神经元的稳定性与随机性整数倍放电

在大鼠损伤背根节神经元的自发放电中发现了整数倍放电,为了阐明这种放电所产生的原因,首先研究神经元模型中确定性混沌所引起的整数倍放电与噪声所诱发的整数放电的峰峰间期序列,通过分析得到前者的ＩＳＩ序列是非线性可预报的,具有确定的非线性特性,但由噪声所诱发的整数倍放电的ＩＳＩ序列是不可预报的,这表明这两种机制所产生的整数倍放电具有不同的特点,存在着定笥的差别,并且混沌运动所产生的整数倍放电是由混沌中各种     

大鼠视上核神经元自发放电节律的确定性机制

利用非线性动力学的方法,在多种生物数据中找到了确定性机制。大鼠下丘脑视上核（ｓｕｐｒａｏｐｔｉｃ ｎｕｃｌｅｕｓ,ＳＯＮ）神经元自发产生不规则的放电。为了研究这些不规则放电是否含有确定性机制,用电流钳对大鼠ＳＯＮ神经元进行全细胞纪录,取动作电位峰峰间期序列（ｉｎｔｅｒｓｐｉｋｅ ｉｎｔｅｒｖａｌ,ＩＳＩ）作为研究对象。采用一种新的检测时间序列非稳定周期轨道的方法分析ＩＳＩ序列,发现ＩＳＩ含有非稳定     

受损背根节神经元自发放电节律的整数倍模式及其动力学变化

本文记录了大鼠损伤背根节神经元的自发放电活动。采用背根节慢性压迫动物模型,记录慢性压迫手术后３－１０ｄ背根节的自发放电。在记录的１５６根纤维中,观察到１７根（占１１Ａ％）出现的动作电位峰峰间期以某一基础间期的整数倍模式出现的整数倍时间节律形式,其回归映射图为晶格状点阵结构,并且该时间形式受细胞膜上钠,钾通道的调控。     

用近似熵测量神经放电峰峰间期的复杂性

近似熵是用来测量信号复杂程度的非线性方法。为了研究神经放电序列的复杂性,用该方法及其改进方法对大鼠损伤坐崩神经模型、大鼠脑薄片视上核神经元自发放电模型、背根节自发放电模型峰峰间期以及Rose-Hindmarsh理论神经元模型分叉数据进行了动态测量。结果表明,近似熵可以定量反映多种神经放电序列复杂性的变化,是一种较为有效的复杂性序量方法。     

混沌放电的可兴奋性细胞对外界刺激反应敏感的动力学机制

在大鼠损伤背根节神经元受到去甲肾上腺(NE)、四乙基胺(TEA)和高浓度钙等剌激的实验中,观察到非周期放电的神经元明显地比周期放电的神经元对外界刺激的反应敏感程度高。现有的结果表明许多非周期放电的神经元实际上表现为确定性的混沌运动,比如混沌尖峰放电、混沌簇放电以及整数倍放电等。以修正的胰腺B细胞Chay模型为例,通过对其分岔结构的分析和对构成混沌吸引子的基本骨架的不稳定周期轨道的计算,揭示了分岔、激变和混沌运动对参数敏感依赖性是该现象产生的动力学机制。同时指出以往使用平均发放率来刻划可兴奋性细胞放电活动存在的缺陷,提出了一种新的利用周期轨道信息的刻划方法。     

藜芦碱引起神经元放电峰峰间期慢波振荡

为了研究Na通道失活门与受损背根节神经元放电型式的关系,在大鼠背根节慢性压迫模型上记录单纤维自发放电,观察与分析了Na通道失活门抑制剂藜芦碱（veratridine）引起峰峰间期慢波振荡的型式的特征。结果表明：在阻断Na通道失活门之后,受损背根节神经元产生的慢波振荡具有变化幅度大和振荡时程长的特征,可分成Ⅴ,倒П,整数倍,弥散和复合等5种基本形式。     

损伤神经自发放电节律变化中的混沌与阵发现象

为阐明损伤神经自发放电的动力学机制,长时间顺序记录大鼠损伤坐骨神经单纤维自发放电的动作电位间期序列（ＩＳＩ）。在损伤位点应用钾通道阻断剂ＴＥＡ,发现了周期一与周期二之间存在混沌的节律形式,并初步探讨了在这种情况下进入混沌的道路。应用分叉图、回归映象、功率谱等非线性动力学方法分析和对比了实验与数学模型中的非线性现象,使实验结果的可靠性得到了进一步的证明。     

损伤神经自发放电节律变化中的混沌与降发现象

秋阐明损伤神经自发放电的动力学机制，长时间顺序记录大鼠损伤坐骨神经单纤维自发放电的动作电位间期序列（ＩＳＩ）。在损伤位点应用钾通道阻断剂ＴＥＡ，发现了周期一与周期二之间存在混沌的节律形式，并初步探讨了在这种情况下进入混沌的道路。应用分叉图、回归映象、功率谱等非线性动力学方法分析和对比了实验与数学模型中的非线性现象，使实验结果的可靠性得到了进一步的证明。     

