Sensory Innervation of the Raccoon Forepaw: 1. Receptor Types in Glabrous and Hairy Skin and Deep Tissue

Electrophysiological recordings were made from the median, ulnar, radial, and dorsal ulnar nerves to determine the types of mechanosensory receptors serving glabrous and hairy skin surfaces of the raccoon forepaw. In addition to the cutaneous mechanoreceptors, fibers innervating deep tissues were also recorded from each of these nerves. These included sensory fibers innervating muscles, joints, claws, and the subcutaneous pulp.

The array of receptors serving raccoon glabrous skin was the same as found in monkeys and humans: Rapidly adapting (RA), slowly adapting (SA), and Pacinian (Pc) fibers were characterized. Pacinian fibers have been rarely described in previous physiological studies of the raccoon peripheral nerves, but in the present study they composed between 14% and 18% of the glabrous skin mechanoreceptors recorded. A distal-proximal gradient in the density of skin innervation was evident for all three types of receptors.

Receptors characterized in the hairy skin of the dorsal paw were similar to those described in other mammals, and included both down and guard hair afferents, non-hair-associated RA fibers, and SA I and SA II fibers. The relative proportions of these fibers differed from those generally reported for the hairy skin of other mammals. SA hair-associated afferent fibers, which have been reported previously only in primate hairy skin, were also found in large numbers in the raccoon. Similarities and differences in the frequency and types of receptors innervating the raccoon forepaw, the forepaws of other mammals, and the hands of primates (including humans) are discussed.     

Central pathways of pulmonary and lower airway vagal afferents.

Lung sensory receptors with afferent fibers coursing in the vagus nerves are broadly divided into three groups: slowly (SAR) and rapidly (RAR) adapting stretch receptors and bronchopulmonary C fibers. Central terminations of each group are found in largely nonoverlapping regions of the caudal half of the nucleus of the solitary tract (NTS). Second order neurons in the pathways from these receptors innervate neurons located in respiratory-related regions of the medulla, pons, and spinal cord. The relative ease of selective activation of SARs, and to a lesser extent RARs, has allowed for more complete physiological and morphological characterization of the second and higher order neurons in these pathways than for C fibers. A subset of NTS neurons receiving afferent input from SARs (termed pump or P-cells) mediates the Breuer-Hering reflex and inhibits neurons receiving afferent input from RARs. P-cells and second order neurons in the RAR pathway also provide inputs to regions of the ventrolateral medulla involved in control of respiratory motor pattern, i.e., regions containing a predominance of bulbospinal premotor neurons, as well as regions containing respiratory rhythm-generating neurons. Axon collaterals from both P-cells and RAR interneurons, and likely from NTS interneurons in the C-fiber pathway, project to the parabrachial pontine region where they may contribute to plasticity in respiratory control and integration of respiratory control with other systems, including those that provide for voluntary control of breathing, sleep-wake behavior, and emotions.     

Two types of P neurons in the medullary dorsal respiratory cellular group in cats

Electrophysiological properties of P neurons localized in the medullary dorsal respiratory cellular group and of vagal afferent fibers innervating these neurons were studied in acute experiments on nembutal-anesthetized cats with preserved spontaneous respiration. P neurons were shown to form a non-homogeneous cellular population. They generated phasic discharges during the whole inspiration period, but differed in their responses to lung inflation. These findings allowed us to classify P neurons as slowly adapting and rapidly adapting units, probably activated by slowly and rapidly adapting pulmonary receptors, respectively. Sensitivity of the slowly adapting P neurons to activation by the corresponding receptors and the mechanisms underlying the participation of the two types of P neurons in the reflex feedback between the respiratory center and lungs are discussed.Neirofiziologiya/Neurophysiology, Vol. 26, No. 3, pp. 211–217, May–June, 1994.     

