Rapidly Adapting Mechanoreceptors Research Articles

Piezo2 voltage-block regulates mechanical pain sensitivity.

PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurones in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available for opening by mechanical force. Conversely, most PIEZO2 channels are blocked at normal negative resting membrane potentials. The physiological function of this unusual biophysical property of PIEZO2 channels, however, remained unknown. We characterized the biophysical properties of three PIEZO2 ion channel mutations at an evolutionarily conserved Arginine (R2756). Using genome engineering in mice we generated Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice to characterize the physiological consequences of altering PIEZO2 voltage sensitivity in vivo. We measured endogenous mechanosensitive currents in sensory neurones isolated from the dorsal root ganglia and characterized mechanoreceptor and nociceptor function using electrophysiology. Mice were also assessed behaviourally and morphologically. Mutations at the conserved Arginine (R2756) dramatically changed the biophysical properties of the channel relieving voltage block and lowering mechanical thresholds for channel activation. Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice that were homozygous for gain of function mutations were viable and were tested for sensory changes. Surprisingly, mechanosensitive currents in nociceptors, neurones that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but mechanosensitive currents in most mechanoreceptors that underlie touch sensation were only mildly affected by the same mutations. Single-unit electrophysiological recordings from sensory neurones innervating the glabrous skin revealed that rapidly-adapting mechanoreceptors that innervate Meissner's corpuscles exhibited slightly decreased mechanical thresholds in Piezo2 knock-in mice. Consistent with measurements of mechanically activated currents in isolated sensory neurones essentially all cutaneous nociceptors, both fast conducting Aδ-mechanonociceptors and unmyelinated C-fibre nociceptors were substantially more sensitive to mechanical stimuli and indeed acquired receptor properties similar to ultrasensitive touch receptors in Piezo2 knock-in mice. Mechanical stimuli also induced enhanced ongoing activity in cutaneous nociceptors in Piezo2 knock-in mice and hyper-sensitive PIEZO2 channels were sufficient alone to drive ongoing activity, even in isolated nociceptive neurones. Consistently, Piezo2 knock-in mice showed substantial behaviourally hypersensitivity to noxious mechanical stimuli. Our data indicate that ongoing activity and sensitization of nociceptors, phenomena commonly found in human chronic pain syndromes, can be driven by relieving the voltage-block of PIEZO2 ion channels. Indeed, membrane depolarization caused by multiple noxious stimuli may sensitize nociceptors by relieving voltage-block of PIEZO2 channels.

Pressure-clamped single-fiber recording technique: A new recording method for studying sensory receptors.

An electrophysiological technique that can record nerve impulses from a single nerve fiber is indispensable for studying modality-specific sensory receptors such as low threshold mechanoreceptors, thermal receptors, and nociceptors. The teased-fiber single-unit recording technique has long been used to resolve impulses that are likely to be from a single nerve fiber. The teased-fiber single-unit recording technique involves tedious nerve separation procedures, causes nerve fiber impairment, and is not a true single-fiber recording method. In the present study, we describe a new and true single-fiber recording technique, the pressure-clamped single-fiber recording method. We have applied this recording technique to mouse whisker hair follicle preparations with attached whisker afferents as well as to skin-nerve preparations made from mouse hindpaw skin and saphenous nerves. This new approach can record impulses from rapidly adapting mechanoreceptors (RA), slowly adapting type 1 mechanoreceptors (SA1), and slowly adapting type 2 mechanoreceptors (SA2) in these tissue preparations. We have also applied the pressure-clamped single-fiber recordings to record impulses on Aβ-fibers, Aδ-fibers, and C-fibers. The pressure-clamped single-fiber recording technique provides a new tool for sensory physiology and pain research.