损伤神经元自发放电的整数倍节律及其动力学机制

实验采用大鼠背根节慢性压迫动物模型,记录术后３～１０天背根节的自发放电,在１５６根纤维中观察到１７根（１１％）出现的动作电位峰峰间期以某一基础间期的整数倍出现的时间节律形式,其回归映射图为晶格状点阵结构。同时观察到Ｎａ＾＋通道特异阻剂ＴＴＸ和Ｋ＾＋通道阻断剂４－ＡＰ能对整数倍放电节律产生影响。结果表明,看似不规则的整倍数放电时间序列是有着内在的结构和规律性的, 膜上通道和环境的状态决定。建立针对本     

大鼠脊髓背角神经元痛放电确定性行为的年龄相关变化

为阐明脊髓背角神经元痛放电的年龄相关的动力学变化,本研究采用非线性预报方法,对两组不同年龄大鼠(成年青龄鼠3～4月龄,老年鼠＞22月龄)组织损伤诱发的脊髓背角神经元痛放电峰峰间期序列进行了确定性行为的定量分析.结果显示,皮下注入蜜蜂毒,在两组大鼠均诱发脊髓背角广动力域神经元长时程放电,而老龄大鼠的痛放电峰峰间期序列表现出更高的可确定性.本研究表明,单个神经元的痛放电动力学在整个生命过程中并不是恒定不变的,伤害性神经元活动的年龄相关动力学变化可能是老年人群中多样化痛反应的内在机制之一.     

A novel bursting mechanism of type a neurons in injured dorsal root ganglia

Using intracellular recording in vivo, the bursting behaviors were investigated in the neurons of chronically compressed dorsal root ganglia of the adult rat. In most cases, the first spike of a burst emerged from amplitude-increasing damped subthreshold membrane potential oscillation (SMPO) and the discharge terminated by an amplitude-decreasing damped SMPO. The rhythms of these bursting behaviors are all irregular. Since some researchers found that the stochastic dynamics can also produce similar bursting pattern, the deterministic dynamics of interevent interval (IEI) series obtained from raw membrane potential recording was detected by extraction of the hierarchy of unstable periodic orbits (UPOs) in the windowed IEI series. The results showed a number of statistically significant UPOs of order-one, order-two, and order-three. These orbits form a complex but predictable lattice of regions in which the dynamics of the bursting occurrence is deterministic. Based on a complete classification scheme, the investigated bursting can be depicted by the elliptic bursting dynamics. The significance of the finding that a neuron in the injured dorsal root ganglion has such dynamics is also discussed.     

藜芦碱和乌头碱在受损背根节神经元诱发不同的放电模式

为了研究钠通道失活门阻断后受损背根节神经元放电模式的变化特征,在大鼠背根节慢性压迫模型上采用单纤维技术记录A类神经元的自发放电。藜芦碱和乌头碱是钠通道失活门的抑制剂,但二者作用于不同的位点,前者结合于D2-S6,后者结合于D3-S6。我们比较了这两种试剂引发的放电模式。结果发现,在同一神经元,藜芦碱(1．5～5．0μmol／L)可以引起放电峰峰间期的慢波振荡,即峰峰间期由大逐渐减小,然后又逐渐增大,形成重复的振荡波形,每个振荡持续约数十秒至数分钟：而乌头碱(10～200μmol／L)则引起强直性放电,即峰峰间期逐渐减小,然后维持在一个稳定的水平。这两种不同的放电模式不因背景放电或试剂浓度的不同而发生明显的改变。实验结果表明,藜芦碱和乌头碱在受损的背根节神经元可以引发不同的放电模式,这可能与它们结合于钠通道上不同位点的抑制作用有关。     

Noise enhances subthreshold oscillations in injured primary sensory neurons

Noise can play a constructive role in the detection of weak signals in various kinds of peripheral receptors and neurons. What the mechanism underlying the effect of noise is remains unclear. Here, the perforated patch-clamp technique was used on isolated cells from chronic compression of the dorsal root ganglion (DRG) model. Our data provided new insight indicating that, under conditions without external signals, noise can enhance subthreshold oscillations, which was observed in a certain type of neurons with high-frequency (20-100 Hz) intrinsic resonance from injured DRG neurons. The occurrence of subthreshold oscillation considerably decreased the threshold potential for generating repetitive firing. The above effects of noise can be abolished by blocking the persistent sodium current (I(Na, P)). Utilizing a mathematical neuron model we further simulated the effect of noise on subthreshold oscillation and firing, and also found that noise can enhance the electrical activity through autonomous stochastic resonance. Accordingly, we propose a new concept of the effects of noise on neural intrinsic activity, which suggests that noise may be an important factor for modulating the excitability of neurons and generation of chronic pain signals.     

Differentiation state determines neural effects on microvascular endothelial cells

Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells.     

