Sustained firing in auditory cortex evoked by preferred stimuli

It has been well documented that neurons in the auditory cortex of anaesthetized animals generally display transient responses to acoustic stimulation, and typically respond to a brief stimulus with one or fewer action potentials. The number of action potentials evoked by each stimulus usually does not increase with increasing stimulus duration. Such observations have long puzzled researchers across disciplines and raised serious questions regarding the role of the auditory cortex in encoding ongoing acoustic signals. Contrary to these long-held views, here we show that single neurons in both primary (area A1) and lateral belt areas of the auditory cortex of awake marmoset monkeys (Callithrix jacchus) are capable of firing in a sustained manner over a prolonged period of time, especially when they are driven by their preferred stimuli. In contrast, responses become more transient or phasic when auditory cortex neurons respond to non-preferred stimuli. These findings suggest that when the auditory cortex is stimulated by a sound, a particular population of neurons fire maximally throughout the duration of the sound. Responses of other, less optimally driven neurons fade away quickly after stimulus onset. This results in a selective representation of the sound across both neuronal population and time.     

Local sleep and learning

Human sleep is a global state whose functions remain unclear. During much of sleep, cortical neurons undergo slow oscillations in membrane potential, which appear in electroencephalograms as slow wave activity (SWA) of <4 Hz. The amount of SWA is homeostatically regulated, increasing after wakefulness and returning to baseline during sleep. It has been suggested that SWA homeostasis may reflect synaptic changes underlying a cellular need for sleep. If this were so, inducing local synaptic changes should induce local SWA changes, and these should benefit neural function. Here we show that sleep homeostasis indeed has a local component, which can be triggered by a learning task involving specific brain regions. Furthermore, we show that the local increase in SWA after learning correlates with improved performance of the task after sleep. Thus, sleep homeostasis can be induced on a local level and can benefit performance.     

A putative flip-flop switch for control of REM sleep

Rapid eye movement (REM) sleep consists of a dreaming state in which there is activation of the cortical and hippocampal electroencephalogram (EEG), rapid eye movements, and loss of muscle tone. Although REM sleep was discovered more than 50 years ago, the neuronal circuits responsible for switching between REM and non-REM (NREM) sleep remain poorly understood. Here we propose a brainstem flip-flop switch, consisting of mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum. Each side contains GABA (gamma-aminobutyric acid)-ergic neurons that heavily innervate the other. The REM-on area also contains two populations of glutamatergic neurons. One set projects to the basal forebrain and regulates EEG components of REM sleep, whereas the other projects to the medulla and spinal cord and regulates atonia during REM sleep. The mutually inhibitory interactions of the REM-on and REM-off areas may form a flip-flop switch that sharpens state transitions and makes them vulnerable to sudden, unwanted transitions-for example, in narcolepsy.     

黑质注射鱼藤酮对大鼠行为和丘脑VL核自发放电的影响

研究中脑黑质注射鱼藤酮对大鼠行为和丘脑VL核神经元电活动的影响.运用网格、斜板和开阔试验检测大鼠行为改变；微电极记录丘脑VL核神经元自发电活动.鱼藤酮脑内注射28 d后，大鼠在网格上的移动潜伏期明显增长，沿斜板下滑次数显著增多，自主活动减少，而静止性蹲坐时间显著增多；丘脑VL核神经元自发放电频数显著降低，电频谱峰向低频区聚集，Ⅰ型簇状放电型式减少，更多的表现为规律型放电或Ⅱ型簇状放电.结果表明黑质注射鱼藤酮能诱发大鼠出现肌僵直、行动迟缓、震颤等类帕金森病征状，丘脑VL核神经元自发放电活动相应减弱，放电型式有所改变.     

Preplay of future place cell sequences by hippocampal cellular assemblies

During spatial exploration, hippocampal neurons show a sequential firing pattern in which individual neurons fire specifically at particular locations along the animal's trajectory (place cells). According to the dominant model of hippocampal cell assembly activity, place cell firing order is established for the first time during exploration, to encode the spatial experience, and is subsequently replayed during rest or slow-wave sleep for consolidation of the encoded experience. Here we report that temporal sequences of firing of place cells expressed during a novel spatial experience occurred on a significant number of occasions during the resting or sleeping period preceding the experience. This phenomenon, which is called preplay, occurred in disjunction with sequences of replay of a familiar experience. These results suggest that internal neuronal dynamics during resting or sleep organize hippocampal cellular assemblies into temporal sequences that contribute to the encoding of a related novel experience occurring in the future.     

