Slowly Adapting Type 1 Research Articles

Overexpression of neurotrophin‐3 enhances the mechanical response properties of slowly adapting type 1 afferents and myelinated nociceptors

Constitutive overexpression of neurotrophin-3 (NT3) in murine skin results in an increased number of sensory neurons within the dorsal root ganglia, an increase of myelinated axons in cutaneous nerves, hyperinnervation of the skin, and an increased number of Merkel cells found in flank skin. Here we used a saphenous skin/nerve preparation to determine if these anatomical changes affect the functional response characteristics of cutaneous sensory neurons. Overexpression of NT3 significantly increased the responses of slowly adapting type 1 (SA1) low-threshold mechanoreceptors and Adelta high-threshold mechanoreceptors to suprathreshold mechanical stimulation. It also resulted in significantly faster conduction velocities of SA1 fibers. In contrast to earlier findings in flank skin, no differences were noted in the numbers of Merkel cells in the touch domes in hindlimb skin of NT3-overexpressing mice. In addition, the number of dermal Merkel cells, located around hair follicles on the dorsum of the foot, was reduced by 55%. The increase in mechanical sensitivity was found to correlate with significant increases in the expression of acid-sensing ion channels (ASIC) 1 and 3. Additional experiments using intracellular recordings and staining procedures confirmed that at least some cutaneous myelinated nociceptors and SA1 mechanoreceptors stained positively for both trkC and ASIC3. These results indicate that cutaneous NT3 overexpression alters the response properties of specific cutaneous sensory neurons, and that these changes may be due to the modulation of putative mechanosensitive ion channels.

A Continuum Mechanical Model of Mechanoreceptive Afferent Responses to Indented Spatial Patterns

Information about the spatial structure of tactile stimuli is conveyed by slowly adapting type 1 (SA1) and rapidly adapting (RA) afferents innervating the skin. Here, we investigate how the spatial properties of the stimulus shape the afferent response. To that end, we present an analytical framework to characterize SA1 and RA responses to a wide variety of spatial patterns indented into the skin. This framework comprises a model of the tissue deformation produced by any three-dimensional indented spatial pattern, along with an expression that converts the deformation at the receptor site into a neural response. We evaluated 15 candidate variables for the relevant receptor deformation and found that physical quantities closely related to local membrane stretch were most predictive of the observed afferent responses. The main outcome of this study is an accurate working model of SA1 and RA afferent responses to indented spatial patterns.

Spatiotemporal Receptive Fields of Peripheral Afferents and Cortical Area 3b and 1 Neurons in the Primate Somatosensory System

Neurons in area 3b have been previously characterized using linear spatial receptive fields with spatially separated excitatory and inhibitory regions. Here, we expand on this work by examining the relationship between excitation and inhibition along both spatial and temporal dimensions and comparing these properties across anatomical areas. To that end, we characterized the spatiotemporal receptive fields (STRFs) of 32 slowly adapting type 1 (SA1) and 21 rapidly adapting peripheral afferents and of 138 neurons in cortical areas 3b and 1 using identical random probe stimuli. STRFs of peripheral afferents consist of a rapidly appearing excitatory region followed by an in-field (replacing) inhibitory region. STRFs of SA1 afferents also exhibit flanking (surround) inhibition that can be attributed to skin mechanics. Cortical STRFs had longer time courses and greater inhibition compared with peripheral afferent STRFs, with less replacing inhibition in area 1 neurons compared with area 3b neurons. The greater inhibition observed in cortical STRFs point to the existence of underlying intracortical mechanisms. In addition, the shapes of excitatory and inhibitory lobes of both peripheral and cortical STRFs remained mostly stable over time, suggesting that their feature selectivity remains constant throughout the time course of the neural response. Finally, the gradual increase in the proportion of surround inhibition from the periphery to area 3b to area 1, and the concomitant decrease in response linearity of these neurons indicate the emergence of increasingly feature-specific response properties along the somatosensory pathway.