Functional properties of mechanoreceptors in mouse whisker hair follicles determined by the pressure-clamped single-fiber recording technique

Several types of mechanoreceptors have been identified anatomically in rodent whisker hair follicles, but their functional properties have not been fully studied. Here we developed a pressure-clamped single-fiber recording technique to record impulses on mouse whisker hair follicle afferent nerves following displacements of whisker hair follicles. On the basis of the patterns of impulses evoked by the mechanical stimulation, three functional types of mechanoreceptors were identified, including rapidly adapting (RA), slowly adapting type 1 (SA1), and slowly adapting type 2 (SA2) mechanoreceptors. Impulses of all these mechanoreceptors were almost completely abolished by 30 nM TTX, and were largely suppressed by cooling temperatures at 15°C. Tested at different displacement distances as different stimulation intensity, RA mechanoreceptors showed a limited capacity for stimulation intensity encoding, but both SA1 and SA2 mechanoreceptors displayed linear increases of impulse numbers with increased stimulation intensity. Tested with different ramp speed of displacements, RA impulses were only evoked by rapid ramp stimulation but SA1 and SA2 impulses could be evoked by both rapid and slow ramp stimulation. Tested with different stimulation frequency, all three types of mechanoreceptors well followed the stimulation at 10–100 Hz. Taken together, this study revealed some important functional properties of RA, SA1 and SA2 mechanoreceptors, which helps better understand the encoding of tactile information by different types of low-threshold mechanoreceptors.

Piezo2 Underlies Slowly-Inactivating Mechano-Current in Sensory Neurons from Tactile Specialist Birds

Mechano-gated ion channels are essential for the detection of touch by peripheral sensory neurons, but many aspects of touch physiology and mechanotransducer function remain obscure. Tactile specialist birds of the family Anatidae possess unique mechanosensory abilities with which they efficiently select edible matter in muddy water without visual or olfactory cues. Mechanical stimuli are transmitted by trigeminal mechanoreceptors innervating the bill, a highly specialized tactile organ. We show mechanosensory specialization in tactile, but not visually foraging birds involves the formation of functional rapidly-adapting mechanoreceptors that produce robust mechano-current via the Piezo2 channel with novel properties. Cloning and electrophysiological characterization of duck Piezo2 in a heterologous expression system shows that duck Piezo2 is functionally similar to the mouse orthologue, but with prolonged inactivation kinetics. We show that Piezo2 inactivation can be increased by co-expression with Tmem150C, a transmembrane protein that co-exists with Piezo2 in somatosensory neurons, suggesting a potential mechanism. Our results uncover possible evolutionary adaptations contributing to potentiation of mechanoreception in an organ-specific manner, and reveal the Piezo2 channel as a neuronal mechanotransducer with prolonged inactivation kinetics.

Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of Rapidly Adapting Mechanoreceptor Ascending Axons

Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of roof plate-derived radial glial-like cells (RGLCs) in the spinal cord dorsal column, which form a network of processes enriched with growth-promoting factors. In dreher mutant mice that lack RGLCs, the lengths of ascending RA mechanoreceptor axon branches are specifically reduced, whereas their descending and collateral branches, and other dorsal column and sensory pathways, are largely unaffected. Because the number and intrinsic growth ability of RA mechanoreceptors are normal in dreher mice, our data suggest that RGLCs provide critical non-cell autonomous growth support for the ascending axons of RA mechanoreceptors. Together, our work identifies a developmental mechanism specifically required for long-range spinal cord longitudinal axons.

Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors.

RET can be activated in cis or trans by its co-receptors and ligands in vitro, but the physiological roles of trans signaling are unclear. Rapidly adapting (RA) mechanoreceptors in dorsal root ganglia (DRGs) express Ret and the co-receptor Gfrα2 and depend on Ret for survival and central projection growth. Here, we show that Ret and Gfrα2 null mice display comparable early central projection deficits, but Gfrα2 null RA mechanoreceptors recover later. Loss of Gfrα1, the co-receptor implicated in activating RET in trans, causes no significant central projection or cell survival deficit, but Gfrα1;Gfrα2 double nulls phenocopy Ret nulls. Finally, we demonstrate that GFRα1 produced by neighboring DRG neurons activates RET in RA mechanoreceptors. Taken together, our results suggest that trans and cis RET signaling could function in the same developmental process and that the availability of both forms of activation likely enhances but not diversifies outcomes of RET signaling.

