Pulmonary rapidly adapting receptors reflexly increase airway secretion in dogs

We attempted to determine whether stimulation of pulmonary rapidly adapting receptors (RARs) increase tracheal submucosal gland secretion in anesthetized open-chest dogs. Electroneurographic studies of pulmonary afferents established that RARs but not lung C-fibers were stimulated by intermittent lung collapse during deflation, collapse being produced by removing positive end-expiratory pressure (PEEP, 4 cmH2O) or by applying negative end-expiratory pressure (NEEP, -4 cmH2O). We measured tracheal secretion by the "hillocks" method. Removing PEEP or applying NEEP for 1 min increased secretion from a base line of 6.0 +/- 1.1 to 11.8 +/- 1.7 and 22.0 +/- 2.8 hillocks.cm-2.min-1, respectively (P less than 0.005). After PEEP was restored, dynamic lung compliance (Cdyn) was 37% below control, and secretion remained elevated (P less than 0.05). A decrease in Cdyn stimulates RARs but not other pulmonary afferents. Hyperinflation, which restored Cdyn and RAR activity to control, returned secretion rate to base line. Secretory responses to lung collapse were abolished by vagal cooling (6 degrees C), by pulmonary vagal section, or by atropine. We conclude that RAR stimulation reflexly increases airway secretion. We cannot exclude the possibility that reduced input from slowly adapting stretch receptors contributed to the secretory response.     

Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit

Campbell, Hillary, Krishnan Ravi, Emigdio Bravo, and C. Tissa Kappagoda. Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit. J. Appl.Physiol. 81(6): 2604-2610, 1996.The effects ofDiazinon PLUS aerosol on the activities of rapidly adapting receptors(RARs) and slowly adapting receptors (SAR) of the airways wereinvestigated in anesthetized rabbits. The effects on boththe baseline activity and the responses to stimulation by increasingmean left atrial pressure were examined. Action potentialswere recorded from the left cervical vagus nerve. Aerosols (particlesize 3 µm) were generated by a Mini-HEART nebulizer. We observed thatan aerosol of Diazinon PLUS (1:10 vol/vol dilution in normal saline)decreased the baseline RAR activity (n = 10) significantly (P < 0.05) from209 ± 77 to 120 ± 40 impulses/min. In the post-Diazinon PLUScontrol period, the RAR activity recovered partially to 185 ± 75 impulses/min and decreased significantly to 131 ± 52 impulses/min(P < 0.05) after a second exposureof Diazinon PLUS (undiluted) aerosol. Aerosols of normal saline in thecontrol state did not produce a significant change in the RAR activity.A group of SAR (n = 8) were examinedunder similar conditions, and it was found that only the exposure toDiazinon PLUS (undiluted) aerosol decreased the activity significantly (P < 0.05) from 1,536 ± 206 to1,367 ± 182 impulses/min. The effect of Diazinon PLUS on theresponse to increasing mean left atrial pressure was examined in sevenRARs. In the control state, RAR activity increased significantly(P < 0.05) during elevation of meanleft atrial pressure. This response was abolished after exposure toDiazinon PLUS. These findings suggest that diazinon may interfere withairway defense mechanisms by reducing the activity of RARs.

     

Stimulation of rapidly adapting pulmonary stretch receptors by pulmonary lymphatic obstruction in dogs

The effects of pulmonary lymphatic obstruction and pulmonary venous congestion on the activities of slowly adapting receptors (SAR) and rapidly adapting receptors (RAR) of the airways were examined in anaesthetized, artificially ventilated dogs. In 11 out of 12 RAR (12 dogs) examined, pulmonary lymphatic obstruction for a period of 20 min produced a sustained significant increase in activity without a significant change in peak airway pressure and dynamic compliance. The activity remained significantly elevated even after the pulmonary lymphatic obstruction was released. This stimulus was without effect on the SAR (n = 5 dogs). Pulmonary venous congestion alone increased the RAR activity (n = 7 dogs) significantly without producing significant changes in airway mechanics. Lymphatic obstruction, when superimposed upon congestion, did not produce a further significant increase in activity. In four dogs the effect of pulmonary venous congestion (left atrial pressure increased from 7.6 +/- 1.7 to 16.3 +/- 2.7 mmHg) (1 mmHg = 133.3 Pa) on pulmonary lymphatic flow was examined. The procedure caused a significant increase in lymph flow. These results suggest that in the dog, the RAR activity is influenced by changes in the pulmonary extravascular space.     

