Stimulation in the rat of a nerve fiber bundle by a short UV pulse from an excimer laser

A bundle of central nervous fibers was excited in the rat with a short pulse (40 ns) of UV light produced by an excimer laser. Evoked responses were recorded in the thalamic ventralis posterior nucleus after stimulation of the medial lemniscus or the cuneate bundle in the spinal cord. The effects of electrical and optical fiber applied UV stimulation were compared in both cases. At threshold, the latency for the UV light stimulation was slightly longer than for electrical stimulation. The excitation threshold was 0.9 J/cm², very close to the UV photoablation threshold (order of 1 J/cm²). The intermediary events mediating the light excitation are discussed.     

Modeling of light absorption in tissue during infrared neural stimulation

A Monte Carlo model has been developed to simulate light transport and absorption in neural tissue during infrared neural stimulation (INS). A range of fiber core sizes and numerical apertures are compared illustrating the advantages of using simulations when designing a light delivery system. A range of wavelengths, commonly used for INS, are also compared for stimulation of nerves in the cochlea, in terms of both the energy absorbed and the change in temperature due to a laser pulse. Modeling suggests that a fiber with core diameter of 200 μm and NA=0.22 is optimal for optical stimulation in the geometry used and that temperature rises in the spiral ganglion neurons are as low as 0.1°C. The results show a need for more careful experimentation to allow different proposed mechanisms of INS to be distinguished.     

Intensity dependence of auditory evoked potentials during light interference in migraine

Migraine patients show interictally a strong intensity dependence of auditory evoked cortical potentials (IDAP) and a lack of habituation of evoked potentials. Photic drive on high-frequency flash stimulation is another well-known interictal feature in migraineurs, associated with alpha-rhythm hyper-synchronisation. We compared therefore the influence of light stimulation on IDAP in healthy volunteers (HV) and migraine patients. A continuous flash stimulation was delivered during the recording of auditory evoked potentials at suprathreshold increasing stimulation intensities. IDAP was measured as the amplitude/stimulus intensity function (ASF) slope. In HV, the ASF slope decreased during flash stimulation, whereas, on average, there was no significant change in migraineurs. A closer analysis of migraineurs disclosed two subgroups of patients with no detectable clinical differences: one, the largest, in which the ASF slope was normal at baseline, but increased during light stimulation, the other with an increased ASF slope at rest and a decrease during light interference. Visual sensory overload is able to increase IDAP in the majority of migraineurs, which contrasts with HV. We hypothesise that this could be due to hyper-synchronisation of the alpha rhythm because of photic drive and possibly thalamo-cortical dysfunction. A minority of migraineurs have, like HV, an IDAP reduction during light interference. They are, however, characterised, unlike most HV, by a high IDAP at baseline. Besides underscoring the pathophysiological heterogeneity of migraine, these results suggest that light interference might improve the phenotyping of migraine patients who have a normal IDAP in the resting condition.     

Central core control of developmental plasticity in the kitten visual cortex: II. Electrical activation of mesencephalic and diencephalic projections

Summary Fifteen dark-reared, 4- to 5-week-old kittens were stimulated monocularly with patterned light while they were anesthetized and paralyzed. Six of these kittens were exposed to the light stimuli only, in four kittens the light stimuli were paired with electric stimulation of the mesencephalic reticular formation and in five kittens with electric activation of the medial thalamic nuclei. Throughout the conditioning period, the ocular dominance of neurons in the visual cortex was determined from evoked potentials that were elicited either with electric stimulation of the optic nerves or with phase reversing gratings of variable spatial frequencies. In two kittens, ocular dominance changes were assessed after the end of the conditioning period by analyzing single unit receptive fields. Monocular stimulation with patterned light induced a marked shift of ocular dominance toward the stimulated eye, when the light stimulus was paired with electric activation of either the mesencephalic reticular formation or of the medial thalamus. Moreover, a substantial fraction of cells acquired mature receptive fields. No such changes occurred with light or electric stimulation alone. It is concluded that central core projections which modulate cortical excitability gate experience-dependent modifications of connections in the kitten visual cortex.Part of this work was supported by a grant from the Deutsche Forschungsgemeinschaft SFB50, A14     

Light-induced depolarization of neurons using a modified Shaker K(+) channel and a molecular photoswitch

To trigger action potentials in neurons, most investigators use electrical or chemical stimulation. Here we describe an optical stimulation method based on semi-synthetic light-activated ion channels. These SPARK (synthetic photoisomerizable azobenzene-regulated K(+)) channels consist of a synthetic azobenzene-containing photoswitch and a genetically modified Shaker K(+) channel protein. SPARK channels with a wild-type selectivity filter elicit hyperpolarization and suppress action potential firing when activated by 390 nm light. A mutation in the pore converts the K(+)-selective Shaker channel into a nonselective cation channel. Activation of this modified channel with the same wavelength of light elicits depolarization of the membrane potential. Expression of these depolarizing SPARK channels in neurons allows light to rapidly and reversibly trigger action potential firing. Hence, hyper- and depolarizing SPARK channels provide a means for eliciting opposite effects on neurons in response to the same light stimulus.     

