皮层神经元内在特性对神经信号编码稳态的调控作用

【作者】 陈娜；

【导师】 吴英良； 王晋辉；

【作者基本信息】 沈阳药科大学 ， 药理学， 2006， 博士

【摘要】 大脑高级中枢通过编码神经信号语言来控制人的运动、情感、意识和认知等行为。神经信号编码调控行为活动与神经元本身内在特性、突触传递特性和整个神经网络特性有关。要破解神经信号和行为的对应关系，就先要了解神经信号语言。神经信号语言主要涵盖以下信息：神经信号的编码模式即发放形式（适应性群集动作电位和紧张型群集动作电位），动作电位的编码频率（或称为信息容量）和动作电位的发放稳定性（即信息的忠实性）。无论是动作电位的发放模式、发放频率和发放稳定性都受到突触动力学和神经元编码动作电位的内在特性（阈电位水平、不应期和后超极化等）的限制和调控。所以定量描述神经元动作电位的内在特性和突触动力学特性对于我们解释神经信号的行为控制是至关重要的。我们运用电生理（如全细胞膜片钳和细胞贴覆式单通道技术）和药理学方法研究了感觉运动皮层锥体神经元、中间神经元和小脑浦肯野细胞的内在特性，即阈电位水平、不应期和后超极化，对神经元群集发放动作电位的发放容量和发放精确性的影响及基于Na⁺通道的可能机制。结果表明：三种神经元的阈电位水平、不应期和后超极化等这些内在特性不尽相同，但是都与群集动作电位的发放容量和发放位相精确性成线性相关性。外来兴奋性输入和抑制性后超极化可以调控神经元动作电位的编码特性，并且是通过神经元本身编码动作电位的内在特性起作用。此外，细胞内Ca²⁺信号与神经细胞兴奋性、编码精确性和自身稳态调控有关。通过对电压门控Na⁺通道的单通道记录，我们发现电压门控Na⁺通道的通道特性与全细胞模式下动作电位发放内在特性吻合。提示，神经元编码动作电位的内在特性是直接受电压门控Na⁺通道调控的。此外，兴奋性输入强度和超极化可以影响电压门控Na⁺通道的激活和再活化，表明突触输入可塑性可以诱导电压门控Na⁺通道的可塑性，从而引起神经元编码动作电位内在特性的可塑性。并且电压门控Na⁺通道介导的内在特性（阈电压和不应期）对中枢神经元群集动作电位的编码调控作用并不依赖于K⁺通道的作用。我们的实验结果为阐明神经元信号精确分析计算的细胞分子机制提供了一定的理论依据。更多还原

【Abstract】 The brain programs neural codes, including the patterns of synaptic transmission, the digital patterns of neuronal spikes and their non-synchronous outputs in neural network, precisely and loyally to guide well-organized behaviors, such as the motion, perception and cognition. In terms of neural codes at each of neurons, the patterns of sequential spikes （tonic and adaptive） as well as the timing precision and capacity of spikes are believed to be the critical parameters. Less is clear about how sodium channel-mediated intrinsic mechanisms set the spike programming, though synaptic inputs and potassium channels affect neuronal excitability. It is needed to elucidate such intrinsic mechanisms underlying the programming of sequential spikesWith electrophysiological and pharmacological approaches, we investigated the role of refractory periods for generating subsequent spikes and threshold potentials for evoking spikes in programming sequential spikes at cortical regular-spiking and fast-spiking neurons as well as cerebellar Purkinje cells. We also studied the kinetics of voltage-gated sodium channels, which is relevant to these intrinsic properties.Our results show that the patterns of sequential spikes at these three kinds of neurons in response to the given inputs from excitatory and inhibitory synapses are different, and that their spike patterns undergo plastic change with input intensities. To address the intrinsic mechanisms underlying such spike programming, we develop the methods to measure the refractory periods and threshold potentials of sequential spikes. We found that the values of spike capacity and timing precision at these neurons are associated with neuronal intrinsic properties, i.e., the shorter refractory periods and lower threshold potentials are associated with the higher spike capacity and the more precise spike timing, or vice versa. The capacity and timing precision of sequential spikes are linearly correlated with their refractory periods and threshold potentials. The enhanced excitatory inputs cause an increase in the spike capacity and timing precision through shortening refractory periods; and the inhibitory inputs immediately after each of spikes improve spike capacity and timing precision through lowering threshold potentials and refractory periods. Intracellular Ca²⁺ regulates the neuronal intrinsic properties, and in turn changes spike programming. With recording the activities of single voltage-gated sodium channels （VGSC）, we found that VGSC- mediated intrinsic properties mechanistically navigate spike programming.Our data indicate that the programming of sequential spikes at central neurons is essentially controlled by VGSC-mediated intrinsic mechanisms, which are the central mechanisms for the change of spike patterns driven by synaptic inputs. Our studies provides fundamental approaches and clues for decoding the precise and loyal neural signals that guide the well-organized behaviors.更多还原