Functions of the ON and OFF channels of the visual system

In the mammalian eye, the ON-centre and OFF-centre retinal ganglion cells form two major pathways projecting to central visual structures from the retina. These two pathways originate at the bipolar cell level: one class of bipolar cells becomes hyperpolarized in response to light, as do all photoreceptor cells, and the other class becomes depolarized on exposure to light, thereby inverting the receptor signal. It has recently become possible to examine the functional role of the ON-pathway in vision by selectively blocking it at the bipolar cell level using the glutamate neurotransmitter analogue 2-amino-4-phosphonobutyrate (APB)1. APB application to monkey, cat and rabbit retinas abolishes ON responses in retinal ganglion cells, the lateral geniculate nucleus and the visual cortex but has no effect on the centre-surround antagonism of OFF cells or the orientation and direction selectivities in the cortex2-5. These and related findings6-11 suggest that the ON and OFF pathways remain largely separate through the lateral geniculate nucleus and that in the cortex, contrary to some hypotheses, they are not directly involved in mechanisms giving rise to orientation and direction selectivities. We have examined the roles of the ON and OFF channels in vision in rhesus monkeys trained to do visual detection and discrimination tasks. We report here that the ON channel is reversibly blocked by injection of APB into the vitreous. Detection of light increment but not of light decrement is severely impaired, and there is a pronounced loss in contrast sensitivity. The perception of shape, colour, flicker, movement and stereo images is only mildly impaired, but longer times are required for their discrimination. Our results suggest that two reasons that the mammalian visual system has both ON and OFF channels is to yield equal sensitivity and rapid information transfer for both incremental and decremental light stimuli and to facilitate high contrast sensitivity.     

小脑经颅直流电刺激技术提升运动表现的应用

小脑是脑皮层下的一个重要运动调节中枢,它与大脑不同皮层区域在解剖和功能上紧密连接,配合大脑皮层完成机体的运动功能和运动学习。经颅直流电刺激(transcranial direct current stimulation, tDCS)是一种非侵入性的脑刺激技术,通过电极将微弱的电流作用于小脑能有效地提升皮层脊髓兴奋性和调控小脑与大脑皮层间的功能连接。本文系统梳理近20年国内外关于tDCS刺激小脑对提升人类运动表现影响的相关文献,研究结果表明tDCS刺激小脑可以改善人体的运动表现,如姿势控制、运动适应与运动学习、肌肉力量表现等。然而,tDCS刺激小脑的生理机制和刺激强度、刺激时间、刺激时间间隔等参数的选择有待进一步研究。未来的体育科学研究中,如何将tDCS刺激小脑的技术应用于运动训练,帮助运动员突破现有的运动能力仍有待深入探究。     

刺激大鼠杏仁外侧核对听皮层神经元调频声反应的影响

采用在体细胞外单细胞记录方法,研究电刺激杏仁外侧核对调频声所诱发的听皮层神经元反应的影响.实验在34只乌拉坦麻醉的SD大鼠上进行,在皮层41区记录了113个对调频声有反应的细胞电活动.观察发现,这些神经元对调频声刺激的反应可分为ON反应,OFF反应,ON-OFF反应,持续性反应和给声抑制反应几种类型.在观察对其中42个神经元的声反应时给予了杏仁外侧核电刺激,其中22%的神经元反应被易化,48%的神经元反应受到了抑制,另外30%神经元的声反应未受杏仁外侧核刺激的影响.这些影响进一步表明,杏仁复合体可在皮层水平参与听觉上传信息的处理,包括听觉信息的加工与整合.同时也表明杏仁核在上传听觉信息的筛选中可能具有重要的作用.     

基于极限环法的PID快速自整定的一种实现

探讨了基于极限环法的ＰＩＤ在线快速自整定理论和实现问题,提出采用满足度－零度继电特性生成极限环,并应用自振荡自适应理论和离散Ｆｏｕｒｉｅｒ级数变换滤波算法进行临界参数估计,还引入自适应预调点概念处理自整定的安全性问题。     

Early consolidation in human primary motor cortex.

Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation.     

帕金森病研究进展

 帕金森病（PD）是常见的神经系统变性疾病,典型的PD病理表现为脑中黑质多巴胺神经元退行性变和路易小体沉积,但这些改变不能完全解释PD产生的临床症状,目前PD的发病原因及机制尚不明确,尚未建立系统的早期诊断及保护治疗方式。随着诊断及治疗技术的提高,生物学标记物、脑网络及神经调控等有望为PD早期诊断、机制探索及个体化治疗提供基础。本文综述了PD在生物学标记物、脑网络研究及神经调控治疗领域的研究进展。     

Functional connectivity in the retina at the resolution of photoreceptors

To understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons.     

ON and OFF pathways in Drosophila motion vision

Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and circuits are still elusive. In the lamina, the first optic neuropile of Drosophila melanogaster, photoreceptor signals split into five parallel pathways, L1-L5. Here we examine how these pathways contribute to visual motion detection by combining genetic block and reconstitution of neural activity in different lamina cell types with whole-cell recordings from downstream motion-sensitive neurons. We find reduced responses to moving gratings if L1 or L2 is blocked; however, reconstitution of photoreceptor input to only L1 or L2 results in wild-type responses. Thus, the first experiment indicates the necessity of both pathways, whereas the second indicates sufficiency of each single pathway. This contradiction can be explained by electrical coupling between L1 and L2, allowing for activation of both pathways even when only one of them receives photoreceptor input. A fundamental difference between the L1 pathway and the L2 pathway is uncovered when blocking L1 or L2 output while presenting moving edges of positive (ON) or negative (OFF) contrast polarity: blocking L1 eliminates the response to moving ON edges, whereas blocking L2 eliminates the response to moving OFF edges. Thus, similar to the segregation of photoreceptor signals in ON and OFF bipolar cell pathways in the vertebrate retina, photoreceptor signals segregate into ON-L1 and OFF-L2 channels in the lamina of Drosophila.     

Bipolar cells in the mudpuppy retina use an excitatory amino acid neurotransmitter

The bipolar cells of the vertebrate retina are the principal neuronal elements which transmit photoreceptor activity from the outer to the inner retina. An important function of the bipolars is to segregate photoreceptor input into independent ON and OFF channels which are subserved, respectively, by the depolarizing and hyperpolarizing bipolar subtypes. Ultrastructural and physiological observations suggest that chemical neurotransmission is the predominant means of bipolar input to the inner retina. Both ON and OFF bipolars apparently release excitatory transmitters. Histological studies with cytotoxic agents and physiological studies indicate that third-order neurones have excitatory amino acid receptors. In ON-OFF amacrine and ganglion cells, which receive input from both bipolars, ON and OFF excitation have a similar ionic basis, suggesting that the same transmitter may be released by both types of bipolars. We have now found that (+/-)cis-2,3-piperidine dicarboxylic acid (PDA), a new excitatory amino acid antagonist, blocks bipolar input to the inner retina and thus suggests that an excitatory amino acid is a bipolar cell transmitter.     

Direct control of paralysed muscles by cortical neurons

A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury by artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralysed limbs. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms, and paralysed muscles have been activated by functional electrical stimulation. Here we show that Macaca nemestrina monkeys can directly control stimulation of muscles using the activity of neurons in the motor cortex, thereby restoring goal-directed movements to a transiently paralysed arm. Moreover, neurons could control functional stimulation equally well regardless of any previous association to movement, a finding that considerably expands the source of control signals for brain-machine interfaces. Monkeys learned to use these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron-muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralysed limbs.     

