Post-stimulus Period Research Articles

The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.

Vesamicol blocks the recovery, by recycling cholinergic electromotor synaptic vesicles, of the biophysical characteristics of the reserve population

The effect of vesamicol on the ability of recycling cholinergic synaptic vesicles to recover, during a period of post-stimulation rest, the biophysical properties of the reserve pool was studied in prestimulated perfused blocks of the electric organ of the electric ray, Torpedo marmorata, a tissue rich in cholinergic synapses. The effect of the drug was analysed by high-resolution centrifugal density-gradient fractionation in a zonal rotor of the extracted vesicles. The two vesicle fractions were identified by their ATP and acetylcholine content and the recycled vesicles by their acquisition of [ 3H]acetylcholine derived from [ 3H]acetate in the perfusate. Vesamicol (10 μM) blocked the uptake of tritiated acetylcholine by recycled vesicles and also prevented them from rejoining the reserve pool. This is consistent with a previously formulated model of the recovery process, whereby the increase in the acetylcholine and ATP content of the recycled vesicles which takes place during a post-stimulus period of rest increases their osmotic load and thus their content of free water. Vesamicol, by blocking acetylcholine uptake, also blocks rehydration of the recycled vesicles and thus the accompanying decrease in their density to the value characteristic of fully charged vesicles.

Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia.

1. To determine the afferent pathways mediating pharyngeal dilator muscle activation in response to negative airway pressure in man, we recorded genioglossus electromyogram (EMG) activity (via intra-oral bipolar surface electrodes) in response to 500 ms duration pressure stimuli of -15 and -25 cm H2O in normal, conscious, supine subjects relaxed at end-expiration; responses were compared before and after upper airway anaesthesia. 2. Six rectified and integrated EMG responses were bin averaged for pressure stimuli applied with the glottis open (GO) and closed (GC) and to the outside of the face only (controls). Response magnitude was quantified as the ratio of the EMG activity for an 80 ms post-stimulus period (before the subject's reaction time for tongue protrusion) to an 80 ms pre-stimulus period. 3. In eight subjects, upper airway anaesthesia reduced the EMG responses with GC to a level indistinguishable from controls. After anaesthesia, responses with GO remained higher than those with GC. 4. With GC, the mean EMG responses decreased by 43% after selective anaesthesia of the nasal mucosa (trigeminal nerves) in two subjects, 32% after selective anaesthesia of the laryngeal mucosa (superior laryngeal nerves) in six subjects and by 21% after selective anaesthesia of the oropharyngeal mucosa (glossopharyngeal and lingual nerves) in four subjects. 5. We conclude that upper airway afferents mediate pharyngeal dilator muscle activation in response to negative pressure with GC and that subglottal receptors caused the increased activation with GO. With GC, the trigeminal and superior laryngeal nerves mediate an important component of the responses with the glossopharyngeal nerves playing a less important role.

Facilitatory effect of hypothalamo-neurophypophysial tract stimulation on milk ejection frequency in the lactating rat

The relative contribution of magnocellular and parvocellular neurones to the patterning of milk ejections was studied by activation of various parts of the hypothalamo-neurohypophysial tract. During suckling of anaesthetised lactating rats, electrical stimulation of the neurohypophysis/neural stalk (15 Hz, 1.5 s on 1.5 s off , 10 min) evoked an increased frequency of milk ejections as detected by intramammary pressure recording. Bilateral stimulation of the paraventricular nuclei produced a similar facilitation in the post-stimulus period, but stimulation of the supraoptic nuclei (with either low current or current sufficient to evoke peripheral oxytocin release) had no effect on the occurrence of milk ejections. These data are consistent with the hypothesis that parvocellular but not magnocellular neurones participate in the regulation of milk ejection frequency.

Simulation of auditory-neural transduction: further studies.

