Descending projections from the substantia nigra pars reticulata differentially control seizures
Descending projections from the substantia nigra pars reticulata differentially control seizures
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DOI：
10.1073/pnas.1908176117
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发表时间：
2019-12-26
影响因子：
11.1
通讯作者：
Forcelli, Patrick A.
中科院分区：
文献类型：
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作者：
Wicker, Evan;Beck, Veronica C.;Forcelli, Patrick A.
三十年的研究表明，抑制黑质网状部（SNpr）可以减轻癫痫发作，但介导这种作用的回路仍然不清楚。 SNpr 投射到上丘 (DLSC) 和桥脚核 (PPN) 的深层和中间层，但这些投射的贡献尚不清楚。为了解决这一差距，我们通过光遗传学沉默了 SNpr 内的细胞体、DLSC 内的黑质顶盖末端和 PPN 内的黑质顶盖末端。抑制 SNpr 中的细胞体可抑制戊四唑 (PTZ) 诱发的全身性癫痫发作、前脑诱发的部分性癫痫发作、γ-丁内酯 (GBL) 诱发的失神性癫痫发作以及遗传性癫痫易感大鼠的听源性癫痫发作。引人注目的是，这些效应通过抑制黑质顶盖投射得到了充分再现。相比之下，沉默黑被盖末梢仅减少失神癫痫发作和 PTZ 诱发的癫痫发作加剧。这些数据强调了该回路的广谱抗惊厥功效，并证明特定的传出投射通路有差异地控制不同的癫痫类型。
Three decades of studies have shown that inhibition of the substantia nigra pars reticulata (SNpr) attenuates seizures, yet the circuits mediating this effect remain obscure. SNpr projects to the deep and intermediate layers of the superior colliculus (DLSC) and the pedunculopontine nucleus (PPN), but the contributions of these projections are unknown. To address this gap, we optogenetically silenced cell bodies within SNpr, nigrotectal terminals within DLSC, and nigrotegmental terminals within PPN. Inhibition of cell bodies in SNpr suppressed generalized seizures evoked by pentylenetetrazole (PTZ), partial seizures evoked from the fore-brain, absence seizures evoked by gamma-butyrolactone (GBL), and audiogenic seizures in genetically epilepsy-prone rats. Strikingly, these effects were fully recapitulated by silencing nigrotectal projections. By contrast, silencing nigrotegmental terminals reduced only absence seizures and exacerbated seizures evoked by PTZ. These data underscore the broad-spectrum anticonvulsant efficacy of this circuit, and demonstrate that specific efferent projection pathways differentially control different seizure types.