Spinal dorsal column afferent fiber composition in the pigeon: an electrophysiological investigation

Summary The spinal dorsal column of homing pigeons (Colomba livia) was investigated electrophysiologically by recording responses from individual afferent fibers at a high cervical level (segments C4-C5) to mechanical stimulation of wing skin and deep tissue. Of 157 afferent fibers 134 were cutaneous afferents. The remainder were afferents of deep receptors.Thirty of the cutaneous afferents were slowly adapting and 87 rapidly adapting (17 not identified). Rapidly adapting afferents were studied with regard to Pacinianlike characteristics (Herbst corpuscles in birds; vibration sensitive receptors). Of 43 rapidly adapting afferents 38 were classified as afferents of vibration sensitive Herbst corpuscles and 5 as non vibration sensitive rapidly adapting afferents; 44 afferents could not be studied sufficiently with regard to vibrational stimuli. The vibration sensitive Herbst corpuscle afferents had U-shaped vibrational tuning curves and responded best to vibration frequencies of 300 to 400 Hz. The 11 threshold for 300 Hz vibration ranged from 2 to 36 um. Herbst corpuscle afferents always showed strong phase coupling to the stimulus cycle.Afferents of deep receptors showed slowly adapting responses to firm pressure or movements of limbs and were classified as joint receptors. No muscle spindle afferents were encountered.Primary afferent fibers were identified in 89 cases (80 cutaneous and 9 deep), postsynaptic elements in 15 cases (11 cutaneous, 4 deep). Only slowly adapting responses were found in postsynaptic fibers.Abbreviations CV coefficient of variation - EI entrainment index - INTH interval histogram - PSTH peristimulus time histogram - RA rapidly adapting - SA slowly adapting     

Stretch receptors of the lungs in the frog Rana temporaria

In experiments on isolated lungs, studies have been made on the activity of single afferent fibers during simulated expiration and inspiration. Both slowly adapting and rapidly adapting voluminous stretch receptors were found in the frog lungs. The latter type exhibits the activity also during fast simulated expiration. Using acetylcholine and histamine, it was shown that the level of excitability of the receptors investigated depends on functional condition of the plain muscles in the pulmonary wall.     

Reflexes from the lungs and airways: historical perspective.

Historical aspects of respiratory reflexes from the lungs and airways are reviewed, up until about 10 yr ago. For most of the 19th century, the possible reflex inputs into the "respiratory center," the position of which had been identified, were very speculative. There was little concept of reflex control of the pattern of breathing. Then, in 1868, Breuer published his paper on "The self-steering of respiration via the Nervus Vagus." For the first time this established the role of vagal inflation and deflation reflexes in determining the pattern of breathing. Head later extended Breuer's work, and Kratschmer laid a similar basis for reflexes from the nose and larynx. Then, 50-60 yr later, the development of the thermionic valve and the oscilloscope allowed recording action potentials from single nerve fibers in the vagus. In 1933, Adrian showed that slowly adapting pulmonary stretch receptors were responsible for the inflation reflex. Later, Knowlton and Larrabee described rapidly adapting receptors and showed that they mediated deep augmented breaths and the deflation reflex. Still later, it was established that rapidly adapting receptors were, at least in part, responsible for cough. In 1954, Paintal began his study of C-fiber receptors (J receptors), work greatly extended by the Coleridges. Since approximately 10 yr ago, when the field of this review stops, there has been an explosion of research on lung and airway receptors, many aspects of which are dealt with in other papers in this series.     