A computational model of mechanical to neural transduction at the hair cell-auditory-nerve synapse is presented. It produces a stream of events (spikes) that are precisely located in time in response to an arbitrary stimulus and is intended for use as an input to automatic speech recognition systems as well as a contribution to the theory of the origin of auditory-nerve spike activity. The behavior of the model is compared to data from animal studies in the following tests: (a) rate-intensity functions for adapted and unadapted responding; (b) two-component short-term adaptation; (c) frequency-limited phase locking of events; (d) additivity of responding following stimulus-intensity increases and decreases; (e) recovery of spontaneous activity following stimulus offset; and (f) recovery of ability to respond to a second stimulus following offset of a first stimulus. The behavior of the model compares well with empirical data but discrepancies in tests (d) and (f) point to the need for further development. Additional functions that have been successfully simulated in previous tests include realistic interspike-interval histograms for silence and intense sinusoidal stimuli, realistic poststimulus period histograms at various intensities and nonmonotonic functions relating incremental and decremental responses to background stimulus intensity. The model is computationally convenient and well suited to use in automatic recognition devices that use models of the peripheral auditory system as input devices. It is particularly well suited to devices that require stimulus phase information to be preserved at low frequencies.

Cholinergic Receptor-regulation of Potassium Channels and Potassium Transport in Human Submandibular Acinar Cells

The cholinergic receptor-regulation of K+ transport was studied in human submandibular glands. Acetylcholine stimulation 10 mumol/L results in an increase in membrane permeability (86Rb+ efflux) for, and a net efflux of, K+ ions from the glandular tissue. In the post-stimulus period, there is a net re-uptake of K+ ions into the tissue. Patch-clamp electrophysiological techniques were employed to demonstrate the presence of a large conductance K+ selective ion channel in the basolateral membranes of isolated human submandibular acinar cells. The patch-clamp results indicate that this voltage- and calcium-activated K+ channel operates to regulate the K+ permeability in both the resting and acetylcholine-stimulated acinar cells. We discuss the role of the K+ channel, K+ efflux, and K+ re-uptake in relation to stimulus-secretion coupling.

Potassium uptake in the mouse submandibular gland is dependent on chloride and sodium and abolished by piretanide.

Nervous or hormonal stimulation of salivary secretion in vivo is associated with a pronounced efflux of K+ from the secretory, acinar cells into the blood. This K+ efflux is followed in the post-stimulus period by a reuptake of K+ into the glandular tissue. In the present study we monitor the changes in [K+] of physiological solutions perfusing a flow chamber containing isolated segments of mouse submandibular glands. Nervous stimulation or the application of exogenous acetylcholine (ACh, 10(-5) M) to the isolated glandular tissue results in characteristic changes in the [K+] of the superfusate, indicating net K+ release followed by K+ reuptake. The post-stimulus reuptake of K+ is shown to be susceptible to blockade by either ouabain (10(-3) M) or piretanide (10(-4) M). The reuptake was markedly attenuated if Cl- in the superfusate was replaced by either NO3- or SO4(2-). The K+ uptake was, however, unaffected when Br- replaced Cl- in the superfusate. Similar effects were observed in the unstimulated glandular tissues. The introduction of Cl-(-)free media containing either NO3- or SO4(2-) resulted in a loss of K+ from the tissue which was followed, upon reintroduction of Cl-, by a pronounced uptake of K+. When Br- was substituted for Cl- there was very little change in [K+] upon removal or reintroduction of Cl-. The uptake of K+ induced by reintroduction of Cl- after a period of NO3- or SO4(2-) superfusion was blocked by both ouabain and piretanide. This uptake of K+ was also dependent on the presence of extracellular Na+. Both Cl- and Na+ had to be present in the superfusing medium for K+ uptake to be fully manifest. These findings indicate that the K+ uptake observed in both the resting and stimulated submandibular gland cannot be explained as solely due to the activity of the Na+-K+-adenosine triphosphatase (Na+-K+-ATPase). The demonstrated anionic selectivity, dependence on extracellular Na+ and susceptibility to blockade by the diuretic piretanide would strongly suggest that a coupled Na+-K+-Cl- co-transport system operates in submandibular glands as it does in other transporting epithelia to achieve K+ uptake.

