基于小波变换和非线性能量算子的神经元放电检测

微电极导向的立体定向手术中,微电极记录的神经元放电信号噪声干扰严重,信噪比变化大,影响着神经元放电脉冲的分析。利用小波变换和非线性能量算子相结合的一种新的方法能检测出神经元放电。通过对临床不同病人、不同特点的神经元放电信号处理,结果表明:该方法能成功地检测出细胞放电,提取出放电波形。     

神经核团异常放电的数值模拟与FPGA实现

进行神经核团网络异常放电的数值模拟以及硬件实现。方法:选用Izhikevich模型模拟单个神经元放电,通过化学突触连接各神经元搭建神经核团网络,进而在FPGA上实现神经核团放电。对比Izhikevich模型在Simulink和DSP Builder两种软件中建模的相对标准误差,并分析各神经核团的放电特性。结果:两种软件中各神经核团的仿真结果相对标准误差均小于0.1,验证了建模的一致性。通过计算丘脑的中继可靠性指标RI=0.3<0.6,证明搭建的神经核团网络可以模拟帕金森病的一种放电状态。结论:模拟神经核团的异常放电对替代动物活体实验、探究神经性疾病的治疗方法和脑机接口研究等具有重要意义。     

一种用计算机处理电生理信号的接口电路

在电生理实验中,用微电极测取神经元或神经纤维放电脉冲信号,经放大后可以在示波器上显示出来或拍成相片再进行分析统计处理。也可以用磁带记录器记录下来,利用微型计算机做进一步的处理。但由于这种生理信号是一种信噪比很差的信号,其中不仅有大量的噪声,而且有时还混杂着幅度很大的电钟伪迹信号。因此无法直接通过微型计算机的通用接口输入到计算中去进行分析处理。本文介绍的这种接口电路可以对电生理信号进行预处理,然后再输入到单板计算机或微型计算机中去做进一步统计分析处理。     

离体大鼠海马神经元自发放电活动一般特征的研究

观察离体大鼠海马锥体细胞的生理电发放模式.在脑脊液孵育下,将玻璃微电极插入到离体大鼠海马脑片锥体细胞附近,进行胞外电脉冲记录,微机记录并保存电信号.共观察到海马部神经元自发放电主要呈5种特征,分别为不规则发放、单波规则发放、紧张发放、阵发排放及周期排放型等形式.说明神经元的生理电发放模式可能与细胞的排列次序、生理应答呈一定的相关性.     

脑内θ振荡与学习记忆的关系研究进展

脑电图(EEG)反映了所记录脑区神经元集群整体的规则化、同步化突触后电活动。这种同步化放电往往以特定频率在脑内播散，协调不同神经核团共同发挥作用。不同特征的脑电波形可用以反映大脑所处的特定功能状态，其中以3～10 Hz的θ振荡为优势频段的脑电活动在学习记忆的编码、巩固和提取阶段中均发挥重要功能。本篇综述主要对额叶和海马中θ振荡的产生及其在学习记忆过程中的作用进行讨论。     

用辣根过氧化物酶溶液低温快速充灌玻璃微电极的方法(摘要)

近年来不少人将电生理学方法与神经解剖学方法结合起来研究中枢神经系统。如用充灌有HRP溶液的玻璃电极记录神经细胞的电活动后,再电泳HRP,以了解记录部位神经核团或神经元的功能、形态及神经联系。但是,在常温下用HRP溶液充灌玻璃微电极常在尖端出现气泡,可使记录不稳定或是通过的电流特性不稳定。我们参照Lewis B. Haberly和James M Bower(1981)提出的快速充灌玻璃微电极的方法,结合我们的条件,稍加改进作了一些试验。该法是在低温下进行充灌。其原理是温度降低时,可使表面张力增加,从而     

急性饮酒对小鼠海马 CA1区锋电位的影响

观察研究急性饮酒前后,小鼠海马区锋电位（Spike）的放电频率及峰峰间期等的变化,描述并分析清醒状态及急性饮酒后小鼠海马区神经元电信号的特征差异,评价急性饮酒对小鼠海马区记忆功能的影响。以 ICR 小鼠为实验对象,分成急性饮酒组（P 组）和生理盐水对照组（C 组）。在小鼠海马 CA1区植入8通道微电极阵列,利用神经信号处理采集系统 Cerebus 记录急性饮酒前后小鼠海马 CA1区神经电信号,分析比较海马区神经元放电频率以及锋电位间隔直方图（Interspike Interval Histograms ,ISI）的变化。P 组与 C 组比较,P 组平均放电率小于 C 组;与清醒状态下比较,急性饮酒后小鼠海马区神经元放电频率变低,然后随着时间逐渐增强,慢慢恢复;ISI 值从较为集中变为较为分散。急性饮酒后小鼠海马区神经元自发放电在放电频率、ISI 等神经信号的特征方面存在明显差异。急性饮酒可抑制小鼠海马区神经元放电,抑制小鼠记忆功能。     

