Motor preparation in a memorised delay task

The effect on reaction time (RT) and movement time (MT) of remembering which one of several targets to move to was investigated in 18 participants who completed 416 trials in each task. On each trial, participants moved their index finger from a central, illuminated switch (the stimulus) to one of eight targets located on the circumference of a 6 cm radius circle. A visual cue (illumination of the target) informed the participant of the appropriate target. In the memorised delay task, the cued target was lit for 300 ms followed by a variable (450–750 ms) foreperiod during which the participant was required to remember the location of the target until the stimulus light was extinguished. In the non-memorised delay task, the target remained lit during the entire foreperiod (750–1050 ms) until the response was completed. At the go signal (stimulus light extinguished) participants moved as quickly and accurately as possible to the cued target. Both RT and MT were significantly (p<0.05) longer in the memorised delay task. The increase in RT shows that remembering which target imposed a greater load on motor preparation even though all the information needed for preparing the response was presented in the cue at the beginning of each trial. The increase in MT raises the possibility that movement execution was also programmed during motor preparation.     

Primate basal ganglia activity in a precued reaching task: preparation for movement

Single cell activity was recorded from the primate putamen, caudate nucleus, and globus pallidus during a precued reaching movement task. Two monkeys were trained to touch one of several target knobs mounted in front of them after an LED was lighted on the correct target. A precue was presented prior to this target go cue by a randomly varied delay interval, giving the animals partial or complete advance information about the target for the movement task. The purpose of this design was to examine neuronal activity in the major structures of the basal ganglia during the preparation phase of limb movements when varying amounts of advance information were provided to the animals. The reaction times were shortest with complete precues, intermediate with partial precues, and longest with precues containing no information, demonstrating that the animals used precue information to prepare partly or completely for the reaching movement before the target go cue was given. Changes in activity were seen in the basal ganglia during the preparatory period in 30% of neurons in putamen, 31% in caudate nucleus, and 27% in globus pallidus. Preparatory changes were stronger and more closely linked to the time of movement initiation in putamen than in caudate nucleus. Although the amount of information contained in the precues had no significant effect on preparatory activity preceding the target go cue, a directional selectivity during this period was observed for a subset of neurons with preparatory changes (15% in putamen, 11% in caudate nucleus, 14% in globus pallidus) when the precue contained information about the upcoming direction of movement. A smaller subset of neurons showed selectivity for the preparation of movement amplitude. A larger number of preparatory changes showed selectivity for the direction or amplitude of movement following the target go cue than in the delay period before the cue. The intensity of preparatory changes in activity in many cases depended on the length of the delay interval preceding the target go cue. Even following the target go cue, the intensity of the preparatory changes in activity continued to be significantly influenced by the length of the preceding delay interval for 11% of changes in putamen, 8% in caudate nucleus, and 18% in globus pallidus. This finding suggests that preparatory activity in the basal ganglia takes part in a process termed motor readiness. Behaviorally, this process was seen as a shortening of reaction time regardless of precue information for trials in which the delay interval was long and the animals showed an increased readiness to move. Preparatory activity in putamen following the target go cue was most intense in trials with a short delay interval, in which motor readiness had not achieved its maximum level prior to the go cue. The results of this study indicate that the basal ganglia are involved in multiple aspects of preparatory processing for limb movement. Preparatory processing is therefore unlikely to be divided anatomically along the functional lines examined in this study. In the basal ganglia, preparatory processing reflects both preparation for target selection and control of timing the onset of movement (motor readiness). These characteristics can be integrated in a functional scheme in which the basal ganglia are predominantly responsible for the automated execution of well-trained behavior.     

Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades

Summary The frontal eye field (FEF) and superior colliculus (SC) are thought to form two parallel systems for generating saccadic eye movements. The SC is thought classically to mediate reflex-like orienting movements. Thus it can be hypothesized that the FEF exerts a higher level control on a visual grasp reflex. To test this hypothesis we have studied the saccades of patients who have had discrete unilateral removals of frontal lobe tissue for the relief of intractable epilepsy. The responses of these patients were compared to those of normal subjects and patients with unilateral temporal lobe removals. Two tasks were used. In the first task the subject was instructed to look in the direction of a visual cue that appeared unexpectedly 12° to the left or right of a central fixation point (FP), in order to identify a patterned target that appeared 200 ms or more later. In the second anti-saccade task the subject was required to look not at the location of the cue but in the opposite direction, an equal distance from FP where after 200 ms or more the patterned target appeared. Three major observations have emerged from the present study. (a) Most frontal patients, with lesions involving both the dorsolateral and mesial cortex had long term difficulties in suppressing disallowed glances to visual stimuli that suddenly appeared in peripheral vision. (b) In such patients, saccades that were eventually directed away from the cue and towards the target were nearly always triggered by the appearance of the target itself irrespective of whether or not the anti-saccade was preceded by a disallowed glance. Those eye movements away from the cue were only rarely generated spontaneously across the blank screen during the cue-target time interval. (c) The latency of these visually-triggered saccades was very short (80–140 ms) compared to that of the correct saccades (170–200 ms) to the cue when the cue and target were on the same side, thereby suggesting that the structures removed in these patients normally trigger saccades after considerable computations have already been performed. The results support the view that the frontal lobes, particularly the dorsolateral region which contains the FEF and possibly the supplementary motor area contribute to the generation of complex saccadic eye-movement behaviour. More specifically, they appear to aid in suppressing unwanted reflex-like oculomotor activity and in triggering the appropriate volitional movements when the goal for the movement is known but not yet visible.     

A frontal cortical potential associated with saccades in humans

Summary We describe a frontal EEG potential which begins 25–35 ms before intentional saccadic eye movement. It consists of a 15–20 volt monophasic positive waveform with peak during or just after movement, and returns to EEG baseline 150–200 ms after its onset. The waveform is largest at a midline position just anterior to F_Z (10–20 system), is independent of visual input such as fixation guides, and is not related to saccade direction or amplitude. The potential is difficult to observe in some subjects and is independent of the pre-saccadic spike potential. It may be related to the discharge of single cortical neurons that signal the initiation of saccadic movements, but not their exact metrics; a possible generator is the supplementary eye fields of the dorsomedial prefrontal cortex.     

Characterization of two components of the N-like,high-threshold-activated calcium channel current in differentiated SH-SY5Y cells

Retinoic acid differentiated SH-SY5Y cells exhibit only a high-threshold-activated (–30 to –20 mV) whole cell calcium channel current. When barium was used as the charge carrier, the high-threshold-activated current showed bi-exponential inactivation kinetics during a 500 ms voltage step from –90 to +10mV. The time constants of inactivation were approximately 75 and 750 ms. The fast inactivating component was more sensitive than the slow inactivating component to steady-state inactivation at depolarized holding potentials. The calcium channel current was inhibited by externally applied cadmium (10–300 M) and gadolinium (10–30 M) as well as by high concentrations of nickel and cobalt, Conus toxin (1 M) irreversibly blocked the calcium channel current. However, the dihydropyridine agonist, BAY K 8644 (3–10 M) and antagonists, nifedipine (3–10 M) and nimodipine (10 M) did not affect either component of the calcium channel current. Agents which blocked the calcium channel current did not exhibit any selectivity for the fast inactivating over the slow inactivating component of the current. These results indicate that whilst the calcium channel current recorded in differentiated SH-SY5Y cells can be classified on the basis of the blocking agents as being of the N type, the current shows more than one form of inactivation.     