Parvocellular neurosecretory neurons: converging inputs after saphenous nerve and hypovolemic stimulations in the rat.

Effects of saphenous nerve stimulation and hemorrhage on discharge activity of parvocellular neurosecretory (PC) cells of the paraventricular hypothalamic nucleus (PVN) were studied in anesthetized rats. The PC cells were identified in the PVN with the criteria that units recorded in the PVN showed an antidromically conducted spike after median eminence but not after posterior pituitary stimulation of 0.45 mA intensity and were demonstrated histologically to be located in the parvocellular regions of the PVN. Saphenous nerve stimulation at 4 Hz repetition and of 3 mA intensity increased the discharge rate of 13 of the 52 PC cells tested. These excited cells exhibited a synaptically mediated excitation during post-stimulus period on peristimulus time histograms constructed during 1 Hz stimulation. Hemorrhage (4 ml/kg b.w.) activated 7 of the 10 PC cells tested which had been excited by saphenous nerve stimulation. Both saphenous nerve stimulation and hemorrhage increased immunoreactive adrenocorticotropic hormone (ACTH) in the plasma in the anesthetized rats. These data support the view that synergistic potentiation of ACTH secretion reported to occur after noxious and hypovolemic stimuli depends at least in part on the interaction between afferent neural signals originating from noxious and cardiovascular receptors on their way up to corticotropin-releasing factor (CRF)-secreting PVN neurons.

Brainstem activation of the adrenal medulla in the cat

Stimulation of the locus coeruleus in 40 cats leads to generalized activation of the sympathetic nervous system characterized by an immediate pressor response which was followed in the post-stimulus period by an increase of 49 ± 10and44 ± 6% in common carotid arterial resistance ipsilateral and contralateral to stimulation, respectively. This later response was not affected by vagotomy or bilateral cervical sympathectomy but was blocked by high spinal cord section. The post-stimulus carotid vasoconstriction response could be entirely eliminated by acute bilateral physiological adrenalectomy in the form of adrenal hilar clamping, an effect which was reversible if the clamps were removed. The carotid vasoconstrictor response was associated with a rise in the circulating level of noradrenaline (260%) and adrenaline (196%), which was prevented by clamping the adrenal hilum. This response was not mediated via the hypothalamus because it persisted in the decerebrate animal, nor was it merely excitation of fibers of passage since it was reproduced by microinjection of glutamate into the locus coeruleus. The response was blocked by phentolamine suggesting it is mediated by α-adrenoceptors. These data represent the first conclusive demonstration that cell bodies in the brainstem are capable of activating the adrenal medulla. This fact is central to our present concept of the organization of the sympatho-adrenal axis.

Calling Tactics in Crinia georgiana (Anura: Myobatrachidae): Alternation and Variation in Call Duration

Male Crinia georgiana actively alternate with artificial stimulus pulses at rates of stimulation encountered in natural choruses. Males also increase the duration of their calls by adding notes in response to increased frequency of acoustic stimulation. We interpret this result to be an adaptation that allows males to maintain broadcasting periods (interference free) at least as long as those ofcompetitors. Alternation is facilitated by a 0.4-s post-stimulus lag period. Evoked calls are not initiated during the lag period which, together with the 0.3-s stimulus pulse, approximates the duration of a three-note call; such calls predominate in natural choruses. Evoked calls that were likely to overlap a following stimulus pulse were terminated, minimizing interference and demonstrating the importance of effective signal transmission.

Correcting baseline drift artifact in slow potential recording.

