Hyperoxia modified activation-induced blood oxygenation level-dependent response of human visual cortex (V1): an event-related functional magnetic resonance imaging study

To investigate the effect that hyperoxia has on the blood oxygenation level-dependent (BOLD) response to visual stimulation of human V1, an event-related functional magnetic resonance imaging technique was applied. The event-related paradigm consisted of 2 s of stimulation by a checkerboard reversing at a frequency of 8 Hz, followed by 18 s of control scans. The peak height and peak time of the BOLD response curves were compared under normoxic and hyperoxic conditions. It was found that the peak height was larger and the peak time shorter for hyperoxia than for normoxia. These results suggest that hyperoxia modified the activation-induced hemodynamic response of human V1.     

Light stimulus frequency dependence of activity in the rat visual system as studied with high-resolution BOLD fMRI

The neurophysiology of the rodent visual system has mainly been investigated by invasive and ex-vivo techniques providing fragmented data. This area of research has been deprived of functional MRI studies based on blood oxygenation level dependent (BOLD) contrast, which allows a whole brain approach with a high spatial and temporal resolution. In the present study, we looked at the neurovascular response properties of the visual system of the pigmented rat, focusing on the visual cortex (VC), the superior colliculus (SC) and the flocculus-paraflocculus of the cerebellum (FL-PFL), using BOLD fMRI under domitor anesthesia. Visual stimulation was performed monocularly or binocularly while flashing light from a strobe unit was presented. For each structure, we assessed the flashing frequency that evoked the optimal BOLD response: Neither the VC nor the FL-PFL displayed frequency dependence during monocular visual stimulation, but were most sensitive to low frequencies (1-5 Hz) when flashing light was provided binocularly. The SC responded optimally to high flashing rates (8-12 Hz) during both monocular and binocular stimulation. The signal intensity changes in the VC and FL-PFL were locked to the stimulation period, whereas the BOLD response in the SC showed a similar onset but a very slow recovery at offset. The VC and FL-PFL, but not the SC, showed signs of binocular competition. The observed correlation between frequency-dependent responses of different visual areas during binocular visual presentation suggests a functional relationship between the VC and FL-PFL rather than between the SC and FL-PFL.     

Stimulus frequency dependence of blood oxygenation level-dependent functional magnetic resonance imaging signals in the somatosensory cortex of rats

Understanding the mechanism of coupling between neuronal events and hemodynamic responses is important in non-invasive functional imaging of the brain. The stimulus frequency dependence of hemodynamic responses has been studied using a rat somatosensory cortex model; most results for short stimulus durations reveal peak frequencies at which the hemodynamic response is maximized. However, such peak frequencies have not been observed in studies using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals with long stimulus durations. To clarify whether the stimulus frequency dependence of BOLD signals depends on the stimulus duration, we measured BOLD signals at 7 T with short- and long-stimulus durations for stimulating rat forepaw at 1-10 Hz using spin-echo echo-planar imaging to enhance changes in activation focus. For both these durations, BOLD signals were significantly higher at stimulus frequencies of 3 or 5 Hz in agreement with the results of previous studies using optical techniques. Our results show that stimulus duration has little influence on the stimulus frequency dependence of BOLD signals in the rat somatosensory model. The discrepant results of most previous fMRI studies using gradient-echo sequence may be ascribed to the difference of imaging to enhance activation focus or draining vein.     

稳态视觉诱发电位频率响应特性研究

目的稳态视觉诱发电位(steady-state visual evoked potential,SSVEP)是大脑对周期性视觉刺激产生的响应,已广泛应用于基于脑电(electroencephalogram,EEG)的脑-机接口(brain-computer interface,BCI)。SSVEP频率响应曲线通常是以发光二极管(light emitting diode,LED)作为视觉刺激器的方式获得的。近年来,计算机显示器广泛用于产生闪烁刺激,然而基于计算机显示器的SSVEP频率响应曲线少有研究。为此,本文研究了基于计算机显示器的SSVEP频率响应特性。方法利用采样正弦编码方法在普通LCD显示器上产生了42个刺激频率(频率范围4~45 Hz),并收集了10位健康受试者的脑电数据,以研究SSVEP幅值/信噪比(signal-to-noise ratio,SNR)与刺激频率的关系。结果较强SSVEP响应出现在大脑枕区。SSVEP基频幅值的峰值出现在10 Hz处,且第二峰值出现在20 Hz处。SSVEP二次谐波幅值的峰值出现在6 Hz且在高刺激频率处幅值较小。低、中频段的SSVEP基频信噪比处于相当的水平。结论本文的实验结果可以为基于计算机显示器的SSVEP-BCIs的频率选择提供依据。     

