Neuronal gain modulability is determined by dendritic morphology: a computational optogenetic study
Neuronal gain modulability is determined by dendritic morphology: a computational optogenetic study
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神经元增益可调节性由树突形态决定：计算光遗传学研究
DOI：
10.1101/096586
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Jarvis S
中科院分区：
文献类型：
--
作者：
Jarvis S
神经元输入-输出功能的增益可能被调节的机制一直是许多研究的主题。然而，对树突在神经元增益控制中的作用知之甚少。基于光刺激的空间分布或模式的新的光发生实验范式为阐明单细胞功能的许多方面提供了前景，包括树突在增益控制中的作用。因此，我们开发了一个模型来研究树突状茎内竞争的兴奋性和抑制性输入如何改变神经元增益，将视蛋白的动力学模型纳入我们的模型中，以确保它是可实验测试的。为了研究神经元树的不同拓扑结构对神经元的输入输出特性的影响，我们生成了分支几何，这种分支几何复制了大多数常见神经元的形态特征，但保持了树突的分支数量和总面积近似不变。我们发现了神经元的增益可调整性与其树突形态之间的关系，具有中等分枝程度的两极树突的神经元最容易控制其输入-输出关系的增益。这一理论随后在两个现实神经元的例子上进行了测试和证实：1)V层锥体细胞-确认它们在神经回路中的作用，除了充当初级兴奋神经元外，还作为回路中的增益调节器，以及2)星状细胞。除了提供可测试的预测和双视蛋白的新应用外，我们的模型还表明，所有树突亚域的神经支配是完全增益调制所必需的，揭示了树突靶向在神经元增益控制产生中的重要性及其所伴随的功能。最后，我们的研究还表明，使用直流电注入胞体并绕过树突的神经生理学检查可能会遗漏一些重要的神经元功能，如增益调节。
The mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron’s input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron’s gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells—confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain modulation.