Microstimulation of V1 affects the detection of visual targets: manipulation of target contrast

Electrical microstimulation of the striate cortex (area V1) in monkeys delays the execution of saccadic eye movements generated to a visual target located in the receptive field of the stimulated neurons. We have argued that this effect is because of disruption of the visual signal transmitted along the geniculostriate pathway. The delivery of electrical stimulation to V1 evokes a punctate light or dark phosphene in human subjects. If electrical stimulation of V1 in monkeys evokes a light or dark phosphene, then one might expect that the delay effect might vary according to whether monkeys are required to detect a light or a dark visual target. For instance, if the stimulation is activating V1 elements coding for a light visual stimulus but not a dark visual stimulus then stimulation may delay saccades generated to a light target but not to a dark target. We tested this idea by having monkeys generate saccadic eye movements to light or dark visual targets immediately after the stimulation was delivered to V1. We found that the delay effect induced by stimulation varied with target contrast, but remained invariant to whether a bright or dark visual target was presented in the receptive field of the stimulated neurons. The significance of these results is discussed with regard to using monkeys to develop a visual prosthesis for the blind.     

Differences in nucleotide and base DNA excision repair observed during mitogenic stimulation of bovine lymphocytes

The bromodeoxyuridine density-shift technique was used to examine nucleotide and base DNA excision repair in quiescent and lectin stimulated bovine lymphocytes damaged with either ultraviolet light or dimethyl sulfate (DMS). Compared to a number of human cell lines, quiescent lymphocytes were less proficient in the repair of both types of damage. Repair replication was enhanced upon mitogenic stimulation, but both the amount and time course of the increase in repair depended upon the damaging agent used. A 2–3-fold increase in UV light induced repair replication occurred early during stimulation and subsided only gradually as stimulation proceeded. However, the profile of DMS induced repair increased 7-fold and then decreased, in parallel with measurements of lectin-stimulated DNA replication. Estimates of average repair patch sizes showed that quiescent lymphocytes produced smaller patches of 7 nucleotides in response to DMS damage while UV light irradiation resulted in repair patches 20 nucleotides. During stimulation, patch sizes appeared to increase to maximum values of 45 33 nucleotides in response to UV light and DMS, respectively, one day prior to the peak of DNA replication. These increases in patch size were followed by a gradual decrease towards unstimulated levels. However, the appearance of a DNA species of intermediate density in the gradient profiles made the interpretation of repair patch sizes in stimulated cells difficult. These results are discussed as evidence not only for differences in the mechanisms of nucleotide and base excision repair but also for changes in repair as the cell progresses through the cell cycle.     

Influence on frog retina of alternating magnetic fields with special reference to ganglion cell activity

The effects of extremely low frequency (e.l.f.) electromagnetic fields on basal systems were studied. Frog retinas were exposed to magnetic fields with frequencies and flux densities that have been shown to induce magnetophosphenes in volunteers. The electrical activity in the retina induced by the field was recorded from the ganglion cell layer with a microelectrode technique. A threshold value was obtained at approximately 20 mT, and a sensitivity maximum at 20 Hz. A significant prolongation (4 ms) of the latency from light stimulus to response in the ganglion cell layer was obtained, if the preparation was simultaneously and continuously exposed to a magnetic field. A study of the reaction of the ganglion cells to light and to magnetic fields showed that those cells which were on-cells during light stimulation became off-cells during magnetic stimulation andvice versa. The magnetic field response occurred within approximately 5 ms. while the light stimulus response occurred only after an average of approximately 85 ms. Addition of Na-aspartate or CoCl₂ extinguished simultaneously the response both to light and to magnetic field stimuli.     