ABSTRACTA problem frequently encountered by investigators measuring scalp‐recorded DC potentials is baseline drift artifact. The sources of baseline drift are many and it is often very difficult to remove drift from the primary data. The problem is particularly acute when long recording epochs are under investigation. The present paper proposes a software solution. A FORTRAN IV computer program defines drift as a significant linear trend in prestimulus voltage on successive experimental trials. When drift is determined to be present, its slope is computed and statistically removed from the data in the poststimulus (response) period. A sample data set is included which demonstrates the method's marked improvement of signal‐to‐noise ratios, as represented by reduced error variance and improved statistical discrimination between the independent variables of an experiment.

Induction of decidualization in rats by the intrauterine infusion of prostaglandins.

Alzet Osmotic minipumps, attached to the ovarian end of the uterine horn, were used to infuse prostaglandins unilaterally into the uterine lumen of mature ovariectomized rats which had been treated with a regimen of estradiol and progesterone to sensitize the uteri for the decidual cell reaction. The rats were treated with indomethacin prior to the insertion of the pumps to inhibit endogenous prostaglandin production. Decidualization was assessed 4 days later by determining uterine weights and by histological examination; the geometric mean weight of horns infused with vehicle (1 p1/h) was 332 mg, significantly less than those of horns infused with prostaglandin E3 (1 pg/h), prostaglandin F2 � (1 pg/h) or combined prostaglandins E2 and F3 � (geometric means of 939, 763 and 1114 mg, respectively). The dose-response relationship for prostaglandins E3 and F2 � did not differ significantly. To determine if prostaglandin synthesis is required throughout the post-stimulus period to obtain full decidualization, rats were given a single injection of 2 mg indomethacin either 2 h before, or 12, 24 or 48 h after the deciduogenic stimulus, a unilateral intrauterine injection of 50 p1 sesame oil. As assessed by uterine weights 4 days later, decidualization was reduced by indomethacin treatment. In the stimulated, compared to the nonstimulated horns, uterine concentrations of prostaglandins E and F were markedly elevated 5 mm after intraluminal oil, but returned to concentrations which were not significantly higher by 6 h and 24 h, respectively. These data suggest that prostaglandins are involved throughout the transformation of endometrial stromal cells to decidual cells in rats.

Eye-head coordination during optokinetic stimulation in squirrel monkeys.

Head and eye movements in the yaw plane were recorded during and after optokinetic stimulation in squirrel monkeys. 1) Phasic or tonic head deviations to the side of the ocular quick phase occurred in 94% of total recordings (n = 50) during the perstimulus period, and in 75% of recordings (n = 49) during the poststimulus period. Magnitude of mean head deviation was significantly different between perstimulus and poststimulus periods. 2) Head nystagmus associated with eye nystagmus was consistently observed in seven of nine squirrel monkeys during optokinetic stimulation. Squirrel monkeys are thereby less prone to display head nystagmus than either guinea pigs, pigeons or chickens. 3) Slow phase speeds of coupled head and eye nystagmus were subjected to statistical analysis. A highly significant negative correlation was found between slow phase head and eye speeds. The correlation coefficient was - 0.81 at 60 degrees / sec stimulus (n = 119) and -0.72 at 100 degrees / sec stimulus (n = 131). The gaze speed, calculated by summing the head and eye speeds, was 59.1 plus or minus 6.8 / sec at 60 degrees / sec and 92.2 plus or minus 11.4 at 100 degrees / sec stimulus. There was no significant difference between the gaze speed in a free head condition and the eye speed when the head was fixed.