Tuning of the ocular vestibular evoked myogenic potential (oVEMP) to AC sound shows two separate peaks

The ocular vestibular evoked myogenic potential (oVEMP) is a relatively new method used to assess otolith-ocular pathways in humans. When elicited using air-conducted (AC) sound stimulation, the oVEMP is thought to reflect mostly saccular activation. However, it has been recently suggested that utricular afferents may also contribute to the AC evoked oVEMP. While previous frequency tuning studies of the AC evoked oVEMP report predominately high frequency sensitivity (>400 Hz), few have included the lower frequencies (<200 Hz) at which it has been proposed the utricle is most sensitive. In this study, ten normal subjects were stimulated with AC sound delivered unilaterally using headphones over frequencies from 50 to 1,200 Hz at a near constant A-weighted intensity of 120 dB peak sound pressure level. For AC stimulation, the oVEMP demonstrated maximum amplitudes around 600 Hz, with a second, smaller peak occurring around 100 Hz. The AC evoked oVEMP tuning has two peaks, a dominant one consistent with excitation of the saccule and a smaller one consistent with excitation of the utricle.     

Stimulus frequency dependence of the linear relationship between local cerebral blood flow and field potential evoked by activation of rat somatosensory cortex

We investigated the relationship between evoked local cerebral blood flow (LCBF) and the field potential induced by somatosensory activation. The specific aim of the present study was to examine the correlation between variations of evoked LCBF and field potential when the stimulus duration was changed, and the dependency of the correlation on stimulus frequency. Evoked LCBF was measured using laser-Doppler flowmetry and the field potential was observed using a tungsten electrode inserted into the cortex alpha-chloralose-anesthetized rats. The cortex was activated by electrical stimulation of the hind paw with a 1.5 mA pulse (0.1 ms) applied at frequencies of 0.5, 1, 5 and 10 Hz for durations of 2, 5, 8, 10 or 15s. We extended our previous finding [Neurosci. Res. 40 (2001) 281-290], that both the magnitude of evoked LCBF (integrated LCBF) and the summed field potential (SigmaFP) exhibited a maximum at a stimulus frequency of 5 Hz to five different stimulus durations. Moreover, although variations of integrated LCBF and SigmaFP induced by changes in the stimulus duration were linearly correlated, the slope of the regression line depended on the stimulus frequency. This stimulus frequency dependence of the integrated LCBF-SigmaFP linear relationship may be because the vessel response is frequency dependent.     

Carbachol effects on hippocampal neurons in vitro: dependence on the rate of rise of carbachol tissue concentration

