Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition.
Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition.
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DOI：
10.1371/journal.pcbi.1006292
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发表时间：
2018-07
影响因子：
4.3
通讯作者：
Terman D
中科院分区：
文献类型：
--
作者：
Goldwyn JH;Slabe BR;Travers JB;Terman D
神经元处理和传递信息的方式是将大量的突触输入转化为尖峰活动。突触抑制通常抑制神经元的输出激发活动，并且通常被分类为对神经元的输出激发活动具有消减或分裂效应。减法抑制可以通过消除对非偏好输入的反应来缩小引起尖峰活动的输入范围。分裂性抑制是增益控制的一种形式：它在保持引起放电活动的输入范围的同时，改变放电频率。由于这两种抑制“模式”对神经编码有不同的影响，因此了解区分这些反应特征的生物物理机制是很重要的。在本研究中，我们使用神经元模型的模拟和数学分析来寻找抑制性输入具有减法或分裂效应的特定条件（参数集）。值得注意的是，我们发现了A型钾电流（IA）的新作用。在我们的模型中，这种快速激活、缓慢失活的外向电流充当了消减抑制和分裂抑制之间的开关。特别是，如果IA是强的（大的最大电导）和快速（激活的时间尺度类似于尖峰启动），那么抑制有一个减法神经放电的影响。相反，如果IA是弱或不够快激活，那么抑制有分裂的影响神经放电。我们解释这些发现，使用动力系统的方法（平面分析和快慢解剖）来定义如何尖峰阈值条件依赖于突触输入和IA。我们的研究结果表明，神经元可以通过突触可塑性和/或A型钾通道的电导和动力学的调制的组合来“自我调节”抑制的增益控制效应。IA的这种新作用将增加神经元和网络的灵活性，并可能与最近观察到的孤束核神经元的分裂抑制作用有关。神经元通过响应两种类型的突触输入而产生尖峰来处理信息。兴奋性输入增加尖峰频率，抑制性输入降低尖峰频率（通常）。然而，这两种输入类型之间的相互作用以及这些输入到尖峰输出的转换并不是简单的加法和减法。抑制性输入可以通过多种方式抑制输出。例如，在某些情况下，抑制调节尖峰活动的速率，同时保留引起尖峰活动的输入范围;一个重要的计算原理被称为增益控制。我们使用神经元模型的模拟和数学分析来识别神经元的属性，这些属性决定了抑制性输入如何影响尖峰活动。具体来说，我们演示了如何增益控制的抑制效果取决于A型钾电流。A型钾电流的这种新作用为神经元提供了一种灵活调节它们如何处理突触输入并将信号传输到大脑其他区域的方法。
Neurons process and convey information by transforming barrages of synaptic inputs into spiking activity. Synaptic inhibition typically suppresses the output firing activity of a neuron, and is commonly classified as having a subtractive or divisive effect on a neuron’s output firing activity. Subtractive inhibition can narrow the range of inputs that evoke spiking activity by eliminating responses to non-preferred inputs. Divisive inhibition is a form of gain control: it modifies firing rates while preserving the range of inputs that evoke firing activity. Since these two “modes” of inhibition have distinct impacts on neural coding, it is important to understand the biophysical mechanisms that distinguish these response profiles. In this study, we use simulations and mathematical analysis of a neuron model to find the specific conditions (parameter sets) for which inhibitory inputs have subtractive or divisive effects. Significantly, we identify a novel role for the A-type Potassium current (IA). In our model, this fast-activating, slowly-inactivating outward current acts as a switch between subtractive and divisive inhibition. In particular, if IA is strong (large maximal conductance) and fast (activates on a time-scale similar to spike initiation), then inhibition has a subtractive effect on neural firing. In contrast, if IA is weak or insufficiently fast-activating, then inhibition has a divisive effect on neural firing. We explain these findings using dynamical systems methods (plane analysis and fast-slow dissection) to define how a spike threshold condition depends on synaptic inputs and IA. Our findings suggest that neurons can “self-regulate” the gain control effects of inhibition via combinations of synaptic plasticity and/or modulation of the conductance and kinetics of A-type Potassium channels. This novel role for IA would add flexibility to neurons and networks, and may relate to recent observations of divisive inhibitory effects on neurons in the nucleus of the solitary tract. Neurons process information by generating spikes in response to two types of synaptic inputs. Excitatory inputs increase spike rates and inhibitory inputs decrease spike rates (typically). The interaction between these two input types and the transformation of these inputs into spike outputs is not, however, a simple matter of addition and subtraction. Inhibitory inputs can suppress outputs in a variety of ways. For instance, in some cases, inhibition adjusts the rate of spiking activity while preserving the range of inputs that evoke spiking activity; an important computational principle known as gain control. We use simulations and mathematical analysis of a neuron model to identify properties of a neuron that determine how inhibitory inputs affect spiking activity. Specifically, we demonstrate how the gain control effects of inhibition depend on the A-type Potassium current. This novel role for the A-type Potassium current provides a way for neurons to flexibly regulate how they process synaptic inputs and transmit signals to other areas of the brain.
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