Receptor sites for alanine,proline, and betaine in the palatal taste system of the puffer,Fugu pardalis

Summary To elucidate the relative independence of the receptor sites for amino acids and betaine in the gustatory system of fish, the neural responses from the ramus palatinus facialis innervating the anterior palate of the puffer, Fugu pardalis, were recorded.There were observed independent amino acidsensitive and betaine-sensitive fibers.Cross-adaptation to pairs of stimulant was studied. The pair stimulants were applied reciprocally, i.e. after adapting with one stimulus the second stimulus was applied and then reversed. There were observed 3 types of cross-effects for the pairs of stimulants tested: (1) a reciprocal profound cross-adaptation; (2) no distinct cross-adaptation; and (3) a reciprocal enhancement of the response between betaine and alanine or glycine. Such an enhancement between betaine and alanine occurred in the amino acid-sensitive fibers, suggesting that betaine has an enhancing effect on the amino acid receptors.The present results suggest at least 3 different groups of receptor sites for the stimulants tested: (1) alanine sites for alanine, glycine and sarcosine; (2) proline sites for proline and dimethylglycine; and (3) betaine sites for betaine and dimethylglycine.     

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.     

The origin of slow potentials on the tongue surface induced by frog glossopharyngeal efferent fiber stimulation

When the glossopharyngeal (GP) nerve of the frog was stimulated electrically, electropositive slow potentials were recorded from the tongue surface and depolarizing slow potentials from taste cells in the fungiform papillae. The amplitude of the slow potentials was stimulus strength- and the frequency-dependent. Generation of the slow potentials was not related to antidromic activity of myelinated afferent fibers in the GP nerve, but to orthodromic activity of autonomic post-ganglionic C fibers in the GP nerve. Intravenous injection of atropine abolished the positive and depolarizing slow potentials evoked by GP nerve stimulation, suggesting that the slow potentials were induced by the activity of parasympathetic post-ganglionic fibers. The amplitude and polarity of the slow potentials depended on the concentration of adapting NaCl solutions applied to the tongue surface. These results suggest that the slow potentials recorded from the tongue surface and taste cells are due to the liquid junction potential generated between saliva secreted from the lingual glands by GP nerve stimulation and the adapting solution on the tongue surface.     

Activation of lung vagal sensory receptors by circulatory endotoxin in rats

Although endotoxin is known to induce various pulmonary responses that are linked to the function of lung vagal sensory receptors, its effects on these pulmonary receptors are still not clear. This study investigated the effects of circulatory endotoxin on the afferent activity of lung vagal sensory receptors in rats. We recorded afferent activity arising from vagal pulmonary C fibers (CFs), rapidly adapting receptors (RARs), tonic pulmonary stretch receptors (T-PSRs), and phasic pulmonary stretch receptors (P-PSRs) in 64 anesthetized, paralyzed, and artificially ventilated rats. Intravenous injection of endotoxin (50 mg/kg; lipopolysaccharide) stimulated 7 of the 8 CFs, 8 of the 8 RARs, and 4 of the 8 T-PSRs studied, while having no effect on the 8 P-PSRs tested. The stimulation started 3-16 min after endotoxin injection and lasted until the end of the 90-min observation period. The evoked discharge of either CFs or RARs was not in phase with the ventilatory cycle, whereas that of T-PSRs showed a respiratory modulation. Injection of a saline vehicle caused no significant change in the discharge of these receptors. Additionally, endotoxin significantly produced an increase in total lung resistance, and decreases in dynamic lung compliance and arterial blood pressure. Our results demonstrate that a majority of lung vagal sensory receptors are activated following intravenous injection of endotoxin, and support the notion that these pulmonary receptors may function as an important afferent system during endotoxemia.     

Multireceptor activation of the pulmonary chemoreflex

Schertel et al. (J. Appl. Physiol. 61: 1237-1240, 1984) reported that pulmonary C fibers initiate the prompt apnea followed by rapid shallow breathing evoked by pulmonary arterial injections of capsaicin. However, doubt has remained as to whether these changes in breathing pattern are induced exclusively by direct stimulation of pulmonary C fibers or whether secondary stimulation of slowly adapting pulmonary stretch receptors by capsaicin-induced reflex bronchoconstriction also contributes to the response. To determine the contribution of this secondary mechanism to changes in breathing pattern, we evoked the pulmonary chemoreflex in spontaneously breathing dogs before and after blockade of muscarinic receptors with atropine. Right atrial injections of capsaicin before the administration of atropine induced a classical pulmonary chemoreflex, i.e., apnea, hypotension, and bradycardia followed by rapid shallow breathing and bronchoconstriction. After atropine, all components of the pulmonary chemoreflex induced by right atrial injections of capsaicin remained intact except bronchoconstriction. However, the absolute magnitude of the change in each component of the reflex except apnea was significantly attenuated. We conclude that the classic pulmonary chemoreflex is a complex phenomenon initiated primarily by stimulation of pulmonary C fibers but significantly influenced by secondary stimulation of slowly adapting pulmonary stretch receptors.     

