Calcium and light adaptation in retinal rods and cones

Retinal rods and cones respond to light with a membrane hyperpolarization. This hyperpolarization is mediated by an ionic conductance (the light-regulated conductance) that is kept open in darkness by cyclic GMP acting as a ligand, and which closes in the light as a result of an increase in cGMP hydrolysis triggered by illumination. Calcium ions appear to have a role in this phototransduction process: they provide negative feedback between the conductance, which is permeable to Ca2+ (refs 4, 5), and the concentration of cGMP, which is sensitive to Ca2+ (refs 6-8). This feedback down-regulates the sensitivity to light of a photoreceptor and probably contributes to the important phenomenon of light adaptation in vision. It is still not clear, however, how much of the light adaptation is actually attributable to this Ca2+ feedback. We have examined the responses of amphibian rods and cones to light with the Ca2+ feedback removed. Normally, the response of a cell to a step of light rises transiently to a peak, but rapidly relaxes to a lower level, indicative of light adaptation. When the feedback is removed, however, the relaxation of the response is completely absent; furthermore, the steady response levels at different light-step intensities are well predicted by a statistical superposition of invariant single-photon responses. We therefore conclude that the Ca2+ feedback underlies essentially all light adaptation in rods and cones.     

Neuronal properties underlying processing of visual information in the barnacle.

Generation of a transient, amplified response to the dimming of light in the visual system of the barnacle involves two synaptic stages. It is accomplished primarily by decrementally conducting neurones that are similar to bipolar cells of the vertebrate retina.     

A presynaptic action of glutamate at the cone output synapse

Neurotransmitter release from many central nervous system synapses is regulated by 'autoreceptors' at the synaptic terminal, which bind the released transmitter and alter release accordingly. The photoreceptors of lower vertebrates are thought to use glutamate as a neurotransmitter. Glutamate conveys the visual signal to postsynaptic bipolar and horizontal cells, but has been reported not to act on the photoreceptors themselves. We show here that glutamate evokes a current, carried largely by chloride ions, in cones isolated from the tiger salamander retina. This response is localized to the synaptic terminal of the cone. Removing external sodium blocks this action of glutamate. These results suggest the existence of a positive feedback loop at the cone output synapse: over most of the light-response range, glutamate released by depolarization of the cone will cause further depolarization, increasing the gain of phototransduction. Glutamate released from rods may also polarize cones, modulating the gain of the cone output synapse. This system is surprisingly different from the autoreceptor systems for most other transmitters, which act in a negative feedback way.     

Temporal properties of pattern adaptation of relay cells in the lateral geniculate nucleus of cats

The temporal properties of pattern adaptation of relay cells induced by repeated sinusoidal drifting grating were investigated in the dorsal lateral geniculate nucleus (dLGN) of cats. The results showed that the response amplitude declined and the response latency prolonged when relay cells were pattern-adapted in dLGN, like the similar findings in visual cortex. However, in contrast to the result in cortex, the response phase of relay cells advanced. This implies that an inhibition with relatively long latency may participate in the pattern adaptation of dLGN cells and the adaptation in dLGN may be via a mechanism different from that of visual cortex.     

Motor learning in a recurrent network model based on the vestibulo-ocular reflex.

Most models of neural networks have assumed that neurons process information on a timescale of milliseconds and that the long-term modification of synaptic strengths underlies learning and memory. But neurons also have cellular mechanisms that operate on a timescale of tens or hundreds of milliseconds, such as a gradual rise in firing rate in response to injection of constant current or a rapid rise followed by a slower adaptation. These dynamic properties of neuronal responses are mediated by ion channels that are subject to modulation. We demonstrate here how a neural network with recurrent feedback connections can convert long-term modulation of neural responses that occur over these intermediate timescales into changes in the amplitude of the steady output from the system. This general principle may be relevant to many feedback systems in the brain. Here it is applied to the vestibulo-ocular reflex, whose amplitude is subject to long-term adaptive modification by visual inputs. The model reconciles apparently contradictory data on the neural locus of the cellular mechanisms that mediate this simple form of learning and memory.     