苍白球损毁术中微电极的位置识别方法

在治疗帕金森病的苍白球损毁外科手术中,微电极在苍白球中的位置只能通过分析微电极测量的细胞放电特征,依靠主观经验判定。我们以临床微电极信号为基础,利用峰峰时间间隔因子,提出了客观定量的识别微电极位置的方法。该方法能有效的识别出沿微电极针道苍白球组织的变化以及针道是否偏离,识别结果与苍白球解剖结构和手术情况相吻合,此方法可用于临床手术导向。     

时间序列分析方法在神经放电信号研究中的应用

本文提出应用时间序列分析的方法来研究神经放电脉冲信号的特性。首先对神经放电脉冲间隔序列拟合自回归模型,然后求自回归模型的格林函数和功率谱密度函数。从而探求神经放电信号的某些规律性(如动态特性、记忆特性和周期性等等)。     

有髓神经纤维传入对网状大细胞核及中缝大核神经元电活动的影响

网状大细胞核(RMC)是近年来引起人们关注的一个痛觉调制核团。但迄今尚缺乏对该核团神经元对躯体神经传入反应特点的研究,而且对该核是独立的核团,还是中缝大核(NRM)的两侧延展尚有争议。本工作就是以不同有髓纤维兴奋输入,用微电极方法记录RMC神经元的反应,并且与NRM神经元的反应进行比较,看是否一致。     

Conditional spike backpropagation generates burst discharge in a sensory neuron

Backpropagating dendritic Na(+) spikes generate a depolarizing afterpotential (DAP) at the soma of pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric fish. Repetitive spike discharge is associated with a progressive depolarizing shift in somatic spike afterpotentials that eventually triggers a high-frequency spike doublet and subsequent burst afterhyperpolarization (bAHP). The rhythmic generation of a spike doublet and bAHP groups spike discharge into an oscillatory burst pattern. This study examined the soma-dendritic mechanisms controlling the depolarizing shift in somatic spike afterpotentials, and the mechanism by which spike doublets terminate spike discharge. Intracellular recordings were obtained from ELL pyramidal somata and apical dendrites in an in vitro slice preparation. The pattern of spike discharge was equivalent in somatic and dendritic regions, reflecting the backpropagation of spikes from soma to dendrites. There was a clear frequency-dependent threshold in the transition from tonic to burst discharge, with bursts initiated when interspike intervals fell between approximately 3-7 ms. Removal of all backpropagating spikes by dendritic TTX ejection revealed that the isolated somatic AHPs were entirely stable at the interspike intervals that generated burst discharge. As such, the depolarizing membrane potential shift during repetitive discharge could be attributed to a potentiation of DAP amplitude. Potentiation of the DAP was due to a frequency-dependent broadening and temporal summation of backpropagating dendritic Na(+) spikes. Spike doublets were generated with an interspike interval close to, but not within, the somatic spike refractory period. In contrast, the interspike interval of spike doublets always fell within the longer dendritic refractory period, preventing backpropagation of the second spike of the doublet. The dendritic depolarization was thus abruptly removed from one spike to the next, allowing the burst to terminate when the bAHP hyperpolarized the membrane. The transition from tonic to burst discharge was dependent on the number and frequency of spikes invoking dendritic spike summation, indicating that burst threshold depends on the immediate history of cell discharge. Spike frequency thus represents an important condition that determines the success of dendritic spike invasion, establishing an intrinsic mechanism by which backpropagating spikes can be used to generate a rhythmic burst output.     

