Elucidating information processing in primate basal ganglia circuitry: a novel technique for pathway-selective ablation mediated by immunotoxin.
Elucidating information processing in primate basal ganglia circuitry: a novel technique for pathway-selective ablation mediated by immunotoxin.
复制标题
在灵长类动物基底神经节电路中阐明信息处理：一种由免疫毒素介导的途径选择性消融的新技术。
DOI：
10.3389/fncir.2013.00140
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发表时间：
2013
影响因子：
3.5
通讯作者：
Nambu A
中科院分区：
文献类型：
--
作者：
Takada M;Inoue K;Koketsu D;Kato S;Kobayashi K;Nambu A
利用神经元特异性逆行基因转移载体（NeuRet载体），我们最近开发了一种新技术，可以在灵长类动物大脑中实现通路选择性消融。该技术由免疫毒素（IT）介导，消除构成特定通路的神经元群，而使其他通路完好无损。通过这种技术，我们尝试选择性地从基底神经节回路中去除超直接通路。超直接通路直接将运动皮层与丘脑底核（STN）连接起来，在运动控制中发挥着至关重要的作用。运动皮层受到电刺激后，内部苍白球节段 (GPi) 通常会引发由早期兴奋、抑制和晚期兴奋组成的三相反应。一些药物生理学证据表明早期兴奋可能源自超直接途径。在我们的实验中，将表达人白细胞介素2受体α亚基的NeuRet载体注射到猕猴的STN中。然后，对辅助运动区 (SMA) 进行 IT 注射。当记录 GPi 中单个神经元响应 SMA 刺激的活动时，发现早期兴奋显着减少，而抑制和晚期兴奋均不受影响。 GPi 神经元的自发放电率和模式仍有待改变。这清楚地表明 IT 介导的束靶向成功地消除了超直接通路，而 STN 神经元的自发活动不受影响。电生理学结果通过逆行和顺行神经元标记在组织学上得到证实。总体数据表明，运动皮层驱动的 GPi 神经元早期兴奋是通过超直接通路传递的。 IT介导的通路选择性消融技术将为阐明各种神经网络中的信息处理提供强大的工具。
Employing a neuron-specific retrograde gene-transfer vector (NeuRet vector), we have recently developed a novel technique that achieves pathway-selective ablation in the primate brain. This technique is mediated by immunotoxin (IT) and eliminates a neuronal population that constitutes a particular pathway, leaving other pathways intact. By means of this technique, we have made an attempt to remove the hyperdirect pathway selectively from basal ganglia circuitry. The hyperdirect pathway links the motor cortex to the subthalamic nucleus (STN) directly and plays a crucial role in motor control. After electrical stimulation in the motor cortex, triphasic responses consisting of an early excitation, an inhibition, and a late excitation are usually elicited in the internal pallidal segment (GPi). Several pieces of pharmacophysiological evidence imply that the early excitation may be derived from the hyperdirect pathway. In our experiments, the NeuRet vector expressing human interleukin-2 receptor α-subunit was injected into the STN of macaque monkeys. Then, IT injections were performed into the supplementary motor area (SMA). When single neuron activity in the GPi was recorded in response to the SMA stimulation, it was found that the early excitation was significantly reduced with neither the inhibition nor the late excitation affected. The spontaneous firing rate and pattern of GPi neurons remained to be altered. This clearly indicates that IT-mediated tract targeting successfully eliminated the hyperdirect pathway with spontaneous activity of STN neurons unaffected. The electrophysiological findings were histologically confirmed by retrograde and anterograde neuronal labeling. The overall data define that the motor cortically driven early excitation in GPi neurons is conveyed through the hyperdirect pathway. The IT-mediated pathway-selective ablation technique will provide a powerful tool for elucidating information processing in various neural networks.
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影响因子：
2.5
作者：
Nambu, A;Tokuno, H;Hasegawa, N
通讯作者：
Hasegawa, N
影响因子：
5.3
作者：
Isoda, Masaki;Hikosaka, Okihide
通讯作者：
Hikosaka, Okihide
影响因子：
2.5
作者：
HAMADA, I;DELONG, MR
通讯作者：
DELONG, MR
影响因子：
4.2
作者：
Kato, Shigeki;Inoue, Ken-Ichi;Kobayashi, Kazuto
通讯作者：
Kobayashi, Kazuto
影响因子：
5.7
作者：
Mink, J W;Thach, W T
通讯作者：
Thach, W T