Spectrum of myelinated pulmonary afferents

Myelinated pulmonary afferents are classified as rapidly adapting receptors (RARs) or slowly adapting receptors (SARs) by their adaptation rate. Behavior of SARs varies greatly, and therefore the present study tries to further categorize SARs according to their mechanical properties. Single-fiber activity of 104 SARs was examined in anesthetized, open-chest, artificially ventilated rabbits. According to the increase or decrease in activity during removal of positive-end-expiratory pressure (PEEP), SARs were divided into two groups. In one group mean activity increased from 31 +/- 6 to 46 +/- 7 impulses per second (imp/s; n = 11); in another group mean activity decreased from 44 +/- 2 to 25 +/- 1 imp/s (n = 93). The first group of SARs has high adaptation indexes (RAR-like), which increased with inflation pressure (36 +/- 3, 44 +/- 3, and 47 +/- 3% for 10, 15, and 20 cmH(2)O, respectively; P < 0.005). Their peak activity shifted from inflation phase to deflation phase during PEEP removal. The second group of SARs has low-adaptation indexes (typical SARs), which were not affected by inflation pressure (19 +/- 1, 18 +/- 1, and 17 +/- 1% for 10, 15, and 20 cmH(2)O; P = 0. 516). Their peak activity did not shift during PEEP removal. Because there are overlaps in other characteristics, it is proposed that myelinated vagal afferents are viewed as a heterogeneous group; their behaviors are like a spectrum, where typical RARs and SARs represent two extremes of the spectrum. The receptor behavior might be determined by anatomic location and its environment.     

Sensory Innervation of the Raccoon Forepaw: 2. Response Properties and Classification of Slowly Adapting Fibers

Physiological recordings were made from 136 slowly adapting (SA) fibers in the median and ulnar nerves that innervate the glabrous skin of the raccoon. It was found that wetting the skin produced large increases in fiber responsiveness and decreases in threshold. Their responses decreased rapidly with slight displacements of the stimulus away from the center of the receptive field. Responses also decreased with increases in the diameter of the tip of the stimulus probe. The length of time that an SA fiber responded to a prolonged indentation was related to the magnitude of the indentation, and was greater after wetting of the skin. The absence of any clear and consistent grouping of fibers into moderately SA (MSA) and very SA (VSA) units argues against the existence of two types of SA receptors differing in this property. However, the distinction between SA I and SA II fibers that has been made in other species was confirmed in the raccoon.     

The frequency selectivity of information-processing channels in the tactile sensory system

The frequency selectivity of the P, NP I, and NP II channels of the four-channel model of mechanoreception for glabrous skin was measured psychophysically by an adaptation tuning curve procedure. The results substantially extend the frequency range over which the frequency selectivity of these channels is known and further confirm the hypothesis that the input stage of each of these channels consists of specific sensory nerve fibers and associated receptors. Specifically, the frequency characteristics of Pacinian nerve fibers, rapidly adapting (RA) nerve fibers, and slowly adapting Type II (SA II) nerve fibers were found to be the peripheral neurophysiological correlates of the P, NP I, and NP II channels, respectively. The finding that the tuning characteristic for a test stimulus of 250 Hz delivered through a small (0.008 cm2) contactor depended dramatically on the duration of the test stimulus whereas the detection threshold did not, provides new evidence in support of the hypothesis that separate NP II and P channels exist.     