Reflex effects of muscle afferents on antagonist studied on single firing motor units in man

The effects of electrical stimulation of mixed nerves and of the evoked tendon reflex on single firing MUs of antagonists were investigated. The following muscles were studied: m. biceps fem., m. tibialis ant. and m. triceps surae. Under a weak voluntary contraction MU potentials were picked up. Post-stimulus histograms of MU potentials were plotted and the duration of interspike intervals in the post-stimulus period was compared with that in the prestimulus period. Under electrical stimulation of the nerve (Ia afferents) a distinct reciprocal inhibition was observed on MUs of all the 3 investigated muscles. In some cases a weak excitatory drive could be revealed along with the reciprocal inhibition. The tendon (knee) reflex was accompanied by a distinct excitatory effect on MUs of the antagonist. The dependence between the efficiency of the inhibitory volley and the moment within an interspike interval at which the volley arrived was found. The lengthening of an interval was observed only when an inhibitory drive occurred close to its end. The peculiarities of reciprocal inhibition in the firing motoneurone, as well as the possible mechanism of the excitatory effect on the antagonist accompanying the tendon reflex, are discussed.

Effects of perception versus imagery on later recognition of visual patterns

Three experiments were conducted to determine the role of imagery in aiding memory for visual information and to compare its effectiveness relative to direct perception. Subjects engaged in orienting tasks in which they had to decide whether the second of two sequentially presented meaningless patterns was a part of the first. They later received unexpected recognition tests for the original drawings. Increasing the interval between patterns by adding an extra post-stimulus period for imaginal processing improved later recognition scores. Experiments comparing continued perception with an equal blank interval suggested that periods of direct perception and of imagery are about equally effective in promoting memory. The results are discussed in the frame work of Craik and Lockhart (1972) with regard to type I and type II processing, and in the light of Neisser's (1967) view on imagery and perception.

Measurement of the evoked cardiac response: The problem of prestimulus variability

This paper discusses the problem of prestimulus variability in cardiac activity and its implications for the measurement of evoked cardiac responses (ECRs). Two methods which have been proposed to reduce error arising from respiratory sinus arrhythmia (SA) were reviewed critically. The first approach attempts to control only for the error associated with the sampling of the prestimulus level. This is considered inappropriate since it does not take into account the continuation of SA into the poststimulus period. The second approach reviewed was time series analysis which provides an elegant statistical solution of the problem. Unfortunately, the application of time series analysis has not yet been evaluated for adult cardiac data. A third approach which utilizes an adjustment for SA by employing the actual prestimulus values of an SA cycle was proposed. The application of this technique in the case of a pseudostimulus demonstrated that correction for SA results in significantly smaller ‘responses’ with less variance than does a conventional procedure which does not take prestimulus variability into account.

Ontogeny of behavioral responsiveness to sound in the chick embryo as indicated by electrical recordings of motility.

The primary purpose of these experiments was to gather normative behavioral data regarding the ontogeny of responsiveness to sound in the chicken embryo. As a prerequisite, a sensitive ane accurate method for recording embryonic motility was developed (Experiment 1). By means of platinum electrodes inserted just beneath the shell membrane, potentials resulting from heartbeat and movement were recorded on a polygraph. The technique was found to be effective when applied to chick embryos 6 days and older. Correlations between visual observations of activity and the records produced by the electronic technique substantiated its accuracy. Behavioral responses of chick embryos (Stages 39-43) to acoustic stimulation (Experiment 2) were then recorded. High-intensity (115-dB SPL) tones of 400, 700, and 1400 Hz were used as stimuli. The earliest consistent responses were recorded from Stage 40 (ca. Days 14-15) subjects; the 700 and 1400 Hz tones produced statistically reliable inhibition of movement during the stimulus period compared with the post-stimulus period. Reliable increases in movement during the stimulus period were first recorded at Stage 42 (ca. Days 16-17) in response to 700 and 1400 Hz and at Stage 43 (ca. Days 17-18) in response to 400 Hz.

