Bidirectional modulation of deep cerebellar nuclear cells revealed by optogenetic manipulation of inhibitory inputs from Purkinje cells.
Bidirectional modulation of deep cerebellar nuclear cells revealed by optogenetic manipulation of inhibitory inputs from Purkinje cells.
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DOI：
10.1016/j.neuroscience.2014.07.006
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发表时间：
2014-09-26
期刊：
影响因子：
3.3
通讯作者：
Turner EE
中科院分区：
文献类型：
--
作者：
Han VZ;Magnus G;Zhang Y;Wei AD;Turner EE
在哺乳动物小脑中，小脑深部核（DCN）细胞将皮层浦肯野细胞（PCs）的所有信息传递到运动前核和其他脑区。然而，DCN细胞如何整合来自pc的抑制性输入和来自其他来源的兴奋性输入一直很难评估，部分原因是皮质pc和它们在细胞核中的靶细胞之间存在很大的空间间隔。为了避免这个问题，我们使用了cre介导的遗传方法来产生小鼠，其中通道视紫红质-2 （ChR2）与荧光报告基因融合，在gaba能神经元（包括pc）中选择性表达。在该模型的脑切片制备记录中，哺乳动物的pc可以通过短暂的光刺激进行稳健的去极化和放电。在突触后DCN细胞的记录中，PC轴突的光刺激引起强烈的抑制，类似于这些细胞对局灶电刺激的反应，但不需要在此类实验中通常应用的谷氨酸受体阻滞剂。在这个光遗传学模型中，短至1毫秒的激光脉冲可以可靠地诱导抑制，使DCN细胞的自发尖峰关闭约50毫秒。如果发射这种短暂的光脉冲，就会出现固定的双稳态爆发模式。如果这些脉冲连续地传递到自发双稳态细胞，对这种光刺激的直接反应是在细胞去极化状态下的抑制性反应和在膜重极化状态下的兴奋性反应；刺激终止后，一种不太规律的爆发模式持续存在。这些结果表明，DCN细胞的尖峰活动可以通过皮质pc的光激活突触抑制双向调节。
In the mammalian cerebellum, deep cerebellar nuclear (DCN) cells convey all information from cortical Purkinje cells (PCs) to premotor nuclei and other brain regions. However, how DCN cells integrate inhibitory input from PCs with excitatory inputs from other sources has been difficult to assess, in part due to the large spatial separation between cortical PCs and their target cells in the nuclei. To circumvent this problem we have used a Cre-mediated genetic approach to generate mice in which channelrhodopsin-2 (ChR2), fused with a fluorescent reporter, is selectively expressed by GABAergic neurons, including PCs. In recordings from brain slice preparations from this model, mammalian PCs can be robustly depolarized and discharged by brief photo stimulation. In recordings of postsynaptic DCN cells, photo stimulation of PC axons induces a strong inhibition that resembles these cells' responses to focal electrical stimulation, but without a requirement for the glutamate receptor blockers typically applied in such experiments. In this optogenetic model, laser pulses as brief as 1 ms can reliably induce an inhibition that shuts down the spontaneous spiking of a DCN cell for ∼50 ms. If bursts of such brief light pulses are delivered, a fixed pattern of bistable bursting emerges. If these pulses are delivered continuously to a spontaneously bistable cell, the immediate response to such photostimulation is inhibitory in the cell's depolarized state and excitatory when the membrane has repolarized; a less regular burst pattern then persists after stimulation has been terminated. These results indicate that the spiking activity of DCN cells can be bidirectionally modulated by the optically activated synaptic inhibition of cortical PCs.
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影响因子：
25
作者：
Alvina, Karina;Walter, Joy T.;Kohn, Adam;Ellis-Davies, Graham;Khodakhah, Kamran
通讯作者：
Khodakhah, Kamran
影响因子：
2.5
作者：
Aizenman, CD;Linden, DJ
通讯作者：
Linden, DJ
DOI：
10.1073/pnas.1302310110
发表时间：
2013-10-01
影响因子：
11.1
作者：
Chaumont, Joseph;Guyon, Nicolas;Isope, Philippe
通讯作者：
Isope, Philippe
影响因子：
5.3
作者：
Baumel, Yuval;Jacobson, Gilad A;Cohen, Dana
通讯作者：
Cohen, Dana
影响因子：
16.2
作者：
Aizenman, CD;Manis, PB;Linden, DJ
通讯作者：
Linden, DJ