Book Review

Mechanosensory activity was recorded extracellularly from branches of the internal pedal nerve in the femur of the horseshoe crab walking leg. The receptors appeared to be associated with the tibial flexor muscles and generally showed little spontaneous activity in the isolated leg. Sensory activity was most easily and reliably elicited by active flexor contraction against a load, and it did not require joint movement. The neurons responsible for this activity appear to be true series tension receptors. Since such cells are likely to be adequately stimulated only by tension developed in muscle fibers with which they are in series, whole muscle tension is not always directly related to the activity of a given receptor. In order to estimate the magnitude of the force at a receptor under study various indirect methods of altering the tension in and spatial relationships between the fibres of a single muscle were employed. These include active stimulation while (a) fixing the muscle at various lengths (joint angles), (b) lengthening or shortening the muscle passively over a wide range and at varying rates. The results obtained are consistent with the suggestion that the sensory cells are series tension receptors.     

Modality of the bush-like receptors

In an isolated preparation of the Rana temporaria urinary bladder after a simultaneous morphological and physiological investigation a, structural-functional differentiation of free bushy receptors has been demonstrated. According to arborization character and to the appearance of deferent fibers, the receptors are divided into two types. The first type receptors have a simple structure, a long deferent poorly branching myelin fiber, terminating in a diffuse bush near blood vessels. The second type receptors are of a more complex structure. Their myelin fibers, when leaving the fasciculus, are 4-8 times shorter than the first type receptors, undergo dichotomic and trichotomic divisions several times, and in their distal part they form two initial myelin segments. Their receptory apparatus has a tree-like bush-shaped form and consists of several compact bushes. The impulse activity of the receptors is also characterized by two types of action potentials, differing in their amplitude. When responding to a mechanical stimulation, the high voltage impulse frequency changes, when sodium chloride concentration is increased, the low voltage impulse frequency changes. There is a certain localization of the zones in the preparation from which it is possible to obtain predominantly either low voltage or high voltage responses. The response to the low voltage reaction proves to be obtained from the first type receptors, and that to the high voltage reaction--from the second type receptors. Thus, in the frog, that is on a low phylogenetic stage, differentiation of the free bushy sensitive terminal into mechano- and chemoreceptors is already outlined.     

Cutaneous sensory afferents recorded from the nervus intramandibularis ofGallus gallus vardomesticus

Summary The responses of single sensory afferent nerve fibres were recorded from small nerve bundles of the intramandibular nerve of the chicken following thermal and mechanical stimulation of the beak. Thermoreceptors, nociceptors and mechanoreceptors were identified and their responses characterized.Of the thermoreceptors identified 11 units were classified as cold receptors, which responded to cooling the receptive field by increasing the discharge rate and had conduction velocities in the range 0.83 to 4.4 m/s. Only one warm unit was identified.Two classes of nociceptors were identified: mechano-thermal (polymodal) nociceptors and high threshold mechanical nociceptors. The discharge characteristics and stimulus-response curves of both types were described. While the mechanothermal nociceptors were exclusively C-fibres (c.v. 0.4 to 1.86 m/s), the high threshold mechanoreceptors contained both C and A delta fibres (c.v. 1 to 5.5 m/s). Thermal response thresholds for the mechano-thermal units ranged from 41 to 50 °C with mechanical thresholds of 2 to over 50 g. Mechanical thresholds for the high threshold units ranged from 5 to over 50 g.The mechanoreceptors were either slowly or rapidly adapting. The pattern of response together with stimulus-response curves were presented for the slowly adapting units. Conduction velocities of the slowly adapting units varied from 0.7 to 20 m/s and mechanical threshold from 0.1 to 2 g. On the basis of their response to a vibrating, and a ramp-and-hold mechanical stimulus, the rapidly adapting units were divided into Herbst and Grandry units with only the Herbst units responding accurately to the vibrating stimulus. Both units had fibres conducting in the 50 m/s range with thresholds in the 0.1 to 10 g range.The results are discussed in relation to the receptors found in other avian species and mammalian peripheral sensory afferents.Abbreviations c.v. conduction velocity - RA rapidly adapting (receptors) - SA slowly adapting (receptors)     