Summary Extracellular activity from vestibular nuclei neurons and vertical eye movements were recorded in the alert cat during sinusoidal optokinetic stimulation in the vertical plane at frequencies varying from 0.0125 Hz to 0.75 Hz. Among a population of 96 vestibular units located in and around Deiters' nucleus, 73 neurons (76%) displayed a firing rate modulation which followed the input at the standard parameters of visual stimulation (0.05 Hz; 10.1 deg/s or 9.1 cm/s peak to peak velocity). Two different patterns of modulation were found. In 42 cells (57%) an increase in the firing rate was observed during motion of the visual scene in the downward direction, while 31 neurons (43%) showed the opposite behavior, with an enhanced firing rate during upward movement. The phase of the neuronal responses was close (± 45°) to the velocity peaks (+90°: downward and -90°: upward) of visual scene motion for 65 among the 73 neurons. Mean values of phase was-6.1 ± 19.5° (SD) and -3.2 ± 15.5° (SD) with respect to the +90° and -90° velocity peaks, respectively. In the frequency range 0.0125–0.75 Hz, the phase of the neuronal responses remained almost stable, with only a slight lag which reaches -22° at the 0.25 Hz visual stimulation. The firing rate modulation was found to be predominant at low frequencies (0.0125 Hz–0.25 Hz), with three distinct peaks of modulation occurring either at 0.025 Hz, 0.10 Hz or 0.25 Hz, depending on the recorded cells. Above 0.5 Hz, the cell modulation was very poorly developed or even absent. A gain attenuation was observed in all units, which was more important in cells showing a peak of modulation at 0.025 Hz as compared with the others (-20.7 dB vs -9.6 dB, respectively, in the 0.025 Hz–0.25 Hz decade). The gain of the optokinetic reflex (OKR) progressively decreased from mean values of 0.78 ± 0.15 to 0.05 ± 0.06 in the 0.025 Hz–0.5 Hz frequency range. A close correlation was observed between the OKR slow phase velocity and the modulation of the neuronal responses in the two cell populations with maximal modulations at 0.10 Hz or 0.25 Hz. No correlations were noticed in the third population characterized by a peak of modulation at 0.025 Hz. In all units, the phase of eye movement velocity and of neuronal responses were both related to the velocity of the visual surround motion. These correlations were also found when varying the amplitude of the visual stimulation at a fixed frequency. Saturation was observed in the unit responses at velocities above 68.5°/s. When considering both the gain attenuation in the frequency range and the correlation between firing rate modulation and OKR slow phase velocity, two rather different cell populations can be distinguished: one with neurons peaking at 0.025 Hz (strong gain attenuation; no correlation with OKR velocity) and one with neurons peaking at 0.10 Hz or 0.25 Hz (slight gain attenuation; correlation with OKR velocity). This study points to the influence of visual motion cues on vestibular nuclei unit activity in the low-frequency range. A velocity coding of visual — surround motion in the vertical plane is performed by vestibular neurons. Our results in the alert cat suggest that both retinal (retinal slip) and extraretinal (proprioceptive afferences from eye muscles, efference copy) inputs can be involved in this visually induced modulation of vestibular nuclei neurons.     

Stimulation of the rat somatosensory cortex at different frequencies and pulse widths

Functional MRI (fMRI) during electrical somatosensory stimulation of the rat forepaw is a widely used model to investigate the functional organization of the somatosensory cortex or to study the underlying mechanisms of the blood oxygen level-dependent (BOLD) response. In reality, somatosensory stimuli have complex timing relationships and are of long duration. However, by default electrical sensory stimulation seems to be performed at an extremely short pulse width (0.3 ms). As the pulse duration may alter the neuronal response, our aim was to investigate the influence of a much longer stimulus pulse width (10 ms) using BOLD fMRI during electrical forepaw stimulation. The optimal neuronal response was investigated by varying the stimulus frequency at a fixed pulse duration (10 ms) and amplitude (1 mA). In a parallel experiment we measured the neuronal response directly by recording the somatosensory evoked potentials (SEPs). Quantification of the BOLD data revealed a shift in the optimal response frequencies to 8-10 Hz compared with 1 Hz at 0.3 ms. The amplitude of the recorded SEPs decreased with increasing stimulation frequency and did not display any correlation with the BOLD data. Nevertheless, the summated SEPs, which are a measure of the integrated neuronal activity as a function of time, displayed a similar response profile, with a similar maximum as observed by relative BOLD changes. This shift in optimal excitation frequencies might be related to the fact that an increased pulse width of an electrical stimulus alters the nature of the stimulation, generating also sensorimotor instead of merely somatosensory input. This may influence or alter the activated pathways, resulting in a shift in the optimal response profile.     

Steady-State Visual Evoked Potentials: Distributed Local Sources and Wave-Like Dynamics Are Sensitive to Flicker Frequency