Prehension in the pigeon

Summary Eating in the pigeon involves a series of jaw movements some of which serve a prehensile function; i.e., they are utilized in the grasping and manipulation of objects. These prehensile behaviors are extremely brief (30–80 ms), produce an adjustment of jaw opening amplitude to the size of the food object, are mediated by an effector system involving a relatively small number of muscles and are amenable to both reflexive and voluntary control. This combination of structural simplicity and functional complexity suggests that the pigeon's jaw movements may provide a useful model system for the study of motor control mechanisms in targeted movements. The present report provides a classification of jaw opening movements occurring during eating and a preliminary determination of the extent to which each movement class is scaled to the size of the food object. Jaw movements were monitored during responses to spherical food pellets of six different sizes (3.2–11.1 mm in diameter) using a transducing system which produces a continuous record of gape (i.e., interbeak distance). Assignment to movement classes was then carried out using a computer-assisted scoring program. Functions relating jaw opening amplitude to target size were determined for each movement class. Four jaw movement classes were identified: Prepecks (just prior to pecking), Grasps (opening movements made during pecking but prior to contact with the target), Mandibulations (movements serving to position and transport the object within the buccal cavity) and Swallows. For two of these movement classes (Grasps, Mandibulations) jaw opening amplitude is scaled to pellet size but the scaling functions differ in ways that reflect the functional requirements of the two behaviors. However, for both movements, the data suggest that information about initial gape is used to control opening amplitude. It is concluded that during Grasping, the adjustment of opening amplitude to stimulus size involves visual inputs and open-loop control mechanisms, while for Mandibulation, that adjustment involves tactile input and closed-loop mechanisms.     

Motor cortical activity in a memorized delay task

Summary Two rhesus monkeys were trained to move a handle on a two-dimensional (2D) working surface in directions specified by a light at the plane. They first captured with the handle a light on the center of the plane and then moved the handle in the direction indicated by a peripheral light (cue signal). The signal to move (go signal) was given by turning off the center light. The following tasks were used: (a) In the non-delay task the peripheral light was turned on at the same time as the center light went off. (b) In the memorized delay task the peripheral light stayed on for 300 ms and the center light was turned off 450–750 ms later. Finally, (c) in the non-memorized delay task the peripheral light stayed on continuously whereas the center light went off 750–1050 ms after the peripheral light came on. Recordings in the arm area of the motor cortex (N= 171 cells) showed changes in single cell activity in all tasks. In both delay tasks, the neuronal population vector calculated every 20 ms after the onset of the peripheral light pointed in the direction of the upcoming movement, which was instructed by the cue light. Moreover, the strength of the population signal showed an initial peak shortly after the cue onset in both the memorized and non-memorized delay tasks but it maintained a higher level during the memorized delay period, as compared to the non-memorized task. These results indicate that the motor cortex is involved in encoding and holding in memory directional information concerning a visually cued arm movement and that these processes can be visualized using neuronal population vector analysis.     

Motor cortical activity preceding a memorized movement trajectory with an orthogonal bend

Two monkeys were trained to make an arm movement with an orthogonal bend, first up and then to the left (), following a waiting period. They held a two-dimensional manipulandum over a spot of light at the center of a planar working surface. When this light went off, the animals were required to hold the manipulandum there for 600–700 ms and then move the handle up and to the left to receive a liquid reward. There were no external signals concerning the go time or the trajectory of the movement. It was hypothesized that during that period signs of directional processing relating to the upcoming movement would be identified in the motor cortex. Following 20 trials of the memorized movement trajectory, 40 trials of visually triggered movements in radially arranged directions were performed. The activity of 137 single cells in the motor cortex was recorded extracellularly during performance of the task. It was found that 62.8% of the cells changed activity during the memorized waiting period. During the waiting period, the population vector (Georgopoulos et al. 1983, 1984) began to grow approximately 130 ms after the center light was turned off; it pointed first in the direction of the second part of the memorized movement () and then rotated clockwise towards the direction of the initial part of the movement (). These findings indicate processing of directional information during the waiting period preceding the memorized movement. This conclusion was supported by the results of experiments in ten human subjects, who performed the same memorized movement (). In 10% of the trials a visual stimulus was shown in radially arranged directions in which the subjects had to move; this stimulus was shown at 0, 200, and 400 ms from the time the center light was turned off. We found that as the interval increased the reaction time shortened for the visual stimulus that was in the same direction as the upward component of the memorized movement.     