Boosting slow oscillations during sleep potentiates memory

There is compelling evidence that sleep contributes to the long-term consolidation of new memories. This function of sleep has been linked to slow (<1 Hz) potential oscillations, which predominantly arise from the prefrontal neocortex and characterize slow wave sleep. However, oscillations in brain potentials are commonly considered to be mere epiphenomena that reflect synchronized activity arising from neuronal networks, which links the membrane and synaptic processes of these neurons in time. Whether brain potentials and their extracellular equivalent have any physiological meaning per se is unclear, but can easily be investigated by inducing the extracellular oscillating potential fields of interest. Here we show that inducing slow oscillation-like potential fields by transcranial application of oscillating potentials (0.75 Hz) during early nocturnal non-rapid-eye-movement sleep, that is, a period of emerging slow wave sleep, enhances the retention of hippocampus-dependent declarative memories in healthy humans. The slowly oscillating potential stimulation induced an immediate increase in slow wave sleep, endogenous cortical slow oscillations and slow spindle activity in the frontal cortex. Brain stimulation with oscillations at 5 Hz--another frequency band that normally predominates during rapid-eye-movement sleep--decreased slow oscillations and left declarative memory unchanged. Our findings indicate that endogenous slow potential oscillations have a causal role in the sleep-associated consolidation of memory, and that this role is enhanced by field effects in cortical extracellular space.     

Spontaneously emerging cortical representations of visual attributes

Spontaneous cortical activity--ongoing activity in the absence of intentional sensory input--has been studied extensively, using methods ranging from EEG (electroencephalography), through voltage sensitive dye imaging, down to recordings from single neurons. Ongoing cortical activity has been shown to play a critical role in development, and must also be essential for processing sensory perception, because it modulates stimulus-evoked activity, and is correlated with behaviour. Yet its role in the processing of external information and its relationship to internal representations of sensory attributes remains unknown. Using voltage sensitive dye imaging, we previously established a close link between ongoing activity in the visual cortex of anaesthetized cats and the spontaneous firing of a single neuron. Here we report that such activity encompasses a set of dynamically switching cortical states, many of which correspond closely to orientation maps. When such an orientation state emerged spontaneously, it spanned several hypercolumns and was often followed by a state corresponding to a proximal orientation. We suggest that dynamically switching cortical states could represent the brain's internal context, and therefore reflect or influence memory, perception and behaviour.     

Turning on and off recurrent balanced cortical activity

The vast majority of synaptic connections onto neurons in the cerebral cortex arise from other cortical neurons, both excitatory and inhibitory, forming local and distant 'recurrent' networks. Although this is a basic theme of cortical organization, its study has been limited largely to theoretical investigations, which predict that local recurrent networks show a proportionality or balance between recurrent excitation and inhibition, allowing the generation of stable periods of activity. This recurrent activity might underlie such diverse operations as short-term memory, the modulation of neuronal excitability with attention, and the generation of spontaneous activity during sleep. Here we show that local cortical circuits do indeed operate through a proportional balance of excitation and inhibition generated through local recurrent connections, and that the operation of such circuits can generate self-sustaining activity that can be turned on and off by synaptic inputs. These results confirm the long-hypothesized role of recurrent activity as a basic operation of the cerebral cortex.     

Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids

Neocortical GABA-containing interneurons form complex functional networks responsible for feedforward and feedback inhibition and for the generation of cortical oscillations associated with several behavioural functions. We previously reported that fast-spiking (FS), but not low-threshold-spiking (LTS), neocortical interneurons from rats generate a fast and precise self-inhibition mediated by inhibitory autaptic transmission. Here we show that LTS cells possess a different form of self-inhibition. LTS, but not FS, interneurons undergo a prominent hyperpolarization mediated by an increased K+-channel conductance. This self-induced inhibition lasts for many minutes, is dependent on an increase in intracellular [Ca2+] and is blocked by the cannabinoid receptor antagonist AM251, indicating that it is mediated by the autocrine release of endogenous cannabinoids. Endocannabinoid-mediated slow self-inhibition represents a powerful and long-lasting mechanism that alters the intrinsic excitability of LTS neurons, which selectively target the major site of excitatory connections onto pyramidal neurons; that is, their dendrites. Thus, modulation of LTS networks after their sustained firing will lead to long-lasting changes of glutamate-mediated synaptic strength in pyramidal neurons, with consequences during normal and pathophysiological cortical network activities.     