Identification of a distinct synaptic glutamate receptor on horizontal cells in mudpuppy retina

The separation of ON and OFF channels and the development of an antagonistic surround occur at the first synapse in the vertebrate retina. This functional differentiation is mediated by the action of the photoreceptor neurotransmitter on the ON bipolar, OFF bipolar and horizontal cells, respectively. Glutamate mimics the action of the photoreceptor transmitter on all second-order neurones in fish, amphibian and mammalian retinas. The diversity of cellular responses produced by one neurotransmitter raises the possibility of multiple postsynaptic receptor-ionophore complexes. We reported previously that one glutamate analogue, 2-amino-4-phosphonobutyrate, reveals that the ON bipolar synaptic receptor is pharmacologically different from those of other second-order neurones. The results presented here demonstrate that another glutamate analogue, D-O-phosphoserine, selectively antagonizes the synaptic responses of horizontal cells. Taken together, these findings indicate that there are three glutamate-like receptor subtypes in the outer retina and suggest a correlation between receptor subtype and the physiological properties of second-order neurones.     

Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex

Neuronal activity in the motor cortex is understood to be correlated with movements, but the impact of action potentials (APs) in single cortical neurons on the generation of movement has not been fully determined. Here we show that trains of APs in single pyramidal cells of rat motor cortex can evoke long sequences of small whisker movements. For layer-5 pyramids, we find that evoked rhythmic movements have a constant phase relative to the AP train, indicating that single layer-5 pyramids can reset the rhythm of whisker movements. Action potentials evoked in layer-6 pyramids can generate bursts of rhythmic whisking, with a variable phase of movements relative to the AP train. An increasing number of APs decreases the latency to onset of movement, whereas AP frequency determines movement direction and amplitude. We find that the efficacy of cortical APs in evoking whisker movements is not dependent on background cortical activity and is greatly enhanced in waking rats. We conclude that in vibrissae motor cortex sparse AP activity can evoke movements.     

Involvement of secondary motor areas in externally-triggered single-finger movements of dominant and non-dominant hands

Abstract Whether the secondary motor areas are involved in simple voluntary movements remains controversial. Differences in the neural substrates of movements with the dominant and the non-dominant hands have not been well documented. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the hemodynamic response in the primary motor cortex (M1), supple-mentary motor area (SMA) and premotor cortex (PMC) in six healthy right-handed subjects while performing a visually-guided finger-tapping task with their dominant or non-dominant hands. Significant activation was observed in M1, SMA and PMC during this externally triggered simple voluntary movement task. While dominant hand movements only activated contralateral motor areas, non-domi-nant hand movements also activated ipsilateral SMA and PMC. The results provide strong evidence for the involvement of the secondary motor areas in simple voluntarymovements, and also suggest that movements of the dominant hand primarily engage the contralateral secondary motor areas, whereas movements of the non-dominant hand engage bilateral secondary motor areas.     

Restoration of grasp following paralysis through brain-controlled stimulation of muscles

Patients with spinal cord injury lack the connections between brain and spinal cord circuits that are essential for voluntary movement. Clinical systems that achieve muscle contraction through functional electrical stimulation (FES) have proven to be effective in allowing patients with tetraplegia to regain control of hand movements and to achieve a greater measure of independence in daily activities. In existing clinical systems, the patient uses residual proximal limb movements to trigger pre-programmed stimulation that causes the paralysed muscles to contract, allowing use of one or two basic grasps. Instead, we have developed an FES system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain. We simulated some of the effects of the paralysis caused by C5 or C6 spinal cord injury by injecting rhesus monkeys with a local anaesthetic to block the median and ulnar nerves at the elbow. Then, using recordings from approximately 100 neurons in the motor cortex, we predicted the intended activity of several of the paralysed muscles, and used these predictions to control the intensity of stimulation of the same muscles. This process essentially bypassed the spinal cord, restoring to the monkeys voluntary control of their paralysed muscles. This achievement is a major advance towards similar restoration of hand function in human patients through brain-controlled FES. We anticipate that in human patients, this neuroprosthesis would allow much more flexible and dexterous use of the hand than is possible with existing FES systems.     