Electrophysiological properties of hypoglossal motoneurons of guinea-pigs studied in vitro

Intracellular recordings were made from the hypoglossal nuclear complex in brain slices from guinea-pigs. Retrograde transport of horseradish peroxidase from the tongue confirmed the identity of the visually identified hypoglossal nucleus. Eighteen neurons were stained by intracellular electrophoresis of Lucifer Yellow through the recording pipette. Two types of neurons were encountered, motoneurons with maximal discharge rates of 90 Hz and another type with maximal discharge rates of 250 Hz. Motoneurons were prevalent in the hypoglossal nucleus and the other type prevailed in the adjoining nucleus prepositus hypoglossi. In both nuclei the two types were mixed. Antidromic spikes elicited from hypoglossal root fibres had initial segment and somatodendritic components. Electrical stimulation of the reticular matter dorsolateral to the hypoglossal nucleus elicited excitatory postsynaptic potentials and strychnine sensitive inhibitory postsynaptic potentials. Motoneurons responded to depolarizing current pulses with a train of spikes. The initial spike interval was much shorter than the rest and fast adaptation occurred over three to four intervals. Slow adaptation was most prominent when the neuron was depolarized and discharged at a high rate. High threshold calcium spikes were evoked by depolarizing pulses when sodium spikes were blocked by tetrodotoxin and the potassium conductance reduced by tetraethylammonium bromide. Motoneurons discharged in a single range, inflections on the frequency-current plot being absent. Spikes and spike trains evoked by depolarizing pulses were followed by afterhyperpolarizations with fast and slow parts. The fast phase was eliminated by tetraethyl-ammonium bromide, possibly because the delayed rectifier was involved. A calcium dependent potassium conductance was probably involved in the slow phase, because it was sensitive to inorganic calcium blockers. The amplitude of the afterhyperpolarization following trains of spikes depended on the frequency of the preceding spikes. At constant frequency, the amplitude depended, in addition, on the strength of stimuli arising from different hyperpolarized potentials. Afterdepolarizing potentials were absent. Lissajous plots of double ramp current stimulation showed anomalous rectification between resting potential and spike threshold. The rectification was sensitive to inorganic calcium blockers. Subthreshold responses showed initial sags and rebound responses in all healthy cells and these were eliminated by caesium. Barium, substituted for calcium, unleashed a depolarizing plateau potential sensitive to tetrodotoxin, indicating the presence of a persistent sodium conductance.

The membrane of hypoglossal motoneurons contains voltage dependent conductances in the voltage range around resting potential and spike threshold. These conductances provide for effective switching between the discharging and the non-discharging state of the motoneuron.     

基于数学形态学与核主成分分析的峰电位检测与分类方法

目的 为抑制高强度背景噪声及信号叠加的干扰,提高峰电位的检出率和分类的正确性,本文提出一种新的无监督方法.方法 首先,应用数学形态学的复合操作对信号进行降噪,采用定阈值提取峰电位.然后,小波变换和核主成分分析法（kernel principal components analysis,KPCA）相结合,对已提取的峰电位波形进行特征提取.最后,用改进的最小距离法实现峰电位分类.结果 仿真实验结果表明,此方法对于不同噪声强度的信号,峰电位检出率达94%,总分类正确率91%以上,其中大量叠加信号的分类正确率88%以上.结论 本方法能在有效抑制噪声的基础上,准确提取峰电位并有效分类.     

Persistent Na+ current modifies burst discharge by regulating conditional backpropagation of dendritic spikes

The estimation and detection of stimuli by sensory neurons is affected by factors that govern a transition from tonic to burst mode and the frequency characteristics of burst output. Pyramidal cells in the electrosensory lobe of weakly electric fish generate spike bursts for the purpose of stimulus detection. Spike bursts are generated during repetitive discharge when a frequency-dependent broadening of dendritic spikes increases current flow from dendrite to soma to potentiate a somatic depolarizing afterpotential (DAP). The DAP eventually triggers a somatic spike doublet with an interspike interval that falls inside the dendritic refractory period, blocking spike backpropagiation and the DAP. Repetition of this process gives rise to a rhythmic dendritic spike failure, termed conditional backpropagation, that converts cell output from tonic to burst discharge. Through in vitro recordings and compartmental modeling we show that burst frequency is regulated by the rate of DAP potentiation during a burst, which determines the time required to discharge the spike doublet that blocks backpropagation. DAP potentiation is magnified through a positive feedback process when an increase in dendritic spike duration activates persistent sodium current (I(NaP)). I(NaP) further promotes a slow depolarization that induces a shift from tonic to burst discharge over time. The results are consistent with a dynamical systems analysis that shows that the threshold separating tonic and burst discharge can be represented as a saddle-node bifurcation. The interaction between dendritic K(+) current and I(NaP) provides a physiological explanation for a variable time scale of bursting dynamics characteristic of such a bifurcation.     