Attractor dynamics of network UP states in the neocortex

The cerebral cortex receives input from lower brain regions, and its function is traditionally considered to be processing that input through successive stages to reach an appropriate output. However, the cortical circuit contains many interconnections, including those feeding back from higher centres, and is continuously active even in the absence of sensory inputs. Such spontaneous firing has a structure that reflects the coordinated activity of specific groups of neurons. Moreover, the membrane potential of cortical neurons fluctuates spontaneously between a resting (DOWN) and a depolarized (UP) state, which may also be coordinated. The elevated firing rate in the UP state follows sensory stimulation and provides a substrate for persistent activity, a network state that might mediate working memory. Using two-photon calcium imaging, we reconstructed the dynamics of spontaneous activity of up to 1,400 neurons in slices of mouse visual cortex. Here we report the occurrence of synchronized UP state transitions ('cortical flashes') that occur in spatially organized ensembles involving small numbers of neurons. Because of their stereotyped spatiotemporal dynamics, we conclude that network UP states are circuit attractors--emergent features of feedback neural networks that could implement memory states or solutions to computational problems.     

基于时窗复杂度序列的睡眠脑电分析

运用时窗复杂度序列来分析睡眠脑电,减少了非平稳性及状态空间的不均匀性造成的脑状态信息的丢失,在一定程度上克服了复杂度的自身的局限,有助于不同睡眠期状态特征的提取.另外本文采用ICA、小波变换等方法对脑电进行预处理,实验表明它们能有效地去除脑电中的一些生理干扰,有利于提高复杂度算法在睡眠分期应用中的精确度.     

家兔胃消化性运动及收缩波分类

对 21 只带有胃瘘管(重2.5克)的兔,用气球法记录胃运动;另5只兔装有十二指肠再返瘘管(重2.3克/对),以检测进食前后胃排空量的动态变化。结果表明:兔胃呈持续性运动,但有低潮期(持续几分到十几分钟),表现为紧张度低平,收缩波幅明显减小并偶有高波出现。胃收缩波型分三类:快节律波(即20秒节律波)、慢节律波和长周期紧张性收缩。进食后胃排空量增多,各类波特别是慢节律波中三种波的数量比例分别出现明显增大或减小,这提示在促进胃排空方面,几种波分别起着不同的作用。本文对兔胃运动波型的分类,不是完全按照传统标准——单纯根据形态,而是掺进了“功能”这一因素。     

Rapid developmental switch in the mechanisms driving early cortical columnar networks

The immature cerebral cortex self-organizes into local neuronal clusters long before it is activated by patterned sensory inputs. In the cortical anlage of newborn mammals, neurons coassemble through electrical or chemical synapses either spontaneously or by activation of transmitter-gated receptors. The neuronal network and the cellular mechanisms underlying this cortical self-organization process during early development are not completely understood. Here we show in an intact in vitro preparation of the immature mouse cerebral cortex that neurons are functionally coupled in local clusters by means of propagating network oscillations in the beta frequency range. In the newborn mouse, this activity requires an intact subplate and is strongly synchronized within a cortical column by gap junctions. With the developmental disappearance of the subplate at the end of the first postnatal week, activation of NMDA (N-methyl-D-aspartate) receptors in the immature cortical network is essential to generate this columnar activity pattern. Our findings show that during a brief developmental period the cortical network switches from a subplate-driven, gap-junction-coupled syncytium to a synaptic network acting through NMDA receptors to generate synchronized oscillatory activity, which may function as an early functional template for the development of the cortical columnar architecture.     

Reverse replay of behavioural sequences in hippocampal place cells during the awake state

The hippocampus has long been known to be involved in spatial navigational learning in rodents, and in memory for events in rodents, primates and humans. A unifying property of both navigation and event memory is a requirement for dealing with temporally sequenced information. Reactivation of temporally sequenced memories for previous behavioural experiences has been reported in sleep in rats. Here we report that sequential replay occurs in the rat hippocampus during awake periods immediately after spatial experience. This replay has a unique form, in which recent episodes of spatial experience are replayed in a temporally reversed order. This replay is suggestive of a role in the evaluation of event sequences in the manner of reinforcement learning models. We propose that such replay might constitute a general mechanism of learning and memory.     

Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice

Internal brain states form key determinants for sensory perception, sensorimotor coordination and learning. A prominent reflection of different brain states in the mammalian central nervous system is the presence of distinct patterns of cortical synchrony, as revealed by extracellular recordings of the electroencephalogram, local field potential and action potentials. Such temporal correlations of cortical activity are thought to be fundamental mechanisms of neuronal computation. However, it is unknown how cortical synchrony is reflected in the intracellular membrane potential (V(m)) dynamics of behaving animals. Here we show, using dual whole-cell recordings from layer 2/3 primary somatosensory barrel cortex in behaving mice, that the V(m) of nearby neurons is highly correlated during quiet wakefulness. However, when the mouse is whisking, an internally generated state change reduces the V(m) correlation, resulting in a desynchronized local field potential and electroencephalogram. Action potential activity was sparse during both quiet wakefulness and active whisking. Single action potentials were driven by a large, brief and specific excitatory input that was not present in the V(m) of neighbouring cells. Action potential initiation occurs with a higher signal-to-noise ratio during active whisking than during quiet periods. Therefore, we show that an internal brain state dynamically regulates cortical membrane potential synchrony during behaviour and defines different modes of cortical processing.     