Stomatin‐domain protein interactions with acid‐sensing ion channels modulate nociceptor mechanosensitivity

Acid-sensing ion channels (ASICs) and their interaction partners of the stomatin family have all been implicated in sensory transduction. Single gene deletion of asic3, asic2, stomatin, or stoml3 all result in deficits in the mechanosensitivity of distinct cutaneous afferents in the mouse. Here, we generated asic3−/−:stomatin−/−, asic3−/−:stoml3−/− and asic2−/−:stomatin−/− double mutant mice to characterize the functional consequences of stomatin–ASIC protein interactions on sensory afferent mechanosensitivity. The absence of ASIC3 led to a clear increase in mechanosensitivity in rapidly adapting mechanoreceptors (RAMs) and a decrease in the mechanosensitivity in both Aδ- and C-fibre nociceptors. The increased mechanosensitivity of RAMs could be accounted for by a loss of adaptation which could be mimicked by local application of APETx2 a toxin that specifically blocks ASIC3. There is a substantial loss of mechanosensitivity in stoml3−/− mice in which ∼35% of the myelinated fibres lack a mechanosensitive receptive field and this phenotype was found to be identical in asic3−/−:stoml3−/− mutant mice. However, Aδ-nociceptors showed much reduced mechanosensitivity in asic3−/−:stoml3−/− mutant mice compared to asic3−/− controls. Interestingly, in asic2−/−:stomatin−/− mutant mice many Aδ-nociceptors completely lost their mechanosensitivity which was not observed in asic2−/− or stomatin−/− mice. Examination of stomatin−/−:stoml3−/− mutant mice indicated that a stomatin/STOML3 interaction is unlikely to account for the greater Aδ-nociceptor deficits in double mutant mice. A key finding from these studies is that the loss of stomatin or STOML3 in asic3−/− or asic2−/− mutant mice markedly exacerbates deficits in the mechanosensitivity of nociceptors without affecting mechanoreceptor function.

Acoustic emission measurement of rubbing and tapping contacts of skin and tongue surfaces in relation to tactile perception

The application of acoustic emission measurement (“acoustic tribology”) is explored for in vivo characterization of rubbing and tapping contacts of the biological tissues of skin and tongue. This acoustic signal originates from physical processes that are closely related to the rapid force fluctuations that are sensed by the rapidly-adapting mechanoreceptors involved in the sensation of touch. Demonstrated is the recording and analysis of sound produced by rubbing and tapping the skin against various surface textures of common materials and by rubbing the tongue against the palate or against food material in the mouth for 1 individual. The technique is shown to be sensitive to skin pre-treatment and pre-meals, and is also shown to discriminate between various surface textures and food materials in a way that relates to perception. The main advantages of the technique are its time-resolution, ease of operation and the fact that it is a direct in vivo measurement of processes that are closely related to texture perception.

Mice mechanoreceptors are modulated by Cav3.2 T‐type calcium channels

Mechanoreceptors are sensory receptors that respond to mechanical displacement and provide the senses of touch, pressure, vibration and proprioception. Mice have three types of low-threshold mechanoreceptors: slowly adapting mechanoreceptors (SAMs), rapidly adapting mechanoreceptors (RAMs) and D-hair receptors (Driscoll & Tavernarakis, 2000). D-hair receptors are the end-terminal of type Aδ fibre axons and present a high sensitivity and ultra-rapid temporal detection of slowly moving stimuli. The mRNA expression for the T-type voltage-gated calcium channel Cav3.2 is the only marker defined for mechanoreceptors and found almost exclusively in D-hair receptors. The Cav3.2 gene encodes one of the three low-voltage-activated (LVA) Ca2+ channels (Cav3.1, Cav3.2 and Cav3.3) and are all expressed by sensory neurons in the DRG (Iftinca et al. 2007). Previous published studies proposed that Cav3.2 channel has a primary role in nociception (Bourinet et al. 2005). However, another research group that used miberfradil, a drug that blocks all T-type channels, suggested that the mechanosensitivity of D-hair receptors is reduced by blockade of LVA channels (Shin et al. 2003). For this reason the specific physiological properties of the Cav3.2 channel has not been accurately described. In a recent issue of The Journal of Physiology, Wang & Lewin (2011) conducted a study with the purpose of demonstrating the role of the T-type Cav3.2 channels. In this study, Cav3.2−/− mutant mice were used to directly address the role of this channel in sensory transduction of cutaneous mechanoreceptors and nociceptors. Mice were produced by gene targeting in mouse ES cells; the targeting vector was designed to delete the IS5 region of the murine Cacna1H gene, which resulted in deletion of exon 6, corresponding to amino acid residues 216 to 267. This method was helpful in examining the mechanosensitivity of nociceptors and mechanoreceptors in normal Cav3.2 mice and in Cav3.2−/− mutant mice, proving that nociceptors sensitivity was not altered when the Cav3.2 gene was suppressed; on the other hand, D-hair receptor sensibility was drastically impaired in their ability to encode the properties of moving stimuli, losing their high sensitivity and ability to ensure rapid temporal detection to skin movement. In addition the functional properties of other mechanoreceptors and nociceptors were unaffected by the suppression of Cav3.2 channels. Why is this important? These new data provide conclusive results of the specific function of the T-type Cav3.2 channel, solving the previous controversy about its physiological function and proving that this specific gene is responsible for providing the functional and distinctive properties of D-hair receptors. Thus, this study encloses the specific activity of this gene, being now considered not only a high specific marker of D-hair receptors but also indispensable to maintain their high sensitivity in the detection of skin deflection. The expression of Cav3.2 in D-hair mechanoreceptors may serve to provide highly accurate temporal information about rapidly changing stimuli. This information helps humans to make fast and precise judgments about the speed and direction of tactile stimuli, a characteristic that can be considered vital for survival and functionality. This is the first time that the regulation for temporal coding in mouse mechanoreceptors from Cav3.2 T-type channels has been proved. Nevertheless, results from this study showed that there exists a possibility that a minor sub-population of nociceptors is dependent on the presence of Cav3.2 channels. The research revealed no certainty that such a population exists, and it is highly unlikely that this kind of population could be identified. Further studies will be needed to ascertain if this is indeed a possibility.