Vibratory Adaptation of Cutaneous Mechanoreceptive Afferents

The objective of this study was to investigate the effects of extended suprathreshold vibratory stimulation on the sensitivity of slowly adapting type 1 (SA1), rapidly adapting (RA), and Pacinian (PC) afferents. To that end, an algorithm was developed to track afferent absolute (I0) and entrainment (I1) thresholds as they change over time. We recorded afferent responses to periliminal vibratory test stimuli, which were interleaved with intense vibratory conditioning stimuli during the adaptation period of each experimental run. From these measurements, the algorithm allowed us to infer changes in the afferents' sensitivity. We investigated the stimulus parameters that affect adaptation by assessing the degree to which adaptation depends on the amplitude and frequency of the adapting stimulus. For all three afferent types, I0 and I1 increased with increasing adaptation frequency and amplitude. The degree of adaptation seems to be independent of the firing rate evoked in the afferent by the conditioning stimulus. In the analysis, we distinguished between additive adaptation (in which I0 and I1 shift equally) and multiplicative effects (in which the ratio I1/I0 remains constant). RA threshold shifts are almost perfectly additive. SA1 threshold shifts are close to additive and far from multiplicative (I1 threshold shifts are twice the I0 shifts). PC shifts are more difficult to classify. We used an integrate-and-fire model to study the possible neural mechanisms. A change in transducer gain predicts a multiplicative change in I0 and I1 and is thus ruled out as a mechanism underlying SA1 and RA adaptation. A change in the resting action potential threshold predicts equal, additive change in I0 and I1 and thus accounts well for RA adaptation. A change in the degree of refractoriness during the relative refractory period predicts an additional change in I1 such as that observed for SA1 fibers. We infer that adaptation is caused by an increase in spiking thresholds produced by ion flow through transducer channels in the receptor membrane. In a companion paper, we describe the time-course of vibratory adaptation and recovery for SA1, RA, and PC fibers.

Representation of orientation in the somatosensory system

In this paper we discuss how orientation is represented and transformed in the somatosensory system. Information about stimulus orientation plays an important role in sensory processing. In touch it provides critical information about how stimuli are positioned on the hand, which is important for grasping and lifting objects. It also provides important information about tactile shape. Psychophysical studies show that humans have a high capacity to discriminate the orientation of shapes and gratings indented into the finger pad. Further, these studies demonstrate that orientation discrimination is a reliable and stable method for assessing tactile spatial acuity. Neurophysiological studies suggest that orientation information is processed by the slowly adapting type 1 (SA1) afferent system. While orientation is poorly represented in the responses of individual afferent fibers, it is well represented in the population response properties of peripheral SA1 afferents and in the responses of central neurons in the primary (S1) and secondary (S2) somatosensory cortex. In S2, neurons with orientation selective and orientation non-selective responses tend to have large receptive fields that span multiple pads on multiple digits. Neurons in S2 that are orientation selective have similar tuning functions on different finger pads. These neurons may provide position-invariant responses or may be responsible for integrating features across hands, which is important for haptic object recognition of large shapes from the hand. Neurophysiological studies in trained animals show that the responses of about 85% of the neurons in S2 are affected by the animals focus of attention and that attention to the orientation of a bar modifies both the mean firing rate (i.e. gain) of neurons encoding orientation information and the degree of synchronous firing between pairs of neurons.

Neural Coding Mechanisms Underlying Perceived Roughness of Finely Textured Surfaces

Combined psychophysical and neurophysiological studies have shown that the perceived roughness of surfaces with element spacings of >1 mm is based on spatial variation in the firing rates of slowly adapting type 1 (SA1) afferents (mean absolute difference in firing rates between SA1 afferents with receptive fields separated by approximately 2 mm). The question addressed here is whether this mechanism accounts for the perceived roughness of surfaces with element spacings of <1 mm. Twenty triangular and trapezoidal gratings plus a smooth surface were used as stimulus patterns [spatial periods, 0.1-2.0 mm; groove widths (GWs), 0.1-2.0 mm; and ridge widths (RWs), 0-1.0 mm]. In the human psychophysical studies, we found that the following equation described the mean roughness magnitude estimates of the subjects accurately (0.99 correlation): 0.2 + 1.6GW - 0.5RW - 0.25GW(2). In the neurophysiological studies, these surfaces were scanned across the receptive fields of SA1, rapidly adapting, and Pacinian (PC) afferents, innervating the glabrous skin of anesthetized macaque monkeys. SA1 spatial variation was highly correlated (0.97) with human roughness judgments. There was no consistent relationship between PC responses and roughness judgments; PC afferents responded strongly and almost equally to all of the patterns. Spatial variation in SA1 firing rates is the only neural code that accounts for the perceived roughness of surfaces with finely and coarsely spaced elements. When surface elements are widely spaced, the spatial variation in firing rates is determined primarily by the surface pattern; when the elements are finely spaced, the variation in firing rates between SA1 afferents is determined by stochastic variation in spike rates.