A new measure to characterize multifractality of sleep electroencephalogram

Traditional methods for nonlinear dy-namic analysis,such as correlation dimension,Lyapunov exponent,approximate entropy,detrended fluctuation analysis,using a single parameter,cannot fully describe the extremely sophisticated behavior of electroencephalogram (EEG). The multifractal for-malism reveals more “hidden” information of EEG by using singularity spectrum to characterize its nonlin-ear dynamics. In this paper,the zero-crossing time intervals of sleep EEG were studied using multifractal analysis. A new multifractal measure Δasα was pro-posed to describe the asymmetry of singularity spec-trum,and compared with the singularity strength range Δα that was normally used as a degree indi-cator of multifractality. One-way analysis of variance and multiple comparison tests showed that the new measure we proposed gave better discrimination of sleep stages,especially in the discrimination be-tween sleep and awake,and between sleep stages 3 and 4.     

一种改进的脑电癫痫波自动分析系统

脑电癫痫波的自动检测与分类是具有重要临床意义的课题。现存的算法大都着重于对棘、尖波形的检测 ,而忽略了慢波所包含的有用信息。为满足临床要求 ,论文提出了一种改进的脑电癫痫波自动分析系统。系统采用“分层次、多方法”的检测策略 ,兼顾了各种癫痫病理波形 ;整个处理过程综合应用了自适应预测、小波变换、人工神经网络、启发式规则等多种信号处理方法。经临床数据测试 ,该系统对癫痫波的总检测率达 83.6 % ,误检率为 1.1%。通过分层次处理 ,运用多方法的结合 ,可以提高检测敏感度和特异度 ,减少计算量 ,适合对长程脑电数据进行分析     

一种分析睡眠脑电图的时频特征图

使用Choi-Williams分布对一段睡眠脑电图（EEG）信号进行时频变换，利用局部频谱的特征估计各个时间间隔里的波形，并得到局部频谱的特征曲线，整段EEG信号中所有时间咪上的频谱特征曲线组成一种时频特征图，使用该时频特征图分析睡眠EEG，不仅能够统计该段EEG信号中各种基本波形的出现情况，而且可以观察EEG信号中每个基本波形的变化方式，通过时频特征图对采集的实际睡眠EEG数据进行分阶实验，结果表明，时频特征图可以作为一种分析睡眠EFG有效工具，有良好的应用前景。     

Dynamics of travelling waves in visual perception

Nonlinear wave propagation is ubiquitous in nature, appearing in chemical reaction kinetics, cardiac tissue dynamics, cortical spreading depression and slow wave sleep. The application of dynamical modelling has provided valuable insights into the mechanisms underlying such nonlinear wave phenomena in several domains. Wave propagation can also be perceived as sweeping waves of visibility that occur when the two eyes view radically different stimuli. Termed binocular rivalry, these fluctuating states of perceptual dominance and suppression are thought to provide a window into the neural dynamics that underlie conscious visual awareness. Here we introduce a technique to measure the speed of rivalry dominance waves propagating around a large, essentially one-dimensional annulus. When mapped onto visual cortex, propagation speed is independent of eccentricity. Propagation speed doubles when waves travel along continuous contours, thus demonstrating effects of collinear facilitation. A neural model with reciprocal inhibition between two layers of units provides a quantitative explanation of dominance wave propagation in terms of disinhibition. Dominance waves provide a new tool for investigating fundamental cortical dynamics.     

126例癫痫患儿临床与脑电图分析

目的：儿童癫痫占痫性发作患者中60%,做到早期诊断与合理治疗,能使80%痫性发作的患儿得到满意的控制,脑电图检测最敏感反映脑细胞功能状态的指标,对儿童癫痫早期诊断合理治疗及预后判定都有十分重要意义.方法：采用国产PRD-2000A型数字化脑电图定量分析仪,对126例临床痫性发作间歇期进行脑电图描记.结果：126例患儿正常23.8%,异常76.2%,其中痫性放电54%,慢波异常44例.结论：癫痫是大脑神经元群反复异常放电所致神经系统功能性疾病,而脑电图检查能较准确反应大脑功能状态,特别是发作性痫性放电的特征性改变,仍是临床对癫痫诊断的金标准.