RETouching upon Mechanoreceptors

The rapidly adapting (RA) low-threshold mechanoreceptors respond to movement of the skin and vibration and are critical for the perception of texture and shape. In this issue of Neuron, two papers (Bourane et al. and Luo et al.) demonstrate that early-born Ret+ sensory neurons are RA mechanoreceptors, whose peripheral nerve terminals are associated with Meissner corpuscles, longitudinal lanceolate endings, and Pacinian corpuscles. The studies further show that Ret signaling is essential for the development of these mechanoreceptors.

The Human Thalamic Somatic Sensory Nucleus [Ventral Caudal (Vc)] Shows Neuronal Mechanoreceptor-Like Responses to Optimal Stimuli for Peripheral Mechanoreceptors

Although the response of human cutaneous mechanoreceptors to controlled stimuli is well studied, it is not clear how these peripheral signals may be reflected in neuronal activity of the human CNS. We now test the hypothesis that individual neurons in the human thalamic principal somatic sensory nucleus [ventral caudal (Vc)] respond selectively to the optimal stimulus for one of the four mechanoreceptors. The optimal stimuli for particular mechanoreceptors were defined as follows: Pacinian corpuscles (PC), vibration at 128 Hz; rapidly adapting (RA), vibration at 32 or 64 Hz; slowly adapting type 1 (SA1), edge; slowly adapting type 2 (SA2), skin stretch. Nineteen neurons had a significant response to at least one optimal stimulus, and 17 had a significantly greater response to one stimulus than to the other three, including 7 PC-related, 7 RA-like, 3 SA1-like, and 2 SA2-like neurons. One of each of the SA1- and SA2-like thalamic neurons responded to vibration with firing rates that were lower than those to edge or stretch but not significantly. Except in the case of PC-related neurons, the receptive field (RF) sizes were larger for these thalamic neurons than for the corresponding mechanoreceptor. Von Frey thresholds were higher than those for the corresponding human RA and SA1 mechanoreceptors. These results suggest that there is a convergence of pathways transmitting input from multiple mechanoreceptors of one type on single thalamic neurons via the dorsal columns. They are also consistent with the presence of primate thalamic elements of modality and somatotopic isorepresentation.

ATP suppresses activity in slowly adapting but not rapidly adapting mechanoreceptors in toad skin.

To test the possible role of ATP in transducing or modulating touch sensation, an isolated skin-nerve preparation from the toad, Bufo marinus, perfused on the inner side, was used to examine the effects of ATP on slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors, identified by ramp and hold indentation of the skin. ATP (1-50 mM) did not generate impulse activity in either SA or RA mechanoreceptors nor increase their responses to mechanical stimulation. Instead, ATP (> or =5 mM) reversibly and selectively suppressed impulse discharge from SA mechanoreceptors. Our results indicate that while ATP may modulate the responses of specific touch receptors, it is not involved in transducing touch into nerve impulses.