Strategies to repair lost sensory connections to the spinal cord

Failure of injured axons to regenerate in the central nervous system (CNS) is the main obstacle for repair of stroke and traumatic injuries to the spinal cord and sensory roots. This regeneration failure is high-lighted at the dorsal root transitional zone (DRTZ), the boundary between the peripheral (PNS) and central nervous system where sensory axons enter the spinal cord. Injured sensory axons regenerate in the PNS compartment of the dorsal root but are halted as soon as they reach the DRTZ. The failure of regenerating dorsal root axons to re-enter the mature spinal cord is a reflection of the generally nonpermissive nature of the CNS environment, in contrast to the regeneration supportive properties of the PNS. The dorsal root injury paradigm is therefore an attractive model for studying mechanisms underlying CNS regeneration failure in general and how to overcome the hostile CNS environment. Here we review the main lines that have been pursued to achieve growth of injured dorsal root axons into the spinal cord: (i) modifying the inhibitory nature of the DRTZ by breaking down or blocking the effect of growth repelling molecules, (ii) stimulate elongation of injured dorsal root axons by a prior conditioning lesion or administration of specific growth factors, (iii) implantation of olfactory ensheathing cells to provide a growth supportive cellular terrain at the DRTZ, and (iv) replacing the regeneration deficient adult dorsal root ganglion neurons with embryonic neurons or neural stem cells.     

Do birds differentiate between white noise and deterministic chaos?

Noisy, unpredictable sounds are often present in the vocalizations of fearful and stressed animals across many taxa. A variety of structural characteristics, called nonlinear acoustic phenomena, that include subharmonics, rapid frequency modulations, and deterministic chaos are responsible for the harsh sound quality of these vocalizations. Exposure to nonlinear sound can elicit increased arousal in birds and mammals. Past experiments have used white noise to test for effects of deterministic chaos on perceivers. However, deterministic chaos differs structurally from white noise (i.e., random signal with equal energy at all frequencies), and unlike white noise, may differ dramatically depending on how it is produced. In addition, the subtle structural variation of chaos may not be distinguishable in the environment due to the attenuation and degradation of sound over distance and different habitat types. We designed two experiments to clarify whether American robins (Turdus migratorius) and warbling vireos (Vireo gilvus) discriminate between white noise and deterministic chaos. We broadcast and re‐recorded white noise and two exemplars of deterministic chaos—one generated with a Chua oscillator and the other generated using a logistic equation—at 1, 10, 20, 30, 40, and 80 m across open and forested habitat and used spectrogram correlations to compare stimuli along this degradational gradient. We found that sounds degraded similarly in both habitats when compared to a reference distance of 1 m. Comparing pairs of stimuli across distances suggested that Chua chaos was more easily distinguishable from noise and logistic chaos. In addition, all stimuli became more distinctive over increased distance. The second experiment tested behavioral responses of robins and warbling vireos to control sounds of tropical kingbird (Quiscalus mexicanus), white noise, and two exemplars of deterministic chaos (Chua and logistic). Neither American robins nor warbling vireos responded differently to at least two types of deterministic chaos and white noise, validating previous playback studies that used white noise as a surrogate for deterministic chaos. Uniform responses to a variety of nonlinear features in these birds possibly reflect error management in alarm signal detection.     

Nerve growth factor-induced stimulation of dorsal root ganglion/spinal cord co-grafts in oculo: enhanced survival and growth of CGRP-immunoreactive sensory neurons

Intraocular co-grafts of rat fetal spinal cord and dorsal root ganglia were used to examine the enhanced survival, growth, and differentiation of sensory neurons by nerve growth factor. E14 lumbar spinal segments were implanted into the anterior eye chamber of capsaicin-pretreated rats. Two weeks later, an E14 dorsal root ganglion was implanted beside the spinal cord graft. Nerve growth factor or vehicle was injected weekly for 4 weeks into the anterior eye chamber. Co-grafts were examined weekly and, at 6 weeks, processed for calcitonin gene-related peptide (CGRP) immunofluorescence. No differences in overall size were determined for the grafts. Co-grafts treated with nerve growth factor contained many more CGRP neurons (19.4 cells/20 microm) that were significantly larger (mean 764 microm2) than neurons from control co-grafts (8.6 cells/20 microm; mean 373 microm2). In co-grafts treated with nerve growth factor, CGRP-immunoreactive fibers were extensive in the dorsal root ganglion, adjacent iris, and spinal cord compared to control co-grafts. A few CGRP-positive motoneurons were observed in the spinal cord, but no differences in number or size of motoneurons were found. The current report demonstrates that spinal cord and dorsal root ganglia can be co-grafted in oculo for long periods of time. Many dorsal root ganglion neurons survive and send peripheral processes into the iris and central processes into the spinal cord under the influence of exogenous nerve growth factor. The intraocular graft paradigm can be of use to further examine the role of neurotrophic factors in regulating or modulating dorsal root ganglion and spinal cord neurons.