Fernandez Fernando R, Malerba Paola, White John A
Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America.
PLoS Comput Biol. 2015 Apr 24;11(4):e1004188. doi: 10.1371/journal.pcbi.1004188. eCollection 2015 Apr.
The presence of voltage fluctuations arising from synaptic activity is a critical component in models of gain control, neuronal output gating, and spike rate coding. The degree to which individual neuronal input-output functions are modulated by voltage fluctuations, however, is not well established across different cortical areas. Additionally, the extent and mechanisms of input-output modulation through fluctuations have been explored largely in simplified models of spike generation, and with limited consideration for the role of non-linear and voltage-dependent membrane properties. To address these issues, we studied fluctuation-based modulation of input-output responses in medial entorhinal cortical (MEC) stellate cells of rats, which express strong sub-threshold non-linear membrane properties. Using in vitro recordings, dynamic clamp and modeling, we show that the modulation of input-output responses by random voltage fluctuations in stellate cells is significantly limited. In stellate cells, a voltage-dependent increase in membrane resistance at sub-threshold voltages mediated by Na+ conductance activation limits the ability of fluctuations to elicit spikes. Similarly, in exponential leaky integrate-and-fire models using a shallow voltage-dependence for the exponential term that matches stellate cell membrane properties, a low degree of fluctuation-based modulation of input-output responses can be attained. These results demonstrate that fluctuation-based modulation of input-output responses is not a universal feature of neurons and can be significantly limited by subthreshold voltage-gated conductances.
由突触活动引起的电压波动的存在是增益控制、神经元输出门控和放电率编码模型中的一个关键组成部分。然而，在不同的皮质区域，个体神经元输入-输出功能受电压波动调制的程度尚未明确。此外，通过波动进行的输入-输出调制的程度和机制在很大程度上是在简化的放电生成模型中进行探索的，并且对非线性和电压依赖性膜特性的作用考虑有限。为了解决这些问题，我们研究了大鼠内侧内嗅皮质（MEC）星状细胞中基于波动的输入-输出反应调制，这些细胞表现出强大的阈下非线性膜特性。通过体外记录、动态钳制和建模，我们表明星状细胞中随机电压波动对输入-输出反应的调制受到显著限制。在星状细胞中，由Na+电导激活介导的阈下电压下膜电阻的电压依赖性增加限制了波动引发放电的能力。同样，在指数项具有与星状细胞膜特性相匹配的浅电压依赖性的指数型漏电整合-放电模型中，基于波动的输入-输出反应调制程度较低。这些结果表明，基于波动的输入-输出反应调制并非神经元的普遍特征，并且可能受到阈下电压门控电导的显著限制。