Reward-associated excitation and pain-associated inhibition lasting seconds in rat medial pallidal units

Prolonged changes during 10 sec poststimulus periods in unit firing rate following stimuli (0.2 sec, 100 Hz, 0.5 msec cathodal pulses) at reward sites in medial forebrain bundle and aversive midbrain reticular sites have been observed in unanesthetized postcollicular cerveau isolé rats. However, longlasting medial forebrain bundle-elicited inhibition and reticular-elicited excitation converged on single cells only in intralaminar thalamus. Since these opposite effects had a comparatively long duration, the present study postulated that a related brain region might also show opposite medial forebrain bundle and reticular responses, but the inverse of those seen in intralaminar thalamus. Using similar methods, convergence on single units of prolonged excitation by medial forebrain bundle and by reticular stimuli was typical in internal capsule and to a lesser extent amygdala. Ventral anterior-ventral lateral nuclei of thalamus were characterized by converging inhibition. Contrasting actions of the stimuli which might involve presynaptic interactions were observed in lateral pallidum. However, direct opposite effects, medial forebrain bundle-elicited excitation and reticular-elicited inhibition, were demonstrated and confined anatomically to a medial pallidal region. The opposite responses summated or cancelled when the medial forebrain bundle and reticular stimuli were given simultaneously. A medial pallidal-intralaminar thalamus system may be central to the neural coding of certain affective states, integrating these with motor control and sensory information.

Reward-associated inhibition and pain-associated excitation lasting seconds in single intralaminar thalamic units.

Reward sites in the medial forebrain bundle (MFB) and aversive reticular sites (RET) send projections to the medial thalamus and elicit opposite changes in intralaminar unit activity with durations (seconds) similar to those of subjective sensations produced by reinforcing stimuli. To describe the anatomical distribution and to estimate the number of cells showing prolonged rate changes (10-sec poststimulus periods) to MFB and RET stimuli (0.2 sec, 100 Hz, 0.5-msec cathodal pulses), 427 units were recorded in 15 unanesthetized post-collicular cerveau isole´rats. Longlasting MFB-elicited inhibition and RET-elicited excitation converged on single cells located in the intralaminar thalamus. Convergence of MFB- and RET-evoked excitation was found in the habenula, reticular formation, superior colliculus and thalamus; converging inhibition occurred in the cerebral cortex, reticular formation and thalamus. In the intralaminar thalamus, there was more variation and habituation of unit responses to multimodal sensory stimuli than to MFB or RET stimuli. These anatomical distributions and functional properties of single cells may be useful in the unit analysis of the interrelated reinforcing, arousal and sensory properties of stimuli. The data support the proposition that intralaminar unit activity may play a role in integrating reward and pain mechanisms, with prolonged decreased and increased unit firing related to rewarding and aversive inputs respectively.

Modifications of sensory modality codes by stimuli of graded intensity in the cat thalamus

Recently it has been demonstrated that each sensory modality of lingual afferents elaborates its own pattern of spike activity. These patterns can be regarded as modality codes. The processing of such codes takes place only with high intensity stimulation. Therefore, the question arose as to how changes in the stimulus intensity influence the coding of afferent impulses. The method of study consisted of driving single thalamic neurons by applying square-wave pulses at 1/sec to the appropriate peripheral receptive field on the tongue and recording extracellular spike activity from neurons which relayed separately touch, pressure, thermal or gustatory modalities in the thalamus. Spikes which occured during 1000 consecutive post-stimulus periods were accumulated by superimposing the moment of stimulation in a digital computer. The accumulated counts per address were typed put by a read-out printer and were plotted on a dot-plotting autograph. Results indicated that stimulus intensity was frequency-coded within the initial burst of spike activity which followed any single stimulus. As the stimulation was intensified, the latency of the response decreased and the number of spikes which formed the first burst or cluster of activity increased. Spikes which formed the second and the third clusters did not elaborate a frequency code, although shifts in their latencies and changes in their range of scatter occured. Apparently, the first spike cluster in any of the four sensory codes process information about stimulus intensity, the late clusters pertain to modality coding. Some interaction between the frequency and modality codes does exist, however, suggesting the neural mechanism for observations regarding altered perception of stimulus quality with a change in stimulus intensity.