Abnormalities of mechanoreceptors in a rat model of neuropathic pain: possible involvement in mediating mechanical allodynia.

1. Peripheral nerve injury sometimes leads to the development of neuropathic pain. One of the symptoms of such neuropathic pain is mechanical allodynia, pain in response to normally innocuous mechanical stimuli. We hypothesized that sympathetically driven dysfunction of cutaneous mechanoreceptors is responsible for signaling mechanical allodynia. The present study was undertaken to identify the types of sensory receptors that potentially mediate mechanical allodynia, with the use of a rat neuropathic pain model we have developed. 2. One week to 10 days after tight ligations of the L5 and L6 spinal nerves on one side, the rats fully developed behavioral signs of mechanical allodynia on the affected hindlimb. Various cutaneous mechanoreceptors originating from the neuropathic foot were examined by single-fiber recordings from the L4 dorsal root. 3. Although no particular abnormalities were found in other types of cutaneous mechanoreceptors, an unusual type of mechanoreceptor was found to be innervating the neuropathic foot. The response characteristics of this type of receptor resemble those of rapidly adapting mechanoreceptors (RAs), but with low and irregular static discharges during a maintained mechanical stimulus. We termed this unusual type as a "modified rapidly adapting" mechanoreceptor (MRA). 4. The response characteristics of MRAs change to those of typical RAs after a systemic injection of phentolamine, an alpha-adrenergic receptor blocker. 5. We conclude that many RAs become abnormal under the influence of sympathetic efferents in neuropathic pain, so that their response patterns change to those of MRAs. We propose that this abnormality is responsible for signaling the mechanical allodynia that can be seen in neuropathic pain states such as causalgia.

Simulation of motion on the skin. III. Mechanisms used by rapidly adapting cutaneous mechanoreceptors in the primate hand for spatiotemporal resolution and two-point discrimination

1. The contribution of rapidly adapting (RA) mechanoreceptors to two-point discrimination has been evaluated by examining their ability to resolve the spacing of grating patterns shifted across the skin. The experiments test two different neural coding mechanisms that have been proposed to underlie resolution of spatial detail on the hand: 1) a rate-intensity code in which the spacing of surface features is encoded by the average frequency of firing of individual sensory afferents, and 2) an isomorphic representation of shape in which variations in the firing patterns of individual afferents reflect the spatiotemporal profile of skin indentation. 2. To measure the spatial acuity of RA mechanoreceptors innervating the hands of macaque monkeys, we displayed pairs of horizontal bars spaced 1-13 mm apart on a computer-controlled OPTACON stimulator placed over glabrous skin. Two-point resolution was measured by simultaneously pulsing pairs of rows at rates of 100, 50 and 25 Hz; each pair was shifted in tandem across the hand to simulate lateral motion. Single-fiber recordings were made from physiologically identified RA afferents in anesthetized monkeys. 3. Receptive field diameter appears to be the critical determinant of spatial resolution of gaps between two bars. RAs fire continuously if bar spacing is less than the field diameter but do not summate inputs when both active rows are contained within the field. Response profiles evoked by two bars spaced less than 4.8 mm apart can be predicted from the single-bar profiles, assuming occlusion between overlapping inputs with the strongest member dominating axonal output. Two-thirds of the RAs tested discharge 1 spike/pulse as bar patterns cross the field, yielding a uniform spike train whose frequency reflects stimulus pulse rates but fails to indicate gaps between bars. An additional 17% fire 2 spikes/pulse when the bars contact or straddle the field center, but also fail to differentiate individual stripes spaced less than 3.6 mm apart. 4. Only 17% of RAs represent gaps narrower than the field diameter. These fibers show double-peaked response profiles to bar patterns spaced at least 2.4 mm apart, firing 2 spikes/pulse as first one, and then the second stripe crosses the field center. Timing between peaks corresponds to bar spacing. Responses are reduced in amplitude when adjacent bars straddle the field center, as occlusion between simultaneous inputs prevents summation of inputs from the two stimuli. Fifteen of 16 RAs failed to resolve bars spaced 1.2 mm apart, as double-spike responses were evoked only by the leading stripe.(ABSTRACT TRUNCATED AT 400 WORDS)

Intrapulmonary receptors in the garter snake (thamnophis sirtalis)