Changing patterns of eye-head coordination during 6 h of optically reversed vision

Summary 1) This study investigates the early development of adaptive changes in oculomotor function associated with coordinated eye-head tracking of the optically reversed image of an earth-fixed target seen through horizontally reversing dove prism goggles attached to the skull. 2) Two tasks comprised a) fixation of a single target during head rotation which causes the seen target's image to move in the direction of head motion by an amount exactly equal to the head movement itself (the 1-Target task), and b) change of gaze onto a displaced target with head free to move (2-Target task). 3) The 1-Target task requires the eyes to move in a direction opposite to that of the normal vestibulo-ocular reflex (VOR). The 2-Target task is identical, except that reorientation onto the new target calls for an initial saccadic eye movement in a direction opposite to that of the ensuing head movement, which is contrary to the normal pattern of eye-head coordination during gaze shifts. 4) Eye (EOG) and head (potentiometer) movements were continuously recorded (0–250 Hz) in an apparatus which permitted sudden, unexpected, electromagnetic braking of the head movement, either just before or during the intended manuvre. 5) Early adaptive strategies employed reduction of VOR gain, rearrangement of timing, amplitude and shape of catch-up saccades and the introduction of centrally programmed eye movements uncovered by the braking manuvres. 6) All of these phenomena were detectable in an initial series of 60 trials, in which the total exposure to visual-vestibular conflict was less than 30 s. They became more systematized and more marked after 6 h of active reversed vision experience. 7) Specifically, mean VOR gain, measured within the first 80 ms of head movement (deemed free of visuomotor influence), became markedly attenuated (25% in the first test series; 66% after 6 h of active visionreversed exercise). In addition (not included in the above percentages) there were numerous occasions of complete absence of measurable VOR during head rotation, in both the first and final test series. 8) In the 1-Target task, the latency of the first catch-up saccade (re onset of head movement) tended to offset residual VOR by becoming shortened to the point of synchrony with head movement onset. This saccade (not present in control tests) continued to occur on those occasions when the head was unpredictably prevented from moving, and when head movements were made in the dark. 9) Sometimes these initial saccades began normally, but glissaded in a graded manner into a smooth pursuitlike trajectory, resembling the classical glissade associated with pulse-step mismatch in the saccade generating system. 10) All these events represent embryo facsimilies of more advanced adaptive manuvres seen in an earlier study extending over 19 days of reversed vision experience. 11) It is concluded that the adaptive process is a multifactorial one, exhibiting idiosyncracy in individuals and from time to time. Some phenomena appear in embryo form within seconds of exposure to the new condition. Others, such as progressive VOR gain attenuation, introduction of central programming and advanced strategies of the glissade type, developed more slowly over the 6 h period of these experiments.     

The role of the claustrum in the bilateral control of frontal oculomotor neurons in the cat

Summary The effect of claustrum (CL) stimulation on the spontaneous unitary activity of ipsi and contralateral frontal oculomotor neurons, was studied in chloralose-anaesthetized cats. A total of 205 units was bilaterally recorded in the medial oculomotor area, homologous of the primate frontal eye fields 127 neurons were identified as projecting to the superior colliculus; for 33 of these last units stimulation of the ipsilateral CL provoked an excitatory effect lasting 10–25 ms and appearing with a latency of 5–15 ms; on 8 units the excitatory effect was followed by an inhibition lasting 100–250 ms. Ninety-eight of the 127 neurons were also tested through activation of the contralateral CL: 13 cells showed an excitatory effect lasting 10–35 ms and appearing with a latency of 20–50 ms. In three of the thirteen units the excitatory effect was followed by an inhibition lasting 100–150 ms. Complete section of the corpus callosum abolished the contralateral CL effect, suggesting the existence of a direct claustro-contralateral oculomotor cortex pathway running through the corpus callosum. The results could support the hypothesis that the CL may play a role in the bilateral control of the visuomotor performance.     

Voltage-dependent noradrenergic modulation of ω-conotoxin-sensitive Ca2+ channels in human neuroblastoma IMR32 cells