Summary: Steady-state visual evoked potentials (SSVEPs) are used in cognitive and clinical studies of brain function because of excellent signal-to-noise ratios and relative immunity to artifacts. SSVEPs also provide a means to characterize preferred frequencies of neocortical dynamic processes. In this study, SSVEPs were recorded with 110 electrodes while subjects viewed random dot patterns flickered between 3 and 30 Hz. Peaks in SSVEP power were observed at delta (3 Hz), lower alpha (7 and 8 Hz), and upper alpha band (12 and 13 Hz) frequencies; the spatial distribution of SSVEP power is also strongly dependent on the input frequency suggesting cortical resonances. We characterized the cortical sources that generate SSVEPs at different input frequencies by applying surface Laplacians and spatial spectral analysis. Laplacian SSVEPs recorded are sensitive to small changes (1–2 Hz) in the input frequency at occipital and parietal electrodes indicating distinct local sources. At 10 Hz, local source activity occurs in multiple cortical regions; Laplacian SSVEPs are also observed in lateral frontal electrodes. Laplacian SSVEPs are negligible at many frontal electrodes that elicit strong potential SSVEPs at delta, lower alpha, and upper alpha bands. One-dimensional (anterior-posterior) spatial spectra indicate that distinct large-scale source distributions contribute SSVEP power in these frequency bands. In the upper alpha band, spatial spectra indicate the presence of long-wavelength (> 15 cm) traveling waves propagating from occipital to prefrontal electrodes. In the delta and lower alpha band, spatial spectra indicate that long-wavelength source distributions over posterior and anterior regions form standing-wave patterns. These results suggest that the SSVEP is generated by both (relatively stationary) localized sources and distributed sources that exhibit characteristics of wave phenomena. This research was supported by NIMH grant R01-68004.     

Human EEG responses to 1–100 Hz flicker: resonance phenomena in visual cortex and their potential correlation to cognitive phenomena

The individual properties of visual objects, like form or color, are represented in different areas in our visual cortex. In order to perceive one coherent object, its features have to be bound together. This was found to be achieved in cat and monkey brains by temporal correlation of the firing rates of neurons which code the same object. This firing rate is predominantly observed in the gamma frequency range (approx. 30–80 Hz, mainly around 40 Hz). In addition, it has been shown in humans that stimuli which flicker at gamma frequencies are processed faster by our brains than when they flicker at different frequencies. These effects could be due to neural oscillators, which preferably oscillate at certain frequencies, so-called resonance frequencies. It is also known that neurons in visual cortex respond to flickering stimuli at the frequency of the flickering light. If neural oscillators exist with resonance frequencies, they should respond more strongly to stimulation with their resonance frequency. We performed an experiment, where ten human subjects were presented flickering light at frequencies from 1 to 100 Hz in 1-Hz steps. The event-related potentials exhibited steady-state oscillations at all frequencies up to at least 90 Hz. Interestingly, the steady-state potentials exhibited clear resonance phenomena around 10, 20, 40 and 80 Hz. This could be a potential neural basis for gamma oscillations in binding experiments. The pattern of results resembles that of multiunit activity and local field potentials in cat visual cortex. Electronic Publication     

Frequency-dependent tactile responses in rat brain measured by functional MRI

We measured frequency-dependent functional MRI (fMRI) activations (at 11.7 T) in the somatosensory cortex with whisker and forepaw stimuli in the same alpha-chloralose anesthetized rats. Whisker and forepaw stimuli were attained by computer-controlled pulses of air puffs and electrical currents, respectively. Air puffs deflected (+/-2 mm) the chosen whisker(s) in the right snout in the rostral to caudal direction, and electrical currents (2 mA amplitude, 0.3 ms duration) stimulated the left forepaw with subcutaneous copper electrodes placed between the second and fourth digits. In the same subject, unimodal stimulation of whisker and forepaw gave rise to significant blood oxygen level-dependent (BOLD) signal increases in corresponding contralateral somatosensory areas of whisker barrel field (S1BF) and forelimb (S1FL), respectively, with no significant spatial overlap between these regions. The BOLD responses in S1(BF) and S1(FL) regions were found to be differentially variable with frequency of each stimulus type. In the S1BF, a linear increase in the BOLD response was observed with whisker stimulation frequency of up to approximately 12 Hz, beyond which the response seemed to saturate (and/or slightly attenuate) up to the maximum frequency studied (i.e. 30 Hz). In the S1FL, the magnitude of the BOLD response was largest at forepaw stimulation frequency between 1.5 and 3 Hz, beyond which the response diminished with little or no activity at frequencies higher than 20 Hz. The volume of tissue activated by each stimulus type followed a similar pattern to that of the stimulation frequency dependence. These results of bimodal whisker and forepaw stimuli in the same subject may provide a framework to study interactions of different tactile modules, with both fMRI and neurophysiology (i.e. inside and outside the magnet).     