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

Brief bursts of fast high-frequency action potentials are a signature characteristic of CA3 and CA1 pyramidal neurons. Understanding the factors determining burst and single spiking is potentially significant for sensory representation, synaptic plasticity and epileptogenesis. A variety of models suggest distinct functional roles for burst discharge, and for specific characteristics of the burst in neural coding. However, little in vivo data demonstrate how often and under what conditions CA3 and CA1 actually exhibit burst and single spike discharges. The present study examined burst discharge and single spiking of CA3 and CA1 neurons across distinct behavioral states (awake-immobility and maze-running) in rats. In both CA3 and CA1 spike bursts accounted for less than 20% of all spike events. CA3 neurons exhibited more spikes per burst, greater spike frequency, larger amplitude spikes and more spike amplitude attenuation than CA1 neurons. A major finding of the present study is that the propensity of CA1 neurons to burst was affected by behavioral state, while the propensity of CA3 to burst was not. CA1 neurons exhibited fewer bursts during maze running compared with awake-immobility. In contrast, there were no differences in burst discharge of CA3 neurons. Neurons in both subregions exhibited smaller spike amplitude, fewer spikes per burst, longer inter-spike intervals and greater spike amplitude attenuation within a burst during awake-immobility compared with maze running. These findings demonstrate that the CA1 network is under greater behavioral state-dependent regulation than CA3. The present findings should inform both theoretic and computational models of CA3 and CA1 function.     

Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation

The strength of synapses between auditory nerve (AN) fibers and ventral cochlear nucleus (VCN) neurons is an important factor in determining the nature of neural integration in VCN neurons of different response types. Synaptic strength was analyzed using cross-correlation of spike trains recorded simultaneously from an AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as chopper, primarylike, and onset using previously defined criteria, although onset neurons usually were not analyzed because of their low discharge rates. The correlograms showed an excitatory peak (EP), consistent with monosynaptic excitation, in AN-VCN pairs with similar best frequencies (49% 24/49 of pairs with best frequencies within +/-5%). Chopper and primarylike neurons showed similar EPs, except that the primarylike neurons had shorter latencies and shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical bushy cells were not observed, probably because of the low probability of recording from one. The small EPs observed in primarylike neurons, presumably spherical bushy cells, could be derived from small terminals that accompany end bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were consistent with the smaller synaptic terminals on multipolar and globular bushy cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of threshold, showing that VCN responses to steady tones shift from a 1:1 relationship between AN and VCN spikes at low sound levels to a more autonomous mode of firing at high levels. In the high level mode, the pattern of output spikes seems to be determined by the properties of the postsynaptic spike generator rather than the input spike patterns. The EP amplitudes did not change significantly when the presynaptic spike was preceded by either a short or long interspike interval, suggesting that synaptic depression and facilitation have little effect under the conditions studied here.     

Subthreshold oscillations generated by TTX-sensitive sodium currents in dorsal cochlear nucleus pyramidal cells

During intracellular recordings in rodent brainstem slice preparations, dorsal cochlear nucleus (DCN) pyramidal cells (PCs) exhibit characteristic discharge patterns to depolarizing current injection that depend on the membrane potential from which the responses are evoked. When depolarized from hyperpolarized potentials, PCs can respond with a short-latency action potential followed by a long silent interval (pauser) or a train of action potentials with a long latency (buildup). During the silent intervals in a pauser or a buildup response, the membrane potential slowly depolarizes towards spike threshold, often exhibiting distinct voltage oscillations of 1–2 mV before the first spike. The subthreshold voltage oscillations were investigated using whole cell recordings from DCN PCs in rat pup (P10–14) brainstem slices. The oscillations were unaffected by excitatory and inhibitory neurotransmitter antagonists, and were not temporally locked to the onset of the depolarization. The oscillations typically became larger as spike threshold was approached, and had a characteristic frequency between 40 and 100 Hz. In the presence of tetrodotoxin (TTX, 500 nM), the oscillations were significantly suppressed, and could not be evoked at any voltage below or above spike threshold. The oscillations were not blocked by phenytoin or Cd²⁺, but they were affected by prior activity in the neuron for approximately 1 s. We conclude that voltage-gated Na⁺ channels are required to generate membrane oscillations during the buildup phase. We suggest that the subthreshold oscillations play a role in controlling spike timing in PCs when the membrane potential slowly approaches, or hovers near, spike threshold.     

