SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice
SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice
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DOI：
10.1016/j.neuroimage.2014.09.023
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发表时间：
2014-12-01
期刊：
影响因子：
5.7
通讯作者：
Goldschmidt, Juergen
中科院分区：
文献类型：
--
作者：
Kolodziej, Angela;Lippert, Michael;Goldschmidt, Juergen
电和光遗传学脑刺激方法广泛应用于啮齿类动物，用于操纵行为和分析神经元回路的功能连接。这些刺激引起的全脑激活模式的高分辨率活体成像仍然具有挑战性，特别是在清醒行为的小鼠中。在这里，我们使用一种新的单光子发射计算机断层扫描（SPECT）成像区域脑血流（rCBF）的方案，绘制了清醒的脑内自我刺激小鼠的脑激活模式。小鼠分别被植入用于电刺激内侧前脑束的电极（mfb-microstim）和用于蓝光刺激腹侧被盖区表达通道视紫红质-2神经元的光纤（vta-optostim）。在分别进行电流或光照自我刺激训练后，小鼠被植入颈静脉导管，并在7至10分钟的颅内自我刺激或无刺激的持续行为中静脉注射流量示踪剂99m -锝六甲基丙烯胺肟（99mTc-HMPAO）。采用多针孔SPECT对麻醉动物进行刺激后99mtc的脑区分布进行绘制。自我刺激后，微刺激小鼠电极尖端rCBF显著增加。在vta光刺激小鼠中，在刺激部位外发现了峰值激活。在两组中都发现了部分重叠的激活和失活的全脑网络。当对所有自我刺激小鼠与所有对照进行测试时，发现伏隔核顶部内侧壳高度显著激活。在正在进行的行为中使用静脉示踪剂注射的rCBF spect成像是一种新的工具，用于成像清醒行为的啮齿动物的区域大脑激活模式，提供比18f -2-氟-2-葡萄糖正电子发射断层扫描更高的空间和时间分辨率。(C) 2014年作者。Elsevier Inc.出版。这是一篇基于CC BY-NC-ND许可（http://creativecommons.org/licenses/by-nc-nd/3.0/）的开放获取文章。
Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99 m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18 F-2-fluoro-2-dexoyglucose positron emission tomography. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).