Light adaptation in cone vision involves switching between receptor and post-receptor sites

We see over an enormous range of mean light levels, greater than the range of output signals retinal neurons can produce. Even highlights and shadows within a single visual scene can differ approximately 10,000-fold in intensity-exceeding the range of distinct neural signals by a factor of approximately 100. The effectiveness of daylight vision under these conditions relies on at least two retinal mechanisms that adjust sensitivity in the approximately 200 ms intervals between saccades. One mechanism is in the cone photoreceptors (receptor adaptation) and the other is at a previously unknown location within the retinal circuitry that benefits from convergence of signals from multiple cones (post-receptor adaptation). Here we find that post-receptor adaptation occurs as signals are relayed from cone bipolar cells to ganglion cells. Furthermore, we find that the two adaptive mechanisms are essentially mutually exclusive: as light levels increase the main site of adaptation switches from the circuitry to the cones. These findings help explain how human cone vision encodes everyday scenes, and, more generally, how sensory systems handle the challenges posed by a diverse physical environment.     

Development of the light response in neonatal mammalian rods

The sensitivity to light is low in many neonatal mammals when compared with that in the adult. In human infants at one month of age, for example, the dark-adapted sensitivity for detection of large stimuli is 50 times lower than in the adult, and in rats the overall sensitivity of the neonatal retina is also low compared with the adult. This low sensitivity in the neonate has been attributed to a number of factors, but the possibility that the photoreceptors themselves might be an important limitation on the overall visual sensitivity has not so far been clearly established. Here we record the light response of single neonatal rat rods and find that the sensitivity is considerably lower than in the adult. The response to a single photoisomerization is normal in the neonate, and the sensitivity deficit can therefore be attributed to a low level of functional rhodopsin. Opsin, the protein component of rhodopsin, must be present in normal amounts, as the sensitivity can be restored to adult levels by treating the retina with 9-cis retinal, an active homologue of the native chromophore 11-cis retinal. The low sensitivity of photoreceptors in the neonate can therefore be attributed mainly to a low concentration of 11-cis retinal in the developing retina.     

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.     

Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice

In the mammalian retina, besides the conventional rod-cone system, a melanopsin-associated photoreceptive system exists that conveys photic information for accessory visual functions such as pupillary light reflex and circadian photo-entrainment. On ablation of the melanopsin gene, retinal ganglion cells that normally express melanopsin are no longer intrinsically photosensitive. Furthermore, pupil reflex, light-induced phase delays of the circadian clock and period lengthening of the circadian rhythm in constant light are all partially impaired. Here, we investigated whether additional photoreceptive systems participate in these responses. Using mice lacking rods and cones, we measured the action spectrum for phase-shifting the circadian rhythm of locomotor behaviour. This spectrum matches that for the pupillary light reflex in mice of the same genotype, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells. We have also generated mice lacking melanopsin coupled with disabled rod and cone phototransduction mechanisms. These animals have an intact retina but fail to show any significant pupil reflex, to entrain to light/dark cycles, and to show any masking response to light. Thus, the rod-cone and melanopsin systems together seem to provide all of the photic input for these accessory visual functions.     

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.     

游泳运动员赛前训练期生化指标的监测分析

为了解游泳运动员赛前训练的生化特点和身体机能的变化规律,对参加全国游泳冠军赛的15名运动员赛前训练期的部分生化指标进行了监测.结果发现:(1)优秀游泳运动员的Hb,RBC,HCT在赛前训练初期没有明显变化,训练中期明显下降,到训练后期逐步回升并且达到整个训练周期的最高水平.(2)血清CK在赛前训练中变化幅度较大,训练中期有明显的升高,在训练末期回落到较低水平;男、女运动员BU变化幅度不大并且均在正常范围之内.(3)T/C比值在训练初期明显降低,在训练末期回升到赛前水平.结论:这种负荷方式的赛前训练既达到了对机体形成刺激作用又能达到适应和恢复的目的.在训练末期优秀游泳运动员的血液携氧能力、营养状况、内分泌机能状态等均得到恢复和改善.     

Differences in the kinetics of rod and cone synaptic transmission

Photoreceptors of the vertebrate retina hyperpolarize in response to light. The hyperpolarization elicited by a brief flash is approximately ten times slower in rods than in cones of the same retina. We have examined the amplification and temporal properties of synaptic transfer of rod and cone signals to a common postsynaptic element, the horizontal cell. We find that the kinetics of signal transfer at these chemical synapses parallels the speed of the light-evoked signals themselves.     

