High field BOLD response to forepaw stimulation in the mouse
High field BOLD response to forepaw stimulation in the mouse
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DOI：
10.1016/j.neuroimage.2010.02.083
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发表时间：
2010-06-01
期刊：
影响因子：
5.7
通讯作者：
Hoehn, Mathias
中科院分区：
文献类型：
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作者：
Adamczak, Joanna M.;Farr, Tracy D.;Hoehn, Mathias
我们已经建立了一个强大的协议，纵向功能磁共振成像在小鼠在高场MRI使用美托咪定麻醉。在麻醉动物中，电前爪刺激被广泛用于在初级躯体感觉皮层中产生BOLD对比。为了保持神经元的活动，大多数功能性磁共振成像实验使用α-氯醛糖产生镇静作用，但严重的副作用使这种方法不适合生存实验。作为有利的替代方案，α（2）-肾上腺素能受体激动剂美托咪定已成功应用于大鼠的纵向fMRI研究。随着转基因技术的出现，小鼠模型变得越来越有吸引力，从而提高了对小鼠实施合适的fMRI方案的需求。因此，我们研究了使用美托咪定在C57 BL/6小鼠中进行重复fMRI实验。我们评估了皮下应用的最佳美托咪定剂量。记录对侧体感皮层的体感诱发电位（SSEP），以评估前爪刺激后美托咪啶下的脑活动。重复给予美托咪定（纵向脑激活研究的要求）耐受性良好。使用前爪刺激范例，我们观察到BOLD对比度在对侧躯体感觉皮层中的相似的50%，使用梯度回波回波平面成像（GE-EPI）进行扫描。然而，在高场强下对小小鼠大脑进行成像是具有挑战性的，并且我们在皮层中的GE-EPI图像中观察到强烈的磁化率伪影。我们已经开发了一种琼脂凝胶帽，用于成功补偿这些伪影，作为成功进行11.7T小鼠fMRI的先决条件。建立的方案将适用于转基因动物的脑激活研究和小鼠脑损伤后功能缺陷和恢复的研究。(C)2010年爱思唯尔公司All rights reserved.
We have established a robust protocol for longitudinal fMRI in mice at high field MRI using a medetomidine anesthesia. Electrical forepaw stimulation in anesthetized animals is widely used to produce BOLD contrast in the primary somatosensory cortex. To preserve neuronal activity, most fMRI experiments used alpha-chloralose to produce sedation, but severe side effects make this procedure unsuitable for survival experiments. As advantageous alternative, the alpha(2)-adrenergic receptor agonist medetomidine has been applied successfully to permit longitudinal fMRI studies in rats. With the advent of transgenic technology, mouse models have become increasingly attractive raising the demand for implementation of a suitable fMRI protocol for mice. Therefore, we investigated the use of medetomidine for repetitive fMRI experiments in C57BL/6 mice. We evaluated the optimal medetomidine dose for subcutaneous application. Somatosensory evoked potentials (SSEPs) in the contralateral somatosensory cortex were recorded to assess brain activity under medetominidine following forepaw stimulation. Repetitive administration of medetomidine, the requirement for longitudinal brain activation studies, was well tolerated. Using the forepaw stimulation paradigm, we observed BOLD contrast in the contralateral somatosensory cortex in similar to 50% of the performed scans using gradient echo-echo planar imaging (GE-EPI). However, imaging the small mouse brain at high field strength is challenging and we observed strong susceptibility artifacts in GE-EPI images in the cortex. We have developed an agar gel cap for successful compensation of these artifacts as prerequisite for successful mouse fMRI at 11.7T. The established protocol will be suitable for brain activation studies in transgenic animals and for studies of functional deficit and recovery after brain injury in mice. (C) 2010 Elsevier Inc. All rights reserved.