Tactile directional sensibility: peripheral neural mechanisms in man

Tactile directional sensibility, i.e. the ability to tell the direction of an object’s motion across the skin, is an easily observed sensory function that is highly sensitive to disturbances of the somatosensory system. Based on previous psychophysical experiments on healthy subjects it was concluded that directional sensibility depends on two kinds of information from cutaneous mechanoreceptors; spatio-temporal information and information about friction-induced changes in skin stretch. In the present study responses to similar probe movements as in the psychophysical experiments were recorded from human single mechanoreceptors in the forearm skin. All slowly adapting type 2 (SA2) units were spontaneously active, and with increasing force of friction their discharge rates were modified by probe movements at increasing distances from the Ruffini end-organ, reflecting the high stretch-sensitivity of these units. Slowly adapting type 1 (SA1) and field units responded to the moving probe within well-defined skin areas directly overlying the individual receptor terminals, and compared to the SA2 units their response properties were less dependent on the force of friction. The results suggest that SA1 and field units have the capacity to signal spatio-temporal information, whereas a population of SA2 units have the capacity to signal direction-specific information about changes in lateral skin stretch.

SA1 and RA receptive fields, response variability, and population responses mapped with a probe array.

Twenty-four slowly adapting type 1 (SA1) and 26 rapidly adapting (RA) cutaneous mechanoreceptive afferents in the rhesus monkey were studied with an array of independently controlled, punctate probes that covered an entire fingerpad. Each afferent had a receptive field (RF) on a single fingerpad and was studied at 73 skin sites (50 mm2). The entire array was lowered to 1.6 mm below the point of initial skin contact (the background indentation) before delivering single-probe indentations. SA1 and RA responses differed in several ways. 1) SA1 RF boundaries were affected much less by indentation depth than were RA boundaries, and the SA1 RF areas were much more uniform in size. The mean SA1 RF area grew from 5.1 to 8.8 mm2 as the indentation depth increased from 50 to 500 microm; the mean RA RF area grew from 5.5 to 22.4 mm2 over the same intensity range. 2) SA1 RFs were more elongated than RA RFs. Elongated RFs were oriented in all directions relative to the skin ridges and the finger axis. 3) SA1 impulse rates were linear functions of indentation depth at all probe locations in the RF; RA responses tended toward saturation beginning at 100 microm indentation depth when the probe was over the HS. Similarities between SA1 and RA responses were that 1) both were extremely repeatable with SDs < 1 impulse per trial and 2) both had population responses (number of impulses) that were nearly linear functions of indentation depth. However, SA1s represented increasing indentation depth by increasing impulse rates in a small, relatively constant group of afferents, whereas the RAs represented increasing indentation depth predominantly by the recruitment of new afferents at a distance.

Surround suppression in the responses of primate SA1 and RA mechanoreceptive afferents mapped with a probe array.

