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通过基因编码荧光传感器测量背外侧纹状体中的独特亚秒级多巴胺信号。

Distinct sub-second dopamine signaling in dorsolateral striatum measured by a genetically-encoded fluorescent sensor.

机构信息

Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.

Department of Bioengineering, George Mason University, Fairfax, VA, USA.

出版信息

Nat Commun. 2023 Sep 22;14(1):5915. doi: 10.1038/s41467-023-41581-3.

DOI:10.1038/s41467-023-41581-3
PMID:37739964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10517008/
Abstract

The development of genetically encoded dopamine sensors such as dLight has provided a new approach to measuring slow and fast dopamine dynamics both in brain slices and in vivo, possibly enabling dopamine measurements in areas like the dorsolateral striatum (DLS) where previously such recordings with fast-scan cyclic voltammetry (FSCV) were difficult. To test this, we first evaluated dLight photometry in mouse brain slices with simultaneous FSCV and found that both techniques yielded comparable results, but notable differences in responses to dopamine transporter inhibitors, including cocaine. We then used in vivo fiber photometry with dLight in mice to examine responses to cocaine in DLS. We also compared dopamine responses during Pavlovian conditioning across the striatum. We show that dopamine increases were readily detectable in DLS and describe transient dopamine kinetics, as well as slowly developing signals during conditioning. Overall, our findings indicate that dLight photometry is well suited to measuring dopamine dynamics in DLS.

摘要

像 dLight 这样的基因编码多巴胺传感器的发展为测量脑切片和体内的慢和快多巴胺动力学提供了一种新方法,这可能使得能够在以前使用快速扫描循环伏安法(FSCV)难以记录的区域,如背外侧纹状体(DLS),进行多巴胺测量。为了验证这一点,我们首先用同时的 FSCV 在小鼠脑切片中评估了 dLight 光光度法,发现这两种技术都产生了可比的结果,但对多巴胺转运体抑制剂的反应有明显差异,包括可卡因。然后,我们使用体内光纤光度法在小鼠中检查 DLS 中的可卡因反应。我们还比较了纹状体在巴甫洛夫条件反射过程中的多巴胺反应。我们表明,DLS 中很容易检测到多巴胺的增加,并描述了条件反射过程中多巴胺的瞬态动力学以及缓慢发展的信号。总的来说,我们的发现表明,dLight 光光度法非常适合测量 DLS 中的多巴胺动力学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/d422b4ddeb96/41467_2023_41581_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/0e4a990ce1e2/41467_2023_41581_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/1d2de3d4d414/41467_2023_41581_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/8db124c1838e/41467_2023_41581_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/d933807a6db2/41467_2023_41581_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/08de5f679a1a/41467_2023_41581_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/d422b4ddeb96/41467_2023_41581_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/0e4a990ce1e2/41467_2023_41581_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/1d2de3d4d414/41467_2023_41581_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/8db124c1838e/41467_2023_41581_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/d933807a6db2/41467_2023_41581_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/08de5f679a1a/41467_2023_41581_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/10517008/d422b4ddeb96/41467_2023_41581_Fig6_HTML.jpg

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