Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice.
Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice.
复制标题
DOI：
10.3389/fncir.2013.00162
复制
发表时间：
2013
影响因子：
3.5
通讯作者：
Isa T
中科院分区：
文献类型：
--
作者：
Sooksawate T;Isa K;Matsui R;Kato S;Kinoshita M;Kobayashi K;Watanabe D;Kobayashi K;Isa T
最近，通过使用两种病毒载体的组合，我们开发了一种用于通路选择性和可逆性突触传递阻断的技术，并成功地通过影响脊髓中间神经元群体来诱导猕猴灵巧手运动的行为缺陷。为了探索这种技术在其他途径和物种中的工作能力，并获得基本的方法学信息，我们试图阻断小鼠中的交叉顶盖网状通路，该通路已知控制对视觉目标的定向反应。将具有编码增强型破伤风神经毒素（eTeNT）的基因的神经元特异性逆行基因转移载体在四环素反应元件的控制下用增强型绿色荧光蛋白（EGFP）标记，注射到左侧内侧脑桥网状结构中。7-17几天后，将具有高效Tet-ON序列的腺相关病毒载体rtTAV 16注射到右侧上级丘中。5-9 6周后，开始每天给予多西环素（Dox）。Dox给药后1-4天，朝向左侧的视觉定向反应受损。抗GFP免疫组织化学染色显示，右侧上级中、深层有大量神经元染色阳性，表明eTeNT表达。在Dox施用终止后，抗GFP染色在28天内恢复到基线水平。从第一次Dox给药终止后28天开始的第二轮Dox给药导致行为障碍的再现。这些发现表明，突触传递的通路选择性和可逆性阻断也会导致啮齿动物的行为效应，并且交叉的顶盖-网状通路明显控制视觉定向行为。
Recently, by using a combination of two viral vectors, we developed a technique for pathway-selective and reversible synaptic transmission blockade, and successfully induced a behavioral deficit of dexterous hand movements in macaque monkeys by affecting a population of spinal interneurons. To explore the capacity of this technique to work in other pathways and species, and to obtain fundamental methodological information, we tried to block the crossed tecto-reticular pathway, which is known to control orienting responses to visual targets, in mice. A neuron-specific retrograde gene transfer vector with the gene encoding enhanced tetanus neurotoxin (eTeNT) tagged with enhanced green fluorescent protein (EGFP) under the control of a tetracycline responsive element was injected into the left medial pontine reticular formation. 7–17 days later, an adeno-associated viral vector with a highly efficient Tet-ON sequence, rtTAV16, was injected into the right superior colliculus. 5–9 weeks later, the daily administration of doxycycline (Dox) was initiated. Visual orienting responses toward the left side were impaired 1–4 days after Dox administration. Anti-GFP immunohistochemistry revealed that a number of neurons in the intermediate and deep layers of the right superior colliculus were positively stained, indicating eTeNT expression. After the termination of Dox administration, the anti-GFP staining returned to the baseline level within 28 days. A second round of Dox administration, starting from 28 days after the termination of the first Dox administration, resulted in the reappearance of the behavioral impairment. These findings showed that pathway-selective and reversible blockade of synaptic transmission also causes behavioral effects in rodents, and that the crossed tecto-reticular pathway clearly controls visual orienting behaviors.
登录
查看更多内容
影响因子：
12.4
作者：
Markakis, Eleni A.;Vives, Kenneth P.;Redmond, D. Eugene, Jr.
通讯作者：
Redmond, D. Eugene, Jr.
影响因子：
2.5
作者：
Quaia, C;Aizawa, H;Wurtz, RH
通讯作者：
Wurtz, RH
影响因子：
2.5
作者：
KAWAMURA, K;BRODAL, A
通讯作者：
BRODAL, A
影响因子：
2
作者：
GRANTYN, A;BERTHOZ, A
通讯作者：
BERTHOZ, A
影响因子：
4.2
作者：
Kato, Shigeki;Inoue, Ken-Ichi;Kobayashi, Kazuto
通讯作者：
Kobayashi, Kazuto