High-threshold (HVA) Ca²⁺ channels of human neuroblastoma IMR32 cells were effectively inhibited by noradrenaline. At potentials between –20 mV and +10 mV, micromolar concentrations of noradrenaline induced a 50%–70% depression of HVA Ba²⁺ currents and a prolongation of their activation kinetics. Both effects were relieved at more positive voltages or by applying strong conditioning pre-pulses (facilitation). Facilitation restored the rapid activation of HVA channels and recruited about 80% of the noradrenaline-inhibited channels at rest. Re-inhibition of Ca²⁺ channels after facilitation was slow ( _r 36–45 ms) and voltage-independent between –30 mV and –90 mV. The inhibitory action of noradrenaline was dose-dependent (IC₅₀=84 nM), mediated by ₂-drenergic receptors and selective for -conotoxin-sensitive Ca²⁺ channels, which represent the majority of HVA channels expressed by IMR32 cells. The action of noradrenaline was mimicked by intracellular applications of GTP[S] and prevented by GDP[S] or by pre-incubation with pertussis toxin. The time course of noradrenaline inhibition measured during fast application (onset) and wash-out (offset) of the drug were independent of saturating agonist concentrations (10–50 M) and developed with mean time constants of 0.56 s ( _on) and 3.6 s ( _off) respectively. The data could be simulated by a kinetic model in which a G protein is assumed to modify directly the voltage-dependent gating of Ca²⁺ channels. Noradrenaline-modified channels are mostly inhibited at rest and can be recruited in a steep voltage-dependent manner with increasing voltages.     

Phospholipase A2 (PLA2) activity in bovine pulmonary artery endothelial cells

We have investigated the role of recombinant human interleukin-1 (rIL-1) and recombinant human tumor necrosis factor (rTNF-) on PLA₂ activity, protein synthesis and eicosanoid production in bovine pulmonary artery endothelial cells. Cellular PLA₂ activity increased 4-fold and production of PGE₂ increased 3-fold at 1–2 hrs in the presence of 10 units/ml rIL-1. PLA₂ activity increased 3-fold at 30 min and PGE₂ production increased 2-fold with 5×10^–9 M rTNF-. The data show that endothelial cells respond more rapidly to rIL-1 (2–6 hr) and rTNF- (30 min) than do chondrocytes and synovial cells (6–16 hrs), suggesting endothelial cells may play a primary role in initiating the inflammatory response.     

Long latency reflexes to imposed displacements of the human wrist: Dependence on duration of movement

Summary Reflex EMG responses to angular displacements of the wrist joint were recorded from 12 normal human volunteers. A mechanical stop was used to suddenly arrest displacements at varying times following the onset of the stimulus. With unrestricted movement of the handle, the EMG response consisted of an early component (M1) with a latency of 30–35 ms and a long-latency component (M2–3) beginning 55–65 ms after the onset of the displacement. When the displacements were arrested prior to a critical time occurring between 40 and 50 ms after the onset (mean of 44 ms), the M2–3 component of the response was not present. Increasing the duration of the displacement beyond this time resulted in a rapid increase in the size of M2–3. Facilitation provided by volitional intent to oppose the perturbation was not sufficient to generate an M2–3 response to either a brief, low velocity displacement produced by the torque motor or to a phasic, high velocity stretch produced by a tendon tap.The timing relationships between the onset latency of M2 and the minimum duration of displacement required to generate an M2–3 response are not easily reconciled with the notion that the segmentation of the EMG responses into components is mediated by repeated activation of the same central reflex pathway by phasic afferent bursts. Two mechanisms that could account for these results are either inhibition in response to the sudden stop of phasically-active linking interneurons which are part of the long latency pathway, or the loss of an essential convergent facilitatory input which serves to monitor the continuation of the movement.This research was supported by Medical Research Council of Canada grants MA 4209 and MA 5218     

Direct immuno-electron microscopy and some morphological features of hog cholera virus

Summary Characteristic particles of hog cholera virus were identified by direct immuno-electron microscopy. The virion is 40–50m, often asymmetrically shaped, and is enveloped in a membrane that bears 12–15 m surface projections. The surface projections are shear-sensitive and are antigenically different from the virion's envelope. They may represent hog cholera virus soluble antigen.     