Receptors in the respiratory system of anesthetized, unidirectionally ventilated garter snakes were analyzed from single-unit vagal recordings. Three types of receptors were found; rapidly adapting mechanoreceptors (RARs), slowly adapting pulmonary stretch receptors (SARs) and intrapulmonary chemoreceptors (IPCs). RARs gave a burst of activity when the lung was inflated or deflated. Discharge frequency of SARs increased during a sustained elevation of intrapulmonary pressure (P ip); a step increase in P ip usually caused an overshoot in receptor activity that slowly adapted to a new tonic level during the sustained inflation. The activity of intrapulmonary chemoreceptors (IPCs) decreased when airway CO 2 was raised. A sudden removal of CO 2 caused a striking overshoot in activity which slowly adapted. Receptor discharge of SARs and IPCs was studied at 20, 25 and 30°C. Discharge frequency increased with increasing temperature. The Q 10 of discharge frequency averaged 3.0 for IPCs and 1.5 for SARs. Temperature clearly had a profound effect on pulmonary receptor activity; however, the relative change of activity of IPCs or SARs to a given stimulus was similar regardless of body temperature, and since the body temperature of snakes varies considerably, this may have important implicatios regarding the control of breathing in these animals.

Mechanoreceptors in rat glabrous skin: redevelopment of function after nerve crush.

In the glabrous skin of the rat's hindfoot the same triple set of low-threshold mechanoreceptors is present as has been found in other mammals: slowly adapting (SA), rapidly adapting (RA), and very rapidly adapting Pacinian corpuscle-like (PC) receptors. Their functional characteristics were examined in normal rats and compared with those of sensitive mechanoreceptors found in the glabrous skin of the foot 2-24 wk after crush of the plantar nerves, resulting in regeneration of the transected nerve fibers. After 2 wk of nerve regeneration, low-threshold RA and SA cutaneous mechanoreceptors reappeared in the foot skin. Responses of PC receptors were recorded again after 3 wk, at which time the proportion of fibers that could be identified as low-threshold cutaneous mechanoreceptors had regained control level. Discharge patterns of regenerated cutaneous mechanosensitive receptors were very similar to those of normal skin mechanoreceptors. Their sensitivity to controlled mechanical stimulation was, however, still reduced 4 wk after the lesion. After 8 wk RA and SA receptors had regained their normal dynamic sensitivity, i.e., the responsiveness to the velocity of skin indentation. The static sensitivity of SA receptors, i.e., responsiveness to maintained skin indentation, was not consistently reestablished within 24 wk. No shift in sensitivity could be deduced from tuning curves of PC receptors examined 3-24 wk after nerve crush. In addition to the low-threshold mechanoreceptors, high-threshold (HT) mechanoreceptive fibers were found in controls and in animals with regenerating nerves. This type of fiber was most frequently found 1 wk after the nerve crush, when reinnervation of the foot started. They probably represent fibers not connected to specific mechanoreceptor end organs. Thus, functional restitution of the highly specific cutaneous mechanoreceptors occurs fairly soon after invasion of the original territory by the regenerating nerve. It is assumed that the underlying mechanism is the rapid reconnection of fibers with the end organs that have either survived during the period of denervation or regenerated subsequent to reinnervation of the skin.

Rapidly and slowly adapting mechanoreceptors in the glans penis of the cat

Sixty-one single mechanoreceptive fibers were surgically isolated from the dorsal nerve of the penis in anesthetized, mature, and sexually intact male cats. Impulse activity was recorded extracellularly. Receptive fields on the glans penis were stimulated with an accurate computer controlled mechanostimulator. Thirty-four units were categorized as rapidly adapting (RA) based on the absence of a response to sustained skin displacement. The remaining were slowly adapting (SA) units responding to sustained displacement. Most of the SA units were located in the distal smooth glans whereas RA units predominated in the proximal spiny glans. Displacement thresholds were significantly lower for RA units. All units encoded indentation velocity although the SA units were better suited to discriminate slowly moving stimuli. In addition, SA units encoded sustained displacement amplitude. Male cats with a denervated glans penis display disoriented mounting behavior disabling intromission. The presence of distally located SA mechanoreceptors suggests they may be the primary penile proprioceptors, mediating, along with the RA mechanoreceptors, successful completion of intromission.

