we re-processed these data to approximate a fiber photometry signal and asked whether the conclusions were the same. This re-evaluation is important because fiber photometry has several advantages over cellular-resolution imaging. Consistent with our previous finding that bulk and cellular-resolution imaging report distinct SPN Ca<sup>2+</sup> dynamics, here the two data types suggested reciprocal effects of drug treatment on D1-SPN and D2-SPN Ca<sup>2+</sup> activity. While amphetamine treatment increased D1-SPN and decreased D2-SPN Ca<sup>2+</sup> event rates in cellular-resolution data, it increased the fluorescence of individual neurons but decreased their bulk fluorescence in both cell types. Analyzing detected bulk-fluorescence \\\"events\\\" yielded a closer correlation between the bulk and somatic Ca<sup>2+</sup> fluorescence. However, it did not fully replicate the results of our previous cellular-resolution recordings following amphetamine or antipsychotic drug treatment. Our results highlight important distinctions between cellular-resolution and bulk measurements of in vivo Ca<sup>2+</sup> activity. While experimenters using in vivo imaging to understand drug effects on neural activity should heed these distinctions, they should also utilize them to gain a more holistic view of drug action.</p>\",\"PeriodicalId\":22131,\"journal\":{\"name\":\"Synapse\",\"volume\":\"79 2\",\"pages\":\"e70011\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866263/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Synapse\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/syn.70011\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Synapse","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/syn.70011","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

神经活动的遗传编码荧光传感器已成为基础神经科学的支柱。然而,临床前药物开发采用这些工具的速度较慢。最近,我们使用微型显微镜记录了表达D1和D2多巴胺受体的棘投射神经元(SPNs)对抗精神病药物或候选药物的反应。尽管大多数抗精神病药物阻断D2受体,但临床疗效与高多巴胺能条件下D1-SPN活性的正常化有关。在这项研究中,我们重新处理这些数据以近似纤维光度测量信号,并询问结论是否相同。这种重新评估很重要,因为纤维光度法比细胞分辨率成像有几个优势。与我们之前的发现一致,大体积和细胞分辨率成像报告不同的SPN Ca2+动力学,这里的两种数据类型表明药物治疗对D1-SPN和D2-SPN Ca2+活性的相互作用。在细胞分辨率数据中,安非他明处理增加了D1-SPN并降低了D2-SPN Ca2+事件率,但在两种细胞类型中,它增加了单个神经元的荧光,但降低了它们的整体荧光。分析检测到的体积荧光“事件”产生了体积和体细胞Ca2+荧光之间更密切的相关性。然而,它并不能完全复制我们之前在安非他明或抗精神病药物治疗后的细胞分辨率记录的结果。我们的结果突出了细胞分辨率和体内Ca2+活性的大量测量之间的重要区别。当实验人员使用体内成像来了解药物对神经活动的影响时,他们应该注意到这些区别,他们也应该利用它们来获得药物作用的更全面的观点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cellular-Resolution and Bulk-Fluorescence Recordings of Calcium Activity Yield Reciprocal Readouts of In Vivo Drug Efficacy.

Genetically encoded fluorescent sensors of neural activity have become a mainstay of basic neuroscience. However, preclinical drug development has been slower to adopt these tools. Recently, we used miniature microscopes to record Ca2+ activity in D1 and D2 dopamine receptor-expressing spiny projection neurons (SPNs) in response to antipsychotic drugs or candidates. Despite the fact that most antipsychotics block D2 receptors, clinical efficacy was associated with the normalization of D1-SPN activity under hyperdopaminergic conditions. In this study, we re-processed these data to approximate a fiber photometry signal and asked whether the conclusions were the same. This re-evaluation is important because fiber photometry has several advantages over cellular-resolution imaging. Consistent with our previous finding that bulk and cellular-resolution imaging report distinct SPN Ca2+ dynamics, here the two data types suggested reciprocal effects of drug treatment on D1-SPN and D2-SPN Ca2+ activity. While amphetamine treatment increased D1-SPN and decreased D2-SPN Ca2+ event rates in cellular-resolution data, it increased the fluorescence of individual neurons but decreased their bulk fluorescence in both cell types. Analyzing detected bulk-fluorescence "events" yielded a closer correlation between the bulk and somatic Ca2+ fluorescence. However, it did not fully replicate the results of our previous cellular-resolution recordings following amphetamine or antipsychotic drug treatment. Our results highlight important distinctions between cellular-resolution and bulk measurements of in vivo Ca2+ activity. While experimenters using in vivo imaging to understand drug effects on neural activity should heed these distinctions, they should also utilize them to gain a more holistic view of drug action.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Synapse
Synapse 医学-神经科学
CiteScore
3.80
自引率
0.00%
发文量
38
审稿时长
4-8 weeks
期刊介绍: SYNAPSE publishes articles concerned with all aspects of synaptic structure and function. This includes neurotransmitters, neuropeptides, neuromodulators, receptors, gap junctions, metabolism, plasticity, circuitry, mathematical modeling, ion channels, patch recording, single unit recording, development, behavior, pathology, toxicology, etc.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信