Spontaneous and GABA-evoked chloride channels on pituitary intermediate lobe cells and their internal Ca requirements

On porcine intermediate lobe (IL) endocrine cells, spontaneously opening chloride channels have been studied and compared to GABA-A activated chloride channels. Elementary currents were recorded mainly from outside-out patches excised from IL cells maintained in culture for 1–4 weeks. Spontaneous inward currents were observed in Cs-loaded cells after replacing Na in the extracellular medium by the impermeant ion choline. This activity, at an internal calcium concentration of 10^–8 M corresponded to a channel for chloride ions with a main conductance level of 26 pS, and substates around 11 pS. The sequence of permeabilities to halides was I>Br>Cl. These conductance characteristics were common to the GABA-operated channels which also showed a main conductance substate of 23–31 pS. The open time of the 26 pS level mostly encountered in spontaneous activity, was distributed along two modes: one, the most frequent, around 1 ms, and the other around 4 ms. This latter mode was the predominant one observed during GABA and isoguvacine applications but in addition a bursting activity of 19 ms duration was also seen. Specific GABA-A receptor antagonists (bicuculline and SR 42641, 1 M) blocked activity evoked by GABA (1–10 M), but did not affect spontaneous events. These spontaneous Cl events were only observed in a restricted range of internal Ca concentrations, i.e. between 1 nM and 0.1 M, and were practically abolished at Ca_i 1 M. The GABA-induced activity of Cl channels was also Ca-sensitive, being reduced when Ca_i reached 1 M.     

Integration in trigeminal premotor interneurones in the cat

A population of last-order interneurones within the rostrodorsal part of the oral nucleus of the spinal trigeminal tract (NVspo-) has been investigated in 21 chloralose anaesthetised cats. The neurones were identified by their antidromic (AD) response to microstimulation (median current 9 A, range 3–39 A) of the ipsior the contralateral masseteric subnucleus of the trigeminal motor nucleus. Fifty-one of 113 interneurones tested were discharged from the ipsilateral and eight from the contralateral motor nucleus. The average conduction time was 0.50 ms from the ipsilateral and 0.74 ms from the contralateral motoneurone pool. Conduction velocities of the axons ranged from 2.0 to 14.0 ms. The pattern of primary afferent input onto the selected neurones was analysed by graded electrical stimulation of dissected trigeminal nerves. Low-threshold afferents innervating the intraoral mucosa including the tongue and the perioral skin of the lower lip were the most effective inputs, as judged from both the frequency of occurrence and from the latencies of the evoked spike discharges. Ninety-six percent of the neurones responded to stimulation of the inferior alveolar nerve (Alv inf) and 83% responded to stimulation of the lingual nerve (Ling). The median threshold strength required to evoke the Alv inf and the Ling responses was 1.7 T (range 1.0–3.6 T) and 1.3 T (range 1.0–5.0 T), respectively. The median latency to spike discharges evoked by the Alv inf was 2.0 ms (range 1.3–4.8 ms) and to the Ling it was 2.5 ms (range 1.4–7.0 ms). Action potentials elicited by stimulation of the masseteric and digastric nerves were observed in 40% and 10% of the neurones, respectively. These responses, which had median latencies of more than 8 ms (range 4.7–16.0 ms), were only seen at stimulation intensities above 2 T (range 2.5–25 T). An input from the maxillary whisker nerve was seen in only one case. Postspike averages of the extracellular field potentials within the trigeminal motoneurone subnuclei evoked by interneuronal spikes were made in a subsample of 51 NVspo- neurones activated by iontophoresis of L-glutamic acid. Excitatory synaptic effects within the masseteric subnucleus were observed in eight cases. An inhibitory effect was seen in one case. One specific neurone gave an excitatory extracellular field potential within the digastric motoneurone subnucleus. This interneurone was AD activated from the digastric, but not from the masseteric subnucleus. The physiological properties of the NVspo--mass interneurones are discussed in relation to their suggested roles in the phase-dependent control of the trigeminal motoneurones during oro-facial masticatory behaviours.     