Transformation from temporal to rate coding in a somatosensory thalamocortical pathway

The anatomical connections from the whiskers to the rodent somatosensory (barrel) cortex form two parallel (lemniscal and paralemniscal) pathways. It is unclear whether the paralemniscal pathway is directly involved in tactile processing, because paralemniscal neuronal responses show poor spatial resolution, labile latencies and strong dependence on cortical feedback. Here we show that the paralemniscal system can transform temporally encoded vibrissal information into a rate code. We recorded the representations of the frequency of whisker movement along the two pathways in anaesthetized rats. In response to varying stimulus frequencies, the lemniscal neurons exhibited amplitude modulations and constant latencies. In contrast, paralemniscal neurons in both thalamus and cortex coded the input frequency as changes in latency. Because the onset latencies increased and the offset latencies remained constant, the latency increments were translated into a rate code: increasing onset latencies led to lower spike counts. A thalamocortical loop that includes cortical oscillations and thalamic gating can account for these results. Thus, variable latencies and effective cortical feedback in the paralemniscal system can serve the processing of temporal sensory cues, such as those that encode object location during whisking. In contrast, fixed time locking in the lemniscal system is crucial for reliable spatial processing.     

Orientation-specific cortical responses develop in early infancy

Neurones in the visual cortex of higher mammals differ from those elsewhere in the visual pathway in that the majority respond selectively to particular edge or bar orientations in the stimulus. We have developed a visually evoked potential (VEP) technique which isolates the response of orientation-selective mechanisms from that of cortical or sub-cortical neurones which lack orientation selectivity. We are unable to find such orientation-selective responses in newborn human infants within the sensitivity of our method, but repeated longitudinal testing of individual infants shows that measurable responses emerge around 6 weeks of age. This result is consistent with the idea that human cortical visual function is very immature at birth, but develops rapidly in the first two postnatal months.     

A comparison of inhibition in orientation and spatial frequency selectivity of cat visual cortex

Neurones in the visual cortex are highly selective for orientation and spatial frequency of visual stimuli. There is strong neurophysiological evidence that orientation selectivity is enhanced by inhibitory interconnections between columns in the cortex which have different orientation sensitivities, an idea which is supported by experiments using neuropharmacological manipulation or complex visual stimuli. It has also been proposed that selectivity for spatial frequency is mediated in part by a similar mechanism to that for orientation, although evidence for this is based on special use of visual stimuli, which hampers interpretation of the findings. We have therefore examined selectivity for both orientation and spatial frequency using a technique which allows direct inferences about inhibitory processes. Our method uses microiontophoresis of an excitatory amino acid to elevate maintained discharge of single neurones in the visual cortex. We then present visual stimuli both within and outside the range of orientations and spatial frequencies which cause a cell to respond with increased discharge. Our results show that orientations presented on either side of the responsive range usually produce clear suppression of maintained discharge. In marked contrast, spatial frequencies shown to either side of the responsive range have little or no effect on maintained activity. We conclude that there is an intracortical organization of inhibitory connections between cells tuned to different orientations but not different spatial frequencies.     

Anticipation of moving stimuli by the retina

A flash of light evokes neural activity in the brain with a delay of 30-100 milliseconds, much of which is due to the slow process of visual transduction in photoreceptors. A moving object can cover a considerable distance in this time, and should therefore be seen noticeably behind its actual location. As this conflicts with everyday experience, it has been suggested that the visual cortex uses the delayed visual data from the eye to extrapolate the trajectory of a moving object, so that it is perceived at its actual location. Here we report that such anticipation of moving stimuli begins in the retina. A moving bar elicits a moving wave of spiking activity in the population of retinal ganglion cells. Rather than lagging behind the visual image, the population activity travels near the leading edge of the moving bar. This response is observed over a wide range of speeds and apparently compensates for the visual response latency. We show how this anticipation follows from known mechanisms of retinal processing.     