Stimulation of rapidly adapting receptors in canine lungs by a single breath of cigarette smoke

Inhalation of smoke generated from high-nicotine cigarettes frequently evoked an immediate augmented inspiration in conscious dogs (J. Appl. Physiol. 54: 562-570, 1983); this reflex response was believed to result from a stimulation of rapidly adapting receptors in the lungs. To test this hypothesis, we recorded the vagal afferent activity arising from the rapidly adapting receptors in the lungs and delivered 120 ml of high- and low-nicotine cigarette smoke separately in a single ventilatory cycle in 20 anesthetized open-chest and artificially ventilated dogs. These receptors were stimulated on the first breath of delivery of smoke generated by high-nicotine cigarettes; activity increased from a base line of 0.9 +/- 0.2 to a peak of 9.9 +/- 1.2 (SE) impulses/breath (n = 58). After three to six breaths when the receptors' discharge returned toward base-line activity, a delayed increase of activity emerged (peak activity = 3.4 +/- 0.6 impulses/breath, n = 58) in 32 of the 58 receptors studied and lasted for three to seven breaths. By contrast, only a mild stimulatory effect of low-nicotine cigarette smoke was found, either immediately or after a delay, in 15 of the 54 receptors studied. We conclude that rapidly adapting receptors are stimulated by a single breath of cigarette smoke and that nicotine is the primary stimulant agent.     

Exposing guinea pigs to ozone for 1wk enhances responsiveness of rapidly adapting receptors

Acute exposure to ozone causes changes inbreathing pattern and lung function which may be caused in part bystimulation of rapidly adapting receptors (RARs). The consequences ofrepeated daily ozone exposure on RAR responsiveness are unknown,although ozone-induced changes in pulmonary function diminish withrepeated exposure. Accordingly, we investigated whether repeated daily ozone exposure diminishes the general responsiveness of RARs. Guineapigs (n = 30) were exposed to 0.5 parts/million ozone or filtered air (8 h/day for 7 days). The animalswere then anesthetized, and RAR impulse activity, dynamic compliance(Cdyn), and lung resistance were recorded at baseline and in responseto four stimuli: substance P, methacholine, hyperinflation, and removalof positive end-expiratory pressure. Repeated daily ozone exposureexaggerated RAR responses to substance P, methacholine, andhyperinflation without causing physiologically relevant effects onbaseline or substance P- and methacholine-induced changes in Cdyn andlung resistance. Because agonist-evoked changes in RAR activitypreceded Cdyn changes, the data suggest that repeated daily ozoneexposure enhances RAR responsiveness via a mechanism other than changes in Cdyn.

     