Superposition of impulse activity in a rapidly-adapting afferent unit model.

Mechanosensory afferent units consist of a parent axon, the peripheral axonal arborization, and the branch terminal mechanoreceptors. The present work uses a mathematical model to describe the contribution of a given number of rapidly-adapting mechanoreceptors to the impulse pattern of their parent axon. In the model, impulses initiated by any driven mechanoreceptor instantaneously propagate orthodromically and antidromically. The model also incorporates the axonal absolute refractory period as well as ortho- and antidromically elicited recovery cycles. In separate computations, periodic or random (Poisson process) trains of short-duration stimuli at constant amplitude are delivered to a given number (N = 2-30) of co-innervated mechanoreceptors. The superposition of component impulse trains always departs from the theoretical ideal (Poisson process). Such departures are attributable to: (i) the number of driven mechanoreceptors, when N is small, (ii) axonal absolute refractory period, during maximal amplitude stimulation, and (iii) antidromic recovery cycles as well as absolute refractoriness, during submaximal-amplitude stimulation. Computations reveal that this "instantaneous reset" model results in the elimination of information extracted by driven mechanoreceptors. Model predictions with Poisson stimulation at varied amplitudes are compared to G-hair afferent unit responses to analogous stimulation. Qualitatively opposite results with respect to parent axonal impulse patterns imply that the axonal arborization is not simply a substrate for impulse propagation from branch terminals to parent axon.

Location and discharge properties of respiratory vagal afferents in the newborn dog

Activity from afferents of respiratory origin was recorded from filaments of the vagus nerve in puppies 1–17 days old. Animals were anesthetized with a mixture of chloralose-urethane and artificially ventilated with the chest open. A total of 256 receptors were studied of which 96% were identified as slowly adapting mechanoreceptors (SARs) and 4% as rapidly adapting mechanoreceptors (RARs). Hence the newborn has fewer spontaneously active RARs than the adult. Thirty-five percent of SARs were located in the trachea and the remainder in the bronchi: a distribution similar to that found in the adult. The transpulmonary pressure (P tp) threshold required for SAR activation was higher in the newborn than the adult for both tracheal (2.42 cm H 2O vs 0.51 cm H 2O) and bronchial (4.66 cm H 2O vs 3.66 cm H 2O) receptors. This resulted in less SAR activity at FRC in the puppy (16% of the total number of SARs in 1–17-day-old animals) compared to the adult (63%). In addition, the discharge frequency of tracheal and bronchial SARs, at any given P tp, was lower in the newborn than in the adult dog. These data suggest that the newborn has considerably less volume-related feedback during the respiratory cycle compared to the adult.

On- versus off-responses of raccoon glabrous skin rapidly adapting cutaneous mechanoreceptors.

1. The on- and off-responses of 50 raccoon median nerve fibers associated with rapidly adapting cutaneous mechanoreceptors in glabrous skin were examined under experimental conditions designed to allow comparable opportunities for on- and off-responses to occur. Trapezoidal stimuli were utilized, providing for equal stimulus indentation and retraction velocities and equal static displacement times and intertrial intervals. Principal findings were as follows: 2. At stimulus levels well above displacement and velocity thresholds for on-responses, 80% of units yielded a more vigorous on-response than off-response (as measured by the total number of ramp impulses); in 6%, the reverse was true; while in the remaining 14%, the off-discharge was absent. 3. On and off displacement thresholds were approximately equal (on median, 43 micron; off median, 42 micron). However, on velocity thresholds were significantly lower than off velocity thresholds (on median, 1.0 micron/ms; off median, 3.8 micron/ms). 4. Exponents (b) of power functions relating discharge rate to ramp velocity (frequency = a x velocityb) were consistently greater for on-responses than for off-responses, but intercept constants (a) were consistently greater for off-responses than for on-responses. 5. Previous findings that mammalian rapidly adapting (RA) mechanoreceptors possess a "linear directionality" generally favoring on-responses were confirmed. 6. Results are discussed in relation to the role of viscoelastic properties of RA mechanoreceptors and neighboring skin. It is suggested that, when considerations is also given to the mechanical properties of surrounding tissues, the Loewenstein and Skalak (18) analysis of the mode of operation of Pacinian corpuscles might also apply, at least qualitatively, to the simple dermal (rapidly adapting) corpuscle of raccoon glabrous skin.