Whisker movements evoked by stimulation of single motor neurons in the facial nucleus of the rat

The lateral facial nucleus is the sole output structure whose neuronal activity leads to whisker movements. To understand how single facial nucleus neurons contribute to whisker movement we combined single-cell stimulation and high-precision whisker tracking. Half of the 44 stimulated neurons gave rise to fast whisker protraction or retraction movement, whereas no stimulation-evoked movements could be detected for the remainder. Direction, speed, and amplitude of evoked movements varied across neurons. Protraction movements were more common than retraction movements (n = 16 vs. n = 4), had larger amplitudes (1.8 vs. 0.3 degrees for single spike events), and most protraction movements involved only a single whisker, whereas most retraction movements involved multiple whiskers. We found a large range in the amplitude of single spike-evoked whisker movements (0.06-5.6 degrees ). Onset of the movement occurred at 7.6 (SD 2.5) ms after the spike and the time to peak deflection was 18.2 (SD 4.3) ms. Each spike reliably evoked a stereotyped movement. In two of five cases peak whisker deflection resulting from consecutive spikes was larger than expected when based on linear summation of single spike-evoked movement profiles. Our data suggest the following coding scheme for whisker movements in the facial nucleus. 1) Evoked movement characteristics depend on the identity of the stimulated neuron (a labeled line code). 2) The facial nucleus neurons are heterogeneous with respect to the movement properties they encode. 3) Facial nucleus spikes are translated in a one-to-one manner into whisker movements.     

Comparative analysis of cerebellar unit discharge patterns in the decerebrate cat during passive movements

Summary 1) The present experiments were undertaken to study how information about the parameters of a passive movement is processed at different neuronal levels of the cat cerebellar cortex. The analysis has been performed by recording extracellularly in the intermediate part of the cerebellar anterior lobe from presumed mossy fibres, presumed granule cells, and Purkinje cells with simple spikes and complex spikes. 2) The discharge patterns obtained during passive movements of the cat's forepaw were characterized by components which could be related to dynamic or static parameters of the movement. With respect to the occurrence of dynamic responses, patterns were classified according to a statistically derived measure in three different types. By using the same statistical measure, discharge patterns were additionally classified into two subgroups according to their response components reflecting static parameters. Within the patterns a clearcut relationship between dynamic and static components was observed. The corresponding distributions are shown and discussed. 3) A very interesting result of the classification of cerebellar discharge patterns is that the distribution of the different types depended on the level of integration within the cerebellar cortex. Patterns of the low scale integrated cerebellar input (mossy fibre-system), as well as those of granule cells (the first cerebellar computational niveau), reflected both static and dynamic movement parameters. At the Purkinje cell level (a level with a high degree of convergence) the discharge patterns are characterized predominantly by dynamic responses. 4) The interrelationship between complex- and simple spikes of Purkinje cells was tested by different methods: a) By analyzing the paired values of the mean complex-(CS) and simple spike (SS) discharge probabilities of 110 Purkinje cells a scatter was obtained, indicating an underlying hyperbolic relation (prob(CS) = a/(prob(SS))^b). Thus, a high CS discharge probability is accompanied by a low SS probability and vice versa, b) The timelocked complex- and simple spike responses were studied by comparing the similarity of their responses. All combinations of complex- and simple spike patterns were observed, ranging from a sign correct similarity to a mirror image similarity. The distribution of the measure for similarity shows that the mirror image predominated, c) The individual simple spike discharge probability is characterized by a pause evoked by the occurrence of a complex spike event. The simple spike discharge probabilities during an interval preceeding and following a complex spike event were compared. A post climbing pause coefficient was defined as a measure for the effectiveness of the complex spike event. No relationship between these coefficients and the above mentioned measure for similarity was found. Hence, for the Purkinje cell discharging with the simple spikes independent spike generating processes have to be assumed. 5) From these results it can be derived that cerebellar discharge patterns can be classified with respect to responses to static and dynamic parameters of passive limb movements. Based on this classification it appears that the distribution of responses to static and dynamic parameters depends on the computational level within the cerebellar cortex. If both static and dynamic parameters are conveyed by a single unit, a clear relationship between the response components could be observed. However, this effect was independently found at all cerebellar cortical computational levels indicating a functional principle of processing a pair of movement parameters. The interrelation of complex- and simple spike responses to passive movement was further studied. Since transients of complex- and simple spike patterns were observed ranging from two almost identical patterns to mirror image like patterns, it is assumed that under physiological conditions one of the tasks of the climbing fibre system consists of tuning the simple spike discharge according to the peripheral requirements.