Frequency responses of cat rapidly adapting mechanoreceptive fibers

The frequency responses of 11 rapidly adapting (RA) fibers in cat were studied by representing the average firing rate as a function of sinusoidal stimulus amplitude and stimulus frequency. Specifically, rate-intensity functions at different stimulation frequencies were fitted by four-parameter (a0, a1, a2, a3), piece-wise linear functions using nonlinear regression (n = 59; R2 > 0.877). Rate-intensity functions at intermediate frequencies were found by linear interpolation. The result of this analysis is rate-amplitude-frequency functions plotted as two-dimensional surfaces. The surfaces consist of five regions separated and sufficiently defined by four space curves. At 14 different frequencies, the statistical distribution of each rate-intensity-function parameter could be approximated by a particular lognormal distribution (n = 56; R2 > 0.796). The Kolmogorov-Smirnov test fails to reject this hypothesis for each combination of frequency and parameter (56 tests; p > 0.39). Therefore, at a given frequency, the variation of the parameters can be represented by lognormal distributions with specific means and standard deviations. Responses of six RA fibers, which are different from the data-set used for modeling, were compared with the stochastic model at different frequencies. The parameters of those fibers were tested against the null hypotheses that they were sampled from the particular parameter distributions dictated by the model. The Kolmogorov-Smirnov test fails to reject all the hypotheses at the alpha = 0.05 level (44 tests). At the alpha = 0.10 level, only a few test parameters were found to be departing from the model (a0 and a1 at 5 Hz; a2 at 20 Hz; a2 and a3 at 50 Hz). The remaining test parameters could be accurately described by the model. Having confirmed the validity of the model, the logarithmic means and the logarithmic standard deviations of the lognormally distributed rate-intensity-function parameters were estimated in the frequency range of 4-200 Hz. The rate-amplitude-frequency surfaces sampled from the established stochastic model completely characterize the rate responses of RA fibers to sinusoidal stimuli and are superior to tuning curves which require selecting criterion responses. The current rate-response model is promising for future computational work, especially on population modeling.     

Stability of rapidly adapting afferent entrainment vs responsivity

Spike discharge activity was recorded from low-threshold, rapidly adapting, skin mechanoreceptive afferents (RA afferents) dissected from the median (forelimb) or tibial (hindlimb) nerves in anesthetized monkeys and cats. The spike activity was evoked by delivery of controlled sinusoidal vertical skin displacement ("flutter") stimuli to the receptive field (RF). The stimuli (15-30 Hz; 30-400 mum peak-to-peak amplitude; duration 0.8-15 s) were superimposed on a static skin indentation (0.5-1.0 mm) which was either maintained continuously throughout the run or applied trial-by-trial. The neural activity and the analog signal of the position of the stimulator probe were digitized at 10 kHz resolution and stored for off-line analysis. The main goal was to determine whether changes in the RA afferent response to skin flutter stimulation may be responsible for the enhanced capacity to discriminate stimulus frequency that accompanies a relatively brief (approximately equal to 1 min) pre-exposure to such stimulation in humans. To this end, the spike train data were evaluated using methods that enabled independent measurement of entrainment and responsivity. Responsivity (response intensity) was measured as the average number of spikes/stimulus cycle, while entrainment (the degree to which evoked spike train activity is phase-locked to the stimulus) was quantitatively assessed using statistical techniques developed for the analysis of "circular" (directional) data, supplemented by methods based on the calculation of power spectra from point process data. The methods are demonstrated to enable quantification of RA afferent entrainment over a range of stimulus durations and amplitudes substantially greater than reported in previous studies. While RA afferent responsivity was found to decline to a minor extent (10-20%) both across and within stimulus trials, entrainment remained consistently high and stable, and exhibited no temporal trends or dependence on any other measured factor. The average phase angle of the entrained RA afferent response also remained stable both within and across trials, showing only a tendency to increase slightly during the initial 100-500 ms after stimulus onset. The results imply that the improved capacity to discriminate stimulus frequency that develops in response to an exposure to cutaneous flutter stimulation is not attributable to a change in RA afferent entrainment per se.     