Effects of sleep deprivation on the activity of selected metabolic enzymes in skeletal muscle

Summary The present study gives the results of a comparison of the recorded and true tibia-calcaneal angles in 17 normal subjects and in 14 patients with abnormally hypoextensible non contracting triceps. 1. For a minimal passive torque, the difference between true and recorded angles varied considerably from one individual to another. The means and ranges for the two groups were respectively: –8 (+7, –21) and –7 (+5, –20). 2. When the passive torque increased as a result of slow passive lengthening of the muscle, the true curve was steeper than the recorded one, owing to differences between the two angle measurements. For each of the two groups the differences in means and ranges were respectively: 6 (0, +13.5) and 8 (3, 12). 3. Subjects made isometric voluntary contractions of the triceps surae at fixed angles which corresponded to step by step muscle lengthening. The resulting true curve was much steeper than the recorded curve. The differences in means and ranges were: 7 (1.5, +15) in children of the two groups and respectively 3 (0, +9) and 12 (10, 14) in adults of the two groups. The present results show that this methodology was the only reliable way of correctly obtaining passive and active torque-angle curves, measuring differences between subjects, appreciating the effects of treatments and these by ascertaining whether or not trophic muscle regulation was defective.     

Time constants of facilitation and depression in Renshaw cell responses to random stimulation of motor axons

Summary In 9 adult anaesthetized cats, 22 lumbosacral Renshaw cells recorded with NaCl-filled micropipettes were activated by random stimulation of ventral roots or peripheral nerves. The stimulus patterns had mean rates of 9.5–13 or 20–23 or 45 pulses per second and were pseudo-Poisson; short intervals below ca. 5 ms (except in two cases) were excluded. The Renshaw cell responses were evaluated by two kinds of peristimulus-time histograms (PSTHs). Conventional PSTHs were calculated by averaging the Renshaw cell discharge with respect to all the stimuli in a train. These PSTHs showed an early excitatory response which was often followed by a longer-lasting slight reduction of the discharge probability. These two response components were positively correlated. Conditional PSTHs were determined by averaging the Renshaw cell discharge with respect to the second (test) stimulus in pairs of stimuli which were separated by varied intervals, . The direct effect of the first conditional response was subtracted from the excitation following the second (test) stimulus so as to isolate the effect caused by the second stimulus per se. After such a correction, the effect of the first conditioning stimulus showed pure depression, pure facilitation or mixed facilitation/depression. Analysis of such conditioning curves yielded two time constants of facilitation (ranges: ca. 4–35 ms and 93–102 ms) and two of depression (ranges: ca. 7–25 ms and 50–161 ms). It is concluded that these time constants are compatible with processes of short-term synaptic plasticity known from other synapses. Other processes such as afterhyperpolarization and mutual inhibition probably are of less importance.     

Control of recurrent inhibition of the lateral geniculate nucleus by afferents from the superior colliculus of the rabbit: a possible mechanism of saccadic suppression

Summary Stimulation of the ipsilateral superior colliculus elicited a short burst of discharges of the recurrent inhibitory interneurones in the geniculocortical pathway of the rabbit. The most effective stimulating sites for this excitation were located in the deep layers rather than the superficial layers of the superior colliculus. The short latency of the response (2.3±0.6 ms) implied an oligo-synaptic excitatory pathway from the deep layers of the superior colliculus to the recurrent interneurones located in the caudal reticular nucleus of the thalamus. Following the excitation of the inter-neurone, there was a prolonged inhibition which started 10–30 ms and ended 150 ms after the collicular stimulation. The maximal inhibition occurred 50–70 ms after the stimulation. The effects of collicular stimulation on the recurrent inhibitory interneurones may be concerned with the inhibition of the visual pathway during saccades and with the disinhibition of facilitation during fixation of a new visual target.     

Cytokine gene polymorphisms in ischaemic heart disease: investigation using family-based tests of association

Atherosclerosis has an inflammatory basis, with cytokines, cellular adhesion molecules and pro-inflammatory cells having important roles in the initiation and progression of this process. Interleukin (IL) 6, IL-10 and transforming growth factor (TGF) ₁ have been proposed as important modulators of the atherosclerotic process, with IL-6 having a pro-inflammatory, atherogenic effect and IL-10 and TGF-₁ having anti-inflammatory, protective roles. The possible role of functional polymorphisms in the promoter regions of the IL-6, IL-10 and TGF-₁ genes in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. We genotyped 1,012 individuals from 386 families with at least one member prematurely affected with IHD. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test, no association between any of the IL-6 –174G/C, IL-10 –1082G/A and TGF-₁ –509C/T polymorphisms and IHD was found. Our data demonstrate that, in an Irish population, these polymorphisms are not associated with IHD.