Effect of impulse blockage on cytochrome oxidase activity in monkey visual system

Cytochrome oxidase (cytochrome c oxidase; ferrocytochrome c: oxygen oxidoreductase, EC 1.9.2.1) has been introduced as an oxidative metabolic marker for neurones in the central nervous system. Previous studies have shown that mature neurones remained sensitive to altered functional demands, and that both developing and adult neurones responded to sensory deprivation or deafferentation by reducing their cytochrome oxidase (Cyt. Ox.) activity. More recently, we showed that the blockage of retinal impulse transmission with tetrodotoxin led to a reversible reduction in Cyt. Ox. staining of affected lateral geniculate (LGN) and striate neurones in adult cats. The present study sought to extend these findings to adult monkeys, where Cyt. Ox. 'puffs' or 'blobs' are uniquely present in the visual cortex. We found that, while the retina remained histologically intact, with only moderate decreases in Cyt. Ox. staining of large ganglion cells and the two plexiform layers, subtle changes occurred in the LGN as early as 1 day post-tetrodotoxin injection, and clear reduction in enzyme levels was evident in both the LGN and the visual cortex by 3 days. Changes became progressively more severe up to 4 weeks post-injection. Within area 17, alternating bands of high and low Cyt. Ox. staining occurred in lamina IV, with alternating rows of dark and lightly reactive puffs superimposed in exact register. Thus, the mature visual neurones in the primate remain extremely sensitive to the cessation of retinal impulse transmission, and plastic metabolic changes occur through several synapses along the sensory pathway.     

Gaze direction controls response gain in primary visual-cortex neurons

To localize objects in space, the brain needs to combine information about the position of the stimulus on the retinae with information about the location of the eyes in their orbits. Interaction between these two types of information occurs in several cortical areas, but the role of the primary visual cortex (area V1) in this process has remained unclear. Here we show that, for half the cells recorded in area V1 of behaving monkeys, the classically described visual responses are strongly modulated by gaze direction. Specifically, we find that selectivity for horizontal retinal disparity-the difference in the position of a stimulus on each retina which relates to relative object distance-and for stimulus orientation may be present at a given gaze direction, but be absent or poorly expressed at another direction. Shifts in preferred disparity also occurred in several neurons. These neural changes were most often present at the beginning of the visual response, suggesting a feedforward gain control by eye position signals. Cortical neural processes for encoding information about the three-dimensional position of a stimulus in space therefore start as early as area V1.     

Spectral sensitivity of human cone photoreceptors

The brain computes visual colour by analysing the relative excitations of three types of retinal cones. Each cone excitation is governed by a spectral sensitivity function which relates the amplitude of the neural response to wavelength at constant light intensity. The spectral sensitivities of human cones are not well characterized. We report measuring the sensitivities by recording electrical responses of human cones to stimuli of different wavelengths. Spectral sensitivities of 'green' and 'red' cones, determined over the entire visible region, show peaks near 530 and 560 nm respectively, and are remarkably similar to those of the old-world monkey Macaca fascicularis. They satisfactorily predict the photopic luminosity function, a measure of the sensitivity of cone-mediated human vision to light of different wavelengths. The kinetics of the light responses of human cones also appeared similar to those of macaque cones: the time to peak response to a dim flash was 50-100 ms and there was a characteristic undershoot during recovery.     

高速列车半主动悬挂系统的振动及主动控制

本文对两自由度高速列车半主动悬挂系统的垂向振动进行研究,考虑了二系悬挂中的刚度三次非线性。采用模态设解法、多尺度法得到了振动系统的二次近似解析解及振动系统的平均方程。振动系统的二阶模态振幅远远大于一阶模态的振幅,重点讨论了外激励频率趋近振动系统二阶模态频率时的振动控制情况。对线性系统的时滞反馈控制表明,存下一个最佳的反馈增益系数,无论时滞量如何取值,当反馈增益系数取得该值时,车体的振幅达到最小。对非线性时滞反馈控制,针对某一反馈增益系数,存在时滞的某些减振区间,当时滞量在该区间取值时能够抑制车体的振动。并且存在一些时滞的最佳值,车体的振幅达到最小。研究结果表明,能够利用时滞反馈控制改善悬挂系统的振动特性,达到抑制车体振动的目的。