Frequency responses of cat rapidly adapting mechanoreceptive fibers

The frequency responses of 11 rapidly adapting (RA) fibers in cat were studied by representing the average firing rate as a function of sinusoidal stimulus amplitude and stimulus frequency. Specifically, rate-intensity functions at different stimulation frequencies were fitted by four-parameter (a₀, a₁, a₂, a₃), piece-wise linear functions using nonlinear regression (n = 59; R² > 0.877). Rate-intensity functions at intermediate frequencies were found by linear interpolation. The result of this analysis is rate–amplitude–frequency functions plotted as two-dimensional surfaces. The surfaces consist of five regions separated and sufficiently defined by four space curves. At 14 different frequencies, the statistical distribution of each rate-intensity-function parameter could be approximated by a particular lognormal distribution (n = 56; R² > 0.796). The Kolmogorov–Smirnov test fails to reject this hypothesis for each combination of frequency and parameter (56 tests; p > 0.39). Therefore, at a given frequency, the variation of the parameters can be represented by lognormal distributions with specific means and standard deviations. Responses of six RA fibers, which are different from the data-set used for modeling, were compared with the stochastic model at different frequencies. The parameters of those fibers were tested against the null hypotheses that they were sampled from the particular parameter distributions dictated by the model. The Kolmogorov–Smirnov test fails to reject all the hypotheses at the α = 0.05 level (44 tests). At the α = 0.10 level, only a few test parameters were found to be departing from the model (a₀ and a₁ at 5?Hz; a₂ at 20?Hz; a₂ and a₃ at 50?Hz). The remaining test parameters could be accurately described by the model. Having confirmed the validity of the model, the logarithmic means and the logarithmic standard deviations of the lognormally distributed rate-intensity-function parameters were estimated in the frequency range of 4–200?Hz. The rate–amplitude–frequency surfaces sampled from the established stochastic model completely characterize the rate responses of RA fibers to sinusoidal stimuli and are superior to tuning curves which require selecting criterion responses. The current rate-response model is promising for future computational work, especially on population modeling.     

Stability of rapidly adapting afferent entrainment vs responsivity

Spike discharge activity was recorded from low-threshold, rapidly adapting, skin mechanoreceptive afferents (RA afferents) dissected from the median (forelimb) or tibial (hindlimb) nerves in anesthetized monkeys and cats. The spike activity was evoked by delivery of controlled sinusoidal vertical skin displacement ("flutter") stimuli to the receptive field (RF). The stimuli (15-30 Hz; 30-400 microm peak-to-peak amplitude; duration 0.8-15 s) were superimposed on a static skin indentation (0.5-1.0 mm) which was either maintained continuously throughout the run or applied trial-by-trial. The neural activity and the analog signal of the position of the stimulator probe were digitized at 10 kHz resolution and stored for off-line analysis. The main goal was to determine whether changes in the RA afferent response to skin flutter stimulation may be responsible for the enhanced capacity to discriminate stimulus frequency that accompanies a relatively brief (approximately 1 min) pre-exposure to such stimulation in humans. To this end, the spike train data were evaluated using methods that enabled independent measurement of entrainment and responsivity. Responsivity (response intensity) was measured as the average number of spikes/stimulus cycle, while entrainment (the degree to which evoked spike train activity is phase-locked to the stimulus) was quantitatively assessed using statistical techniques developed for the analysis of "circular" (directional) data, supplemented by methods based on the calculation of power spectra from point process data. The methods are demonstrated to enable quantification of RA afferent entrainment over a range of stimulus durations and amplitudes substantially greater than reported in previous studies. While RA afferent responsivity was found to decline to a minor extent (10-20%) both across and within stimulus trials, entrainment remained consistently high and stable, and exhibited no temporal trends or dependence on any other measured factor. The average phase angle of the entrained RA afferent response also remained stable both within and across trials, showing only a tendency to increase slightly during the initial 100-500 ms after stimulus onset. The results imply that the improved capacity to discriminate stimulus frequency that develops in response to an exposure to cutaneous flutter stimulation is not attributable to a change in RA afferent entrainment per se.     