IP网络流量产生器的研究与实现

分析了造成IP网络流量自相似性的根本原因以及ON/OFF源汇聚程度对自相似度的影响.针对上述分析结论,实现了一个能够单点或分布式产生IP网络自相似业务量的产生器.实际环境中测试显示,该产生器能够较好地反应文件大小,协议类型,ON/OFF逗留时间以及源汇聚程度与自相似度之间的关系.     

模糊开-关控制器的结构分析及其在激光凝固疗法中的应用

提出了一种新颖的时变模糊控制器计算可变开-关信号序列从而达到控制输出要求。模糊开-关控制器在生物医学激光凝固疗法中能有效地解决组织加热的非线性时变特性和810nm二极管激光功率不可调的情况。该模糊控制器的结构被解析地分析并与PD控制器相联系。体外(In vitro)实验结果表明该模糊控制系统在组织温度控制中的优越性能。     

新型光学双稳器件及基本光学逻辑门

本文研究了一种用雪崩异质结光晶体管和半导体激光器组成的新型光学双稳器件，讨论了在稳态工作时该双稳器件的四种工作模式。当其工作在光学双稳态模式时，最小临界触发光功率小于 １０ｕＷ，高态输出光功率大于 １ｍＷ，高、低态输出光功率之比大于４ｄＢ。用该双稳器件实现了与、或、非、与非、或非五种基本光学逻辑功能。     

Firing patterns of motor units in normal rats

Skeletal muscles consist of motor units which may differ considerably in contractile properties and types of usage. Some units participate mainly in relatively rare, quick movements and contract rapidly and are easily fatigued (type FF); others contribute to the maintenance of posture and hence contract slowly and are fatigue-resistant (type S), while others are both fast and fatigue-resistant (type FR). Our understanding of motor control mechanisms and the dependence of contractile properties on usage would be enhanced if more quantitative information were available concerning the firing patterns of individual motor units during normal motor behaviour. Therefore, we have made continuous recordings for extended periods from single motor units in the fast extensor digitorum longus (edl) and the slow soleus (sol) muscle of freely moving adult rats. By counting the total number of discharges for each unit, and by determining the distributions of interspike intervals and the duration of the individual impulse trains, we have obtained information about firing rate, amount of use, modulation of muscle force and tonic and phasic behaviour for 16 motor units. We now report that these units fall into three classes apparently corresponding to type FF and FR in the edl muscle and type S in the soleus muscle.     

Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1

Parkinson's disease is a pervasive, ageing-related neurodegenerative disease the cardinal motor symptoms of which reflect the loss of a small group of neurons, the dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial oxidant stress is widely viewed as being responsible for this loss, but why these particular neurons should be stressed is a mystery. Here we show, using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable SNc dopaminergic neurons. The oxidant stress engaged defences that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D, which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ-1 (also known as PARK7 in humans and Park7 in mice), which is a gene associated with an early-onset form of Parkinson's disease, downregulated the expression of two uncoupling proteins (UCP4 (SLC25A27) and UCP5 (SLC25A14)), compromised calcium-induced uncoupling and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, these results point to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson's disease.     

直肠癌术中骶前静脉出血的止血治疗

目的:骶前静脉出血是直肠癌手术中严重的并发症,可危及病人的生命。本文讨论骶前静脉出血的原因及术中止血的临床经验。方法:从1985年1月~2004年12月共9例直肠癌患者于Miles术术中发生骶前静脉出血,术中分别采用环缝压迫止血法、图钉法及医用胶粘合法进行术中止血。结果:所有患者在术中均及时止血成功,顺利完成手术,术后未发生继发性出血。结论:为了避免骶前静脉出血的发生,关键在于手术时进入正确解剖层次、合理、细致、轻柔的手术操作。一旦发生出血,应尽快明确出血的部位,并根据不同的情况采用相应的措施。