Electrical and mechanical properties of the Crustacean stretch receptor during Sinusoidal length changes

Isolated slowly adapting stretch receptors of the crayfish (Astacus fluviatilis) were exposed to sinusoidal length changes. The mechanical force, the receptor current and the receptor potential were analysed in terms of frequency response (Bode plots) and input/output functions. Within the frequency range investigated (0.3 to 80 Hz) the mechanical force was found to be only slightly dependent on the frequency of the sinusoidal stimuli, the slope of the gain function in the Bode plot being close to zero. Dynamic length-force curves exhibited a characteristic hysteresis. In potential clamp experiments, the receptor current induced by sinusoidal length changes was dependent on the clamp potential attaining maximal amplitude at a membrane potential of about -20 to -30 mV for 80 Hz mechanical stimulation. The membrane potential at which the receptor current changed sign (the reversal potential) increased with increasing frequency. In Bode plots of the receptor current the gain was represented by a straight line, having a slope of about 1.2 dB/octave. The phase shift was positive at low frequencies. Bode plots of the receptor potential gain exhibited a characteristic peak in the region of 15 Hz. Below this peak the gain increased with about 1.2 dB/oct, above the peak the gain decreased with about 4.8 dB/oct. There was a small positive phase shift at low frequencies; at high frequencies the phase shift became negative. The impedance of the cell, as calculated from the receptor potentials and the current responses at resting membrane potential, gave Bode plots comparable to a simple resistive-capacitive filter compatible with the electrical properties of the receptor cell membrane. The cut-off frequency of this low pass filter decreased with decreasing stretch amplitude. One physiological significance of this finding, is that the performance of the receptor is improved at low levels of stimulation by reducing the bandwidth of the system.     

Hazardous nature of high-temporal-frequency strobe light stimulation: neural mechanisms revealed by magnetoencephalography

Individuals in contemporary society are continually exposed to various visual stimuli. Such stimulation, especially when high in temporal frequency, may sometimes cause unexpected events such as photosensitive seizures. Although many studies have demonstrated that high-temporal-frequency (>3 Hz) visual stimulation can yield hazardous responses in the CNS, the mechanisms by which it does so are still unclear. We therefore investigated the mechanisms of neural perturbation by high-temporal-frequency strobe light stimulation with high-temporal-frequency resolution (4–20 Hz with an interval of 2 Hz) using magnetoencephalography with high temporal and spatial resolution. We show that (1) three temporal dipole phases (phases 1, 2 and 3, by time course) can be identified in the visual evoked magnetic fields (VEF's) across stimulation frequencies based on the goodness-of-fit values for equivalent current dipole estimation and horizontal dipole directions, (2) the dipole moment of VEF's is correlated with autonomic nervous system activity in phases 1 and 2, (3) some temporal stimulation frequencies enhance magnetic responses in phases 1, 2 and 3, and (4) these frequencies are harmonically related, with a greatest common divisor frequency (fundamental frequency) of approximately 6.5 Hz. Our clarification of the temporal frequency characteristics of VEF's will contribute to understanding of the potential hazardous effects of high-temporal-frequency strobe light stimulation in the CNS.     

Blood oxygenation level-dependent (BOLD) functional MRI of visual stimulation in the rat retina at 11.7 T

Although optically based imaging techniques provide valuable functional and physiological information of the retina, they are mostly limited to the probing of the retinal surface and require an unobstructed light path. MRI, in contrast, could offer physiological and functional data without depth limitation. Blood oxygenation level-dependent functional MRI (BOLD fMRI) of the thin rat retina is, however, challenging because of the need for high spatial resolution, and the potential presence of eye movement and susceptibility artifacts. This study reports a novel application of high-resolution (111 × 111 × 1000 μm(3)) BOLD fMRI of visual stimulation in the anesthetized rat retina at 11.7 T. A high-field MRI scanner was utilized to improve the signal-to-noise ratio, spatial resolution and BOLD sensitivity. Visual stimuli (8 Hz diffuse achromatic light) robustly increased BOLD responses in the retina [5.0 ± 0.8% from activated pixels and 3.1 ± 1.1% from the whole-retina region of interest (mean ± SD), n = 12 trials on six rats, p < 0.05 compared with baseline]. Some activated pixels were detected surrounding the pupil and ciliary muscle because of accommodation reflex to visual stimuli, and were reduced with atropine and phenylephrine eye drops. BOLD fMRI scans without visual stimulations showed no significantly activated pixels (whole-retina BOLD changes were 0.08 ± 0.34%, n = 6 trials on five rats, not statistically different from baseline, p > 0.05). BOLD fMRI of visual stimulation has the potential to provide clinically relevant data to probe hemodynamic neurovascular coupling and dysfunction of the retina with depth resolution.     