Distribution of the intensity-characteristic parameters of cat rapidly adapting mechanoreceptive fibers

Modeling population responses of nerve fibers requires statistical characterization of fiber-response properties. The rate/intensity characteristics of cat rapidly adapting (RA) fibers were fitted by four-parameter, piece-wise linear functions using nonlinear regression (n = 14; R2 > 0.958). The parameters were tested against the null hypothesis that they are log normally distributed. The test fail to reject this hypothesis (Kolmogorov-Smirnov p>0.477). However, a significant statistical difference was found between the specific lognormal distributions obtained from monkey (Johnson, J Neurophysiol 37: 48-72, 1974) and cat for all four parameters (Kolmogorov-Smirnov, p<0.0075, p<0.05, p<0.0001, p<0.00007). Although the stimulus contactor size was not the same in monkey and cat studies, the differences between monkey and cat fibers are attributed to anatomical differences in the glabrous sin of both species. Modeling studies suggest that the absolute firing thresholds of RA fibers have a right-skewed distribution because of the anatomical constraints present in both species' skin. Meissner corpuscles, which are the sensory end-organs of RA fibers, are likely to be found deeper in the skin within dermal papilla, therefore, the thresholds can be elevated. However, the thresholds are bounded at lower end, probably due to the epidermal junction that acts as a superficial mechanical barrier for these corpuscles.     

Short-term memory trace in rapidly adapting synapses of inferior temporal cortex

Visual short-term memory tasks depend upon both the inferior temporal cortex (ITC) and the prefrontal cortex (PFC). Activity in some neurons persists after the first (sample) stimulus is shown. This delay-period activity has been proposed as an important mechanism for working memory. In ITC neurons, intervening (nonmatching) stimuli wipe out the delay-period activity; hence, the role of ITC in memory must depend upon a different mechanism. Here, we look for a possible mechanism by contrasting memory effects in two architectonically different parts of ITC: area TE and the perirhinal cortex. We found that a large proportion (80%) of stimulus-selective neurons in area TE of macaque ITCs exhibit a memory effect during the stimulus interval. During a sequential delayed matching-to-sample task (DMS), the noise in the neuronal response to the test image was correlated with the noise in the neuronal response to the sample image. Neurons in perirhinal cortex did not show this correlation. These results led us to hypothesize that area TE contributes to short-term memory by acting as a matched filter. When the sample image appears, each TE neuron captures a static copy of its inputs by rapidly adjusting its synaptic weights to match the strength of their individual inputs. Input signals from subsequent images are multiplied by those synaptic weights, thereby computing a measure of the correlation between the past and present inputs. The total activity in area TE is sufficient to quantify the similarity between the two images. This matched filter theory provides an explanation of what is remembered, where the trace is stored, and how comparison is done across time, all without requiring delay period activity. Simulations of a matched filter model match the experimental results, suggesting that area TE neurons store a synaptic memory trace during short-term visual memory.     

Asymmetric response properties of rapidly adapting mechanoreceptive fibers in the rat glabrous skin

Previous histological and neurophysiological studies have shown that the innervation density of rapidly adapting (RA) mechanoreceptive fibers increases towards the fingertip. Since the psychophysical detection threshold depends on the contribution of several RA fibers, a high innervation density would imply lower thresholds. However, our previous human study showed that psychophysical detection thresholds for the Non-Pacinian I channel mediated by RA fibers do not improve towards the fingertip. By recording single-unit spike activity from rat RA fibers, here we tested the hypothesis that the responsiveness of RA fibers is asymmetric in the proximo-distal axis which may counterbalance the effects of innervation density. RA fibers (n?=?32) innervating the digital glabrous skin of rat hind paw were stimulated with 40-Hz sinusoidal mechanical bursts at five different stimulus locations relative to the receptive field (RF) center (two distal, one RF center, two proximal). Different contactor sizes (area: 0.39, 1.63, 2.96?mm²) were used. Rate-intensity functions were constructed based on average firing rates, and the absolute spike threshold and the entrainment threshold were obtained for each RA fiber. Thresholds for proximal stimulus locations were found to be significantly higher than those for distal stimulus locations, which suggests that the mechanical stimulus is transmitted better towards the proximal direction. The effect of contactor size was not significant. Mechanical impedance of the rat digital glabrous skin was further measured and a lumped-parameter model was proposed to interpret the relationship between the asymmetric response properties of RA fibers and the mechanical properties of the skin.