低频光诱发脑电在浅睡期的样本熵复杂度分析

睡眠障碍患者通常表现为从浅睡期进入深睡期存在困难,分析浅睡期脑电波的变化对研究睡眠效率和睡眠质量至关重要。通过分析低频光刺激下睡眠过程中脑电波的复杂度值变化,研究人在浅睡期脑电波对光刺激的响应,进而探讨外部光刺激对睡眠过程中脑电波的影响。使用美国neuroscan型脑电图仪,采集10例志愿者的光刺激睡眠和正常睡眠的脑电数据。首先,利用时频分析,对睡眠过程中的脑电信号进行分期,获得浅睡期脑电信号;然后,使用小波包分解,获得该期脑电波的各频段分量（δ波、θ波、α波和纺锤波）;接着,采用样本熵算法,分别计算浅睡期脑电信号的复杂度以及各频段脑电波的复杂度;最后,对志愿者在光刺激（5 Hz）和正常睡眠下浅睡期脑电复杂度进行比较,研究光刺激对脑电复杂度的响应情况。结果显示：在低频光刺激下,浅睡期脑电波复杂度的均值为0514 15,明显低于正常睡眠复杂度的均值0589 23,在中央区和顶区有显著性差异（P<005）。研究表明,5 Hz光刺激可诱发浅睡期θ波的同步响应,增强脑电波的节律性,有助于更好地进入深度睡眠。     

一种简易的眨眼动作检测方法

目的：介绍一种简易的眨眼动作测量方法。方法：通过光敏三极管接收眼睛反射的红外光。经简单的信号放大滤过装置实现直观精确的眨眼反射动作观测。结果：用此法测定出单次强光脉冲刺激、角膜吹气刺激和机械刺激等条件下家兔眨眼反射的脉冲形态、高度和宽度。结论：该方法不必涉及对实验动物的手术处理。属无创探测;操作简单易行,在保持动物正常生理状态下即可得到比较精确、科学的结果。     

Studies on cortical field potentials recorded during learning processes of visually initiated hand movements in monkeys

Summary A monkey was trained to lift a lever by wrist extension in response to a light stimulus. During the learning process of the task over several months, field potentials related not only to the task performance but also to substitution and stimulation experiments were recorded with chronically implanted electrodes on the surface and at a depth of 2.5–3.0 mm in the prefrontal, premotor, motor and prestriate cortices. In the substitution experiment, an examiner lifted a lever for the monkey so that it was watching the light and rewarded without the hand movement. In the stimulation experiment, the same light stimulus was simply delivered to the monkey. In a naive monkey which lifted the lever independently of the stimulus, stimulus-locked potentials were evoked by the task experiment in those cortices except the motor cortex, but none was elicited by the substitution or stimulation experiment. In a welltrained monkey, the substitution and stimulation experiments induced almost the same potentials as those prior to the task movement in respective cortices except the motor cortex, in which the component of cerebellar-induced premovement potential was not observed during the substitution and stimulation experiments. At an intermediate stage of learning, the situation was intermediate between the naive and well-trained stages and most premovement potentials except those in the motor cortex were elicited by the substitution experiment in reduced sizes, but nothing by the stimulation experiment.The present study suggests that the neuronal circuits for the operantly conditioned movement are functionally organized and gradually consolidated in the learning process, and that the consolidation is made earlier for the circuit involving association and premotor cortices than the circuit including the motor cortex in the process. The circuit to the motor cortex via the cerebro-cerebellar interconnection is recruited only on the execution of movement.     

The parasympathetic secretory nerves of the lacrimal gland of the cat

1. Electrical stimulation of the brain stem of the anaesthetized cat induces a secretion from the lacrimal gland.2. The secretion is abolished either by Vidian nerve section or by the application of nicotine to the sphenopalatine ganglion.3. In contrast to stimulation of the peripheral end of the cut Vidian nerve, stimulation of the central end induces lacrimal secretion.4. A new pathway is proposed in the light of the experimental findings.     

Functional mapping of color processing by magnetic resonance imaging of responses to selective P- and M-pathway stimulation

Magnetic resonance imaging sensitized to activity-related changes in cerebral blood oxygenation was performed to map responses to selective stimulation of the parvo- and magnocellular visual pathways in calcarine and adjacent ventral occipital cortex of human subjects. In a repetitive stimulation protocol isoluminant chromatic or isochromatic luminance modulation was alternated with steady light of the same mean chromaticity and luminance as a reference condition. While no significant effects were observed for diffuse luminance modulation, two consistent cortical foci responded to isoluminant chromatic stimulation. A strong response was obtained in calcarine cortex at both 2 and 10 Hz, and even for selective S-cone stimulation. A second weaker colorsensitive response was seen bilaterally in the collateral sulcus. Thus, the data not only confirm color-sensitive activation in the collateral sulcus elicited in previous studies by selective cognitive tasks, but additionally demonstrate color-sensitive activation in primary visual cortex. With stimuli defined according to electrophysiological response properties of early visual processing stages, this study complements phenomenological or cognitive approaches in functional mapping of the human visual system.     

