Inferring neural circuit properties from optogenetic stimulation.
Inferring neural circuit properties from optogenetic stimulation.
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DOI：
10.1371/journal.pone.0205386
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Reynolds J
中科院分区：
文献类型：
--
作者：
Avery M;Nassi J;Reynolds J
光遗传学已经成为一个重要的工具，扰乱神经回路与无与伦比的时间精度和细胞类型的特异性。然而，直接激活特定的神经元亚群可以快速调节网络中其他神经元的活动，并可能导致意想不到的和复杂的下游效应。在这里，我们开发了一个生物约束的计算模型，利用这些非直观的网络响应，以深入了解网络的基本属性。我们将此模型应用于在警觉猕猴的初级视觉皮层中的光遗传学刺激期间记录的数据。在这些实验中，我们发现兴奋性神经元的光遗传学去极化通常抑制神经元反应，与正常化回路的参与一致。我们的模型表明，在这些反应中看到的抑制可能是由缓慢的兴奋性和抑制性传导通道介导的。此外，该模型预测，网络对光遗传学扰动的响应关键取决于网络的固有时间特性与视蛋白的时间特性之间的关系。与模型预测一致，与较慢的C1V1T视蛋白（tau = 60 ms）的刺激相比，C1V1TT视蛋白（具有快时间常数（tau = 45 ms）的视蛋白）的刺激在激光偏移后引起更快和更强的抑制作用。这项工作说明了如何利用光遗传学刺激产生的非直观网络反应来深入了解基础神经元计算的网络特性，例如归一化。因此，这种新型的混合光学理论方法可以增强光遗传学剖析复杂神经回路的能力。
Optogenetics has become an important tool for perturbing neural circuitry with unparalleled temporal precision and cell-type specificity. However, direct activation of a specific subpopulation of neurons can rapidly modulate the activity of other neurons within the network and may lead to unexpected and complex downstream effects. Here, we have developed a biologically-constrained computational model that exploits these non-intuitive network responses in order to gain insight into underlying properties of the network. We apply this model to data recorded during optogenetic stimulation in the primary visual cortex of the alert macaque. In these experiments, we found that optogenetic depolarization of excitatory neurons often suppressed neuronal responses, consistent with engagement of normalization circuitry. Our model suggests that the suppression seen in these responses may be mediated by slow excitatory and inhibitory conductance channels. Furthermore, the model predicted that the response of the network to optogenetic perturbation depends critically on the relationship between inherent temporal properties of the network and the temporal properties of the opsin. Consistent with model predictions, stimulation of the C1V1TT opsin, an opsin with a fast time constant (tau = 45 ms), caused faster and stronger suppressive effects after laser offset, as compared to stimulation of the slower C1V1T opsin (tau = 60ms). This work illustrates how the non-intuitive network responses that result from optogenetic stimulation can be exploited to gain insight regarding network properties that underlie fundamental neuronal computations, such as normalization. This novel hybrid opto-theoretical approach can thus enhance the power of optogenetics to dissect complex neural circuits.
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影响因子：
16.2
作者：
Nassi JJ;Avery MC;Cetin AH;Roe AW;Reynolds JH
通讯作者：
Reynolds JH
影响因子：
16.2
作者：
Herrero JL;Gieselmann MA;Sanayei M;Thiele A
通讯作者：
Thiele A
影响因子：
9.2
作者：
Mateo, Celine;Avermann, Michael;Petersen, Carl C. H.
通讯作者：
Petersen, Carl C. H.
DOI：
10.1073/pnas.1119527109
发表时间：
2012-07-03
影响因子：
11.1
作者：
Self, Matthew W.;Kooijmans, Roxana N.;Roelfsema, Pieter R.
通讯作者：
Roelfsema, Pieter R.
影响因子：
16.2
作者：
Reynolds, John H.;Heeger, David J.
通讯作者：
Heeger, David J.