Coupling Between Resting Cerebral Perfusion and EEG

While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21–48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2–4 Hz and theta: 4–7 Hz), middle (alpha: 8–13 Hz), and high (beta: 13–30 Hz and gamma: 30–45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.     

Frequency dependent effects of subthalamic nucleus stimulation in Parkinson's disease

Excessive synchronisation of basal ganglia activity at frequencies < 30 Hz is a hallmark of the parkinsonian state, and may contribute to bradykinesia. Accordingly, we electrically stimulated chronically implanted subthalamic macroelectrodes in 10 Parkinson's disease patients, after overnight withdrawal of anti-parkinsonian medication. We compared the effects of stimulation at 0, 5, 10, 15, 20, 25, 30, and ca. 130 Hz by measuring kinesia time (KT) in a tapping task. Although the effects of direct stimulation were small, frequency-response curves demonstrated local peaks at 5-10 Hz and at 20-25 Hz, superimposed upon an overall tendency for KT to reduce with increasing stimulation frequency. This is consistent with the hypothesis that spontaneous activities in these bands might promote bradykinesia.     

Induction of long-term potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex.

1. Intracellular recording was made from layer II-III cells in slice preparations of kitten (30-40 days old) visual cortex. Low-frequency (0.1 Hz) stimulation of white matter (WM) usually evoked an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). The postsynaptic potentials (PSPs) showed strong dependence on stimulus frequency. Early component of EPSP and IPSP evoked by weak stimulation both decreased monotonically at frequencies greater than 0.5-1 Hz. Strong stimulation similarly depressed the early EPSP at higher frequencies (greater than 2 Hz) and replaced the IPSP with a late EPSP, which had a maximum amplitude in the stimulus frequency range of 2-5 Hz. 2. Very weak WM stimulation sometimes evoked EPSPs in isolation from IPSPs. The falling phase of the EPSP revealed voltage dependence characteristic to the responses mediated by N-methyl-D-aspartate (NMDA) receptors and was depressed by application of an NMDA antagonist DL-2-amino-5-phosphonovalerate (APV), whereas the rising phase of the EPSP was insensitive to APV. 3. The early EPSPs followed by IPSPs were insensitive to APV but were replaced with a slow depolarizing potential by application of a non-NMDA antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX), indicating that the early EPSP is mediated by non-NMDA receptors. The slow depolarization was mediated by NMDA receptors because it was depressed by membrane hyperpolarization or addition of APV. 4. The late EPSP evoked by higher-frequency stimulation was abolished by APV, indicating that it is mediated by NMDA receptors, which are located either on the recorded cell or on presynaptic cells to the recorded cells. 5. Long-term potentiation (LTP) of EPSPs was examined in cells perfused with solutions containing 1 microM bicuculline methiodide (BIM), a gamma-aminobutyric acid (GABA) antagonist. WM was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes were tested by low-frequency (0.1 Hz) stimulation of WM. 6. LTP of early EPSPs occurred in more than one-half of the cells (8/13) after strong conditioning stimulation. The rising slope of the EPSP was increased 1.6 times on average. 7. To test involvement of NMDA receptors in the induction of LTP in the early EPSP, the effect of conditioning stimulation was studied in a solution containing 100 microM APV, which was sufficient to block completely synaptic transmission mediated by NMDA receptors. LTP occurred in the same frequency and magnitude as in control solution.     