Stimulus frequency affects c-fos expression in the rat visual system

We have characterised the c-fos expression patterns in various centers of the visual pathway of adult rats monocularly stimulated either by continuous or flickering light at different frequencies. Results show different immunocytochemical patterns in all centers studied, the geniculate lateral complex (LGC), superior colliculus (SC) and primary visual cortex (Oc1), depending on the physical characteristics of the stimulus (blinking frequency and light wavelength). After stimulation of the left eye, the ipsilateral pathway presents a substantial density of immunoresponsive cells, which is greater than expected with respect to the number of fibers that project ipsilaterally from the retina to the LGC and the superficial layers of the SC. A surprisingly high positive immunoresponsiveness is obtained in all cases with coherent light stimulation in the red spectrum (634 nm).     

Intermittent contralateral and ipsilateral hemiretinal stimulation and its effect on the phasic stretch reflex

The effect of visual stimulation on the phasic stretch reflex, measured isometrically by way of EMG recordings, was investigated with normal human subjects. Three experimental treatments were applied, namely 3 flashes of light presented as hemiretinal contralateral stimulation prior to tendon taps; similar hemiretinal stimulation presented ipsilaterally; and no flashes of light as a control condition. The analysis of variance showed that the MAP means and standard deviations for both of the lights conditions were significantly greater than for the control condition. Eleven out of 12 subjects showed a larger reflex response to stimulation of the brain ipsilateral to the tendon stimulated. The findings are discussed in terms of visual projections differentially affecting alpha and gamma motoneurons.     

A role for the redox site in the modulation of the NMDA receptor by light

Light has been shown to modulate NMDA receptor function. In this study, we have performed experiments aimed at elucidating the putative site of action of light within the receptor structure. Whole-cell recordings were performed in Chinese hamster ovary cells expressing various combinations of NMDA receptor subunits. Although there was no apparent difference in the actions of light between wild-type NR1-NR2A and NR1-NR2B subunit configurations, the light enhancement of NMDA-induced currents was either completely abolished or substantially diminished in the redox site mutants NR1a (C744A, C798A)-NR2B and NR1a (C744A, C798A)-NR2A. Further studies demonstrated that chemical reduction of NR1a-NR2B NMDA receptors decreased its sensitivity to light. In addition, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES), used to irreversibly bind free sulfhydryl groups and inactivate the redox site, abolished the effects of light on wild-type receptors. In contrast, no free sulfhydryls were available for MTSES following light stimulation, suggesting that light itself could not reduce the redox modulatory site. Our results suggest that a functionally intact, oxidized redox site is necessary for light-induced potentiation. Hence, light and redox modulation of the NMDA receptor may share a common intramolecular pathway for altering the function of this ion channel.     

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array--insulated by an inert oxide--allows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.     

Human pupillary light reflex and reaction time at different intensity of light stimulation (a simple motor reaction to modify the human pupillogram).

The relations between the parameters of a pupillary light reflex and the reaction time to four intensities of light stimulation were studied in 13 normal volunteers (mean age 21.7 years). The consensual pupillary reactions to light were recorded at an infrared-reflecting pupillograph; the reaction time (RT) was recorded by a button pressed with the thumb. All subjects were tested at least twice in two blocks of trials: NO-RT-block, where only pupillograms (PGs) were recorded; and RT-block, where simple motor reactions were performed and recorded on a tape simultaneously with PGs. It was demonstrated that: (1) the intensity of light stimulation is a principal factor influencing the parameters of the human PG and is not a principal factor influencing the visuo-motor reaction time; and (2) A simple motor reaction exerts an inhibitory effect on the PG-amplitude and latency and on other PG-parameters. Some implications of probable mechanisms of the inhibitory influence of RT-processing on the PG-parameters are discussed.     

A simple device detecting onset time of taste stimulation

A simple piece of equipment is described for recording the accurate onset time of chemical stimulation applied to the tongue surface. The equipment consists of an infrared light emitting diode, a phototransistor for monitoring the stimulus onset, and solid state logic circuits for generating electric pulses at the moment of stimulus onset.