The frequency selectivity of information-processing channels in the tactile sensory system

The frequency selectivity of the P, NP I, and NP II channels of the four-channel model of mechanoreception for glabrous skin was measured psychophysically by an adaptation tuning curve procedure. The results substantially extend the frequency range over which the frequency selectivity of these channels is known and further confirm the hypothesis that the input stage of each of these channels consists of specific sensory nerve fibers and associated receptors. Specifically, the frequency characteristics of Pacinian nerve fibers, rapidly adapting (RA) nerve fibers, and slowly adapting Type II (SA II) nerve fibers were found to be the peripheral neurophysiological correlates of the P, NP I, and NP II channels, respectively. The finding that the tuning characteristic for a test stimulus of 250 Hz delivered through a small (0.008 cm²) contactor depended dramatically on the duration of the test stimulus whereas the detection threshold did not, provides new evidence in support of the hypothesis that separate NP II and P channels exist.     

Effect of GABA(B) receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon

Spinal afferents innervating the gastrointestinal tract are the major pathways for visceral nociception. Many centrally acting analgesic drugs attenuate responses of visceral primary afferent fibers by acting at the peripheral site. Gamma-amino butyric acid (GABA), a major inhibitory neurotransmitter, acts via metobotropic GABA(B) and ionotropic GABA(A)/GABA(C) receptors. The aim of this study was to test the peripheral effect of selective GABA(B) receptor agonist baclofen on responses of the pelvic nerve afferent fibers innervating the colon of the rat. Distension-sensitive pelvic nerve afferent fibers were recorded from the S(1) sacral dorsal root in anesthetized rats. The effect of baclofen (1-300 micromol/kg) was tested on responses of these fibers to colorectal distension (CRD; 60 mmHg, 30 s). A total of 21 pelvic nerve afferent fibers was recorded. Mechanosensitive properties of four fibers were also recorded before and after bilateral transections of T(12)-S(3) ventral roots (VR). Effect of baclofen was tested on 15 fibers (7 in intact rats, 4 in rats with transected VR, and 4 in rats pretreated with CGP 54626). In nine fibers (5/7 in intact and 4/4 in VR transected rats), baclofen produced dose-dependent inhibition of response to CRD. Pretreatment with selective GABA(B) receptor antagonist CGP 54626 (1 micromol/kg) reversed the inhibitory effect of baclofen. Results suggest a peripheral role of GABA(B) receptors in the inhibition of mechanotransduction property of distension-sensitive pelvic nerve afferent fibers.     

Responses of pulmonary vagal mechanoreceptors to high-frequency oscillatory ventilation

The discharge of 57 slowly adapting pulmonary stretch receptors (PSR's) and 16 rapidly adapting receptors (RAR's) was recorded from thin vagal filaments in anesthetized dogs. The receptors were localized and separated into three groups: extrathoracic tracheal, intrathoracic tracheal, and intrapulmonary receptors. The influence of high-frequency oscillatory ventilation (HFO) at 29 Hz on receptor discharge was analyzed by separating the response to the associated shift in functional residual capacity (FRC) from the oscillatory component of the response. PSR activity during HFO was increased from spontaneous breathing (49%) and from the static FRC shift (25%). PSR activity during the static inflation was increased 19% over spontaneous breathing. RAR activity was also increased with HFO. These results demonstrate that 1) the increased activity of PSR and RAR during HFO is due primarily to the oscillating action of the ventilator and secondarily to the shift in FRC associated with HFO, 2) the increased PSR activity during HFO may account for the observed apneic response, and 3) PSR response generally decreases with increasing distance from the tracheal opening.