Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates.
Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates.
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DOI：
10.1038/s41598-018-21486-8
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发表时间：
2018-02-20
影响因子：
4.6
通讯作者：
Palfi S
中科院分区：
文献类型：
--
作者：
Senova S;Poupon C;Dauguet J;Stewart HJ;Dugué GP;Jan C;Hosomi K;Ralph GS;Barnes L;Drouot X;Pouzat C;Mangin JF;Pain F;Doignon I;Aron-Badin R;Brouillet E;Boyden ES;Mitrophanous KA;Hantraye P;Palfi S
解剖非人灵长类动物（NHP）的神经回路对于通过电神经调节识别用于治疗药物抗性神经精神疾病的潜在神经调节解剖靶点至关重要。脑深部电刺激（DBS）的靶点和经颅磁刺激（TMS）的皮质靶点如何比较并相互补充是一个重要的问题。结合光遗传学和纤维束成像可能使大型脑皮质-皮质下神经通路的解剖功能表征成为可能。为了概念验证，该方法用于NHP大脑中以表征运动皮质-底丘脑通路（m_CSP），该通路可能参与帕金森病（PD）的DBS作用机制。将编码视蛋白ChR 2基因的Rabies-G-假型化和Rabies-G-VSVg-假型化EIAV慢病毒载体立体定向注射到丘脑底核（subthalamic nucleus，丘脑底核）中，并逆行转运到投射到丘脑底核的运动皮质层。然后使用组织学引导的高角分辨率MRI纤维束成像准确引导m_CSP起源的皮质光刺激来进行该通路的精确解剖映射。m_CSP轴突终末或m_CSP皮质起源的光激发以非等效方式改变光敏性突触后神经元放电率的峰电位分布。光遗传纤维束成像可能有助于设计神经精神疾病的NHP模型的临床前神经调节研究，为测试的假设选择最合适的目标。
Dissecting neural circuitry in non-human primates (NHP) is crucial to identify potential neuromodulation anatomical targets for the treatment of pharmacoresistant neuropsychiatric diseases by electrical neuromodulation. How targets of deep brain stimulation (DBS) and cortical targets of transcranial magnetic stimulation (TMS) compare and might complement one another is an important question. Combining optogenetics and tractography may enable anatomo-functional characterization of large brain cortico-subcortical neural pathways. For the proof-of-concept this approach was used in the NHP brain to characterize the motor cortico-subthalamic pathway (m_CSP) which might be involved in DBS action mechanism in Parkinson’s disease (PD). Rabies-G-pseudotyped and Rabies-G-VSVg-pseudotyped EIAV lentiviral vectors encoding the opsin ChR2 gene were stereotaxically injected into the subthalamic nucleus (STN) and were retrogradely transported to the layer of the motor cortex projecting to STN. A precise anatomical mapping of this pathway was then performed using histology-guided high angular resolution MRI tractography guiding accurately cortical photostimulation of m_CSP origins. Photoexcitation of m_CSP axon terminals or m_CSP cortical origins modified the spikes distribution for photosensitive STN neurons firing rate in non-equivalent ways. Optogenetic tractography might help design preclinical neuromodulation studies in NHP models of neuropsychiatric disease choosing the most appropriate target for the tested hypothesis.
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影响因子：
16.2
作者：
Drouot', X;Oshino, S;Palfi, S
通讯作者：
Palfi, S
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
DOI：
10.1073/pnas.1405003111
发表时间：
2014-10-14
影响因子：
11.1
作者：
Fox, Michael D.;Buckner, Randy L.;Pascual-Leone, Alvaro
通讯作者：
Pascual-Leone, Alvaro
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。
影响因子：
3.5
作者：
Takada M;Inoue K;Koketsu D;Kato S;Kobayashi K;Nambu A
通讯作者：
Nambu A