Transmission from vasoconstrictor and vasodilator nerves to single smooth muscle cells of the guinea-pig uterine artery

1. Previous studies have shown that perivascular nerve stimulation of the uterine artery of the guinea-pig evokes an adrenergic constrictor response and a dilator response with two components. The first of these, only present during pregnancy, is cholinergic. The second is non-cholinergic and is present at all times. Intracellular recording from single smooth muscle cells in isolated arterial segments has now been used to investigate the transmission processes associated with these responses.2. The mean resting membrane potential of the muscle cells was 60.7 mV in arteries from both virgin animals (range 50-68 mV) and from animals in late pregnancy (range 48-76 mV).3. Low frequency perivascular stimulation evoked excitatory junction potentials (EJPs) which reached a maximum amplitude of about 5 mV, lasted about 900-1000 msec, and showed facilitation at frequencies of stimulation of 0.1 Hz or above and summation at frequencies of stimulation of 1.2 Hz or above.4. These EJPs were abolished by exposure of the tissue to bretylium (2 x 10(-6) g/ml.). It is therefore concluded that the EJPs were due to transmission from adrenergic nerves.5. Perivascular stimulation at frequencies above 10 Hz evoked a depolarizing response which was often surmounted by a small (5 mV) local spike potential. Such depolarizing responses were associated only with localized contractions of the arterial muscle.6. In the presence of low extracellular K(+) concentrations, perivascular stimulation at frequencies above 10 Hz gave rise to a depolarizing response topped by an action potential of up to 50 mV amplitude, and more generalized contraction of the tissue than was seen in normal K(+) solution.7. After blockade of the adrenergic vasoconstrictor fibres, no response to perivascular stimulation was observed normally. However, following moderate depolarization of the membrane with noradrenaline, stimulation evoked a hyperpolarization of up to 6 mV in amplitude.8. This response showed no discrete junction potentials, had a latency of up to 2000 msec and was only observed with stimulation at frequencies of 2 Hz or greater. The response was obtained in both pregnant and non-pregnant animals, and was unaffected by hyoscine, but was abolished by cinchocaine.9. No changes in membrane potential attributable to transmission from cholinergic dilator nerves could be revealed in arteries from pregnant animals. Furthermore, high concentrations of acetylcholine had no polarizing effect on the muscle cells. It is suggested that the cholinergic dilator nerves may not act via changes in membrane potential.     

Neuronal mechanisms underlying physiological tremor

1. Tremor force was recorded during stationary isometric contractions of intrinsic hand muscles of normal subjects. Subjects maintained a steady force level between their thumb and forefinger for 30 s. The force level varied from weak (0.2 kg) to strong contractions (7 kg). These experimental conditions were the same as those in two preceding studies, where single motor-unit activity (14) and the correlation between the discharges of two simultaneously recorded motor units and physiological tremor (11) have been investigated. 2. Two alterations of the power spectra were observed at successively stronger contractions: increase of tremor amplitude and changes in the shape of the power spectrum. At all force levels, the power spectra of tremor force show the well-known decay of tremor amplitude from the lower to the higher frequencies with a local peak at 6--10 Hz. This peak does not show a significant change with respect to frequency when the force level is varied. It is shifted toward lower frequencies in a pathological condition (Parkinsonism) where the recruitment firing rates of the motor units are significantly lower than in the normal. 3. Higher frequencies (greater than 20 Hz) are barely present in the power spectrum during the very weak contractions. They become significant as the contractions become stronger. 4. The steep decay of the power spectrum toward higher frequencies has a similar slope (--43 dB/decade) as the reduction in amplitude of the unfused part of the muscle contractions with increasing stimulus rates (--38 dB/decade). The cutoff of the power spectrum above 25 Hz parallels the achievement of total fusion of muscle twitches above this rate. 5. The results are consistent with the hypothesis that the power spectrum over the range of 6--25 Hz is mainly caused by the unfused parts of the twitch contractions of motor units firing between recruitment (6--8/s) and total fusion of the twitches (25--30/s). The decline of the power spectrum toward higher frequencies can be explained by mechanical damping, which results from increasing fusion of the twitch contractions. The low-frequency part of the power spectrum is assumed to be the result of the slow force deviations produced by changes in the net output of the motoneuron pool. 6. These assumptions were supported by additional animal experiments where the number and rate of force-producing elements could be controlled. Bundles of ventral root filaments innervating cat soleus and gastrocnemius muscles were stimulated synchronously and asynchronously at a number of different rates. The force output of the strain gauge was recorded, filtered, and analyzed in the same way as the human force records. 7. Stimualtion of one nerve bundle at one fixed frequency led to a sharp peak in the power spectrum at that frequency plus peaks of decreasing height representing the harmonics of the stimulation frequency. The height of the peaks decreased at --37 dB/decade. 8...