Twenty-four slowly adapting type 1 (SA1) and 26 rapidly adapting (RA) cutaneous mechanoreceptive afferents in the rhesus monkey were studied with an array of independently controlled, punctate probes that covered an entire fingerpad. Each afferent had a receptive field (RF) on a single fingerpad and was studied at 73 skin sites (50 mm2). The entire array was lowered to 1.6 to 3.0 mm below the point of initial skin contact (the background indentation) before delivering indentations with one to seven probes. Indentations were generally limited to 100 microm to minimize gross mechanical interactions. There were two major, new findings. 1) The discharge rates of both SA1 and RA afferents were strongly affected by the number of probes indenting the RF simultaneously. The effect was exponential. Each increase in probe number reduced the response by 24% in SA1 and 12% in RA afferents on average. When seven probes indented the skin simultaneously, the impulse rates in SA1 and RA afferents were reduced to 20 and 40% of the rates evoked by a single probe at the hot spot (all indentations were 100 microm). This shows that before any synaptic interaction in the CNS there is already a mechanism analogous to surround inhibition that suppresses an afferent's responses to uniform indentation and makes it especially sensitive to deviations from spatial uniformity. 2) The responses of both SA1 and RA afferents were independent of background array depth over the range from 1.6 to 3 mm below the point of initial skin contact. This shows that the neural responses to elements raised above a background are independent of the applied force over a wide range of forces. To relate the background depths to indentation force and to compare humans and monkeys, we studied the biomechanics of indentation with a uniform surface. A remarkable result is that the force-displacement relationships in humans and monkeys were the same; the skin is highly compliant for the first 2-3 mm of indentation and then becomes much stiffer. The results were the same in alert humans and monkeys and in monkeys anesthetized with pentobarbital. Ketamine anesthesia made the skin much stiffer and reduced the compliant range substantially.

Cutaneous overexpression of NT-3 increases sensory and sympathetic neuron number and enhances touch dome and hair follicle innervation.

Target-derived influences of nerve growth factor on neuronal survival and differentiation are well documented, though effects of other neurotrophins are less clear. To examine the influence of NT-3 neurotrophin overexpression in a target tissue of sensory and sympathetic neurons, transgenic mice were isolated that overexpress NT-3 in the epidermis. Overexpression of NT-3 led to a 42% increase in the number of dorsal root ganglia sensory neurons, a 70% increase in the number of trigeminal sensory neurons, and a 32% increase in sympathetic neurons. Elevated NT-3 also caused enlargement of touch dome mechanoreceptor units, sensory end organs innervated by slowly adapting type 1 (SA1) neurons. The enlarged touch dome units of the transgenics had an increased number of associated Merkel cells, cells at which SA1s terminate. An additional alteration of skin innervation in NT-3 transgenics was an increased density of myelinated circular endings associated with the piloneural complex. The enhancement of innervation to the skin was accompanied by a doubling in the number of sensory neurons expressing trkC. In addition, measures of nerve fibers in cross-sectional profiles of cutaneous saphenous nerves of transgenics showed a 60% increase in myelinated fibers. These results indicate that in vivo overexpression of NT-3 by the epidermis enhances the number of sensory and sympathetic neurons and the development of selected sensory endings of the skin.

Noise-enhanced information transmission in rat SA1 cutaneous mechanoreceptors via aperiodic stochastic resonance.

1. Aperiodic stochastic resonance (ASR) is a phenomenon wherein the response of a nonlinear system to a weak aperiodic input signal is optimized by the presence of a particular, nonzero level of noise. Our objective was to demonstrate ASR experimentally in mammalian cutaneous mechanoreceptors. 2. Experiments were performed on rat slowly adapting type 1 (SA1) afferents. Each neuron was subjected to a perithreshold aperiodic stimulus plus noise. The variance of the noise was varied between trials. The coherence between the aperiodic input stimulus and the response of each SA1 afferent was computed. 3. Of the 12 neurons tested, 11 showed clear ASR behavior: as input noise variance was increased, the stimulus-response coherence rapidly increased to a peak and then slowly decreased. These findings were in contrast with those for the average firing rate, which increased monotonically as a function of input noise variance. 4. This work shows that noise can serve to enhance the response of a sensory neuron to a perithreshold aperiodic input signal. These results suggest a possible functional role for input noise in sensory systems. These findings also indicate that it may be possible to introduce noise artificially into sensory neurons to improve their abilities to detect arbitrary weak signals.

Chapter 2 Segmental influence of slowly-adapting cutaneous mechanoreceptors on γ motoneurones revealed by cross-correlation of unit discharges in the cat

Cross-correlations between the discharges of individual cutaneous afferents and gamma motoneurones have been constructed in the spinal, decerebrated cat. The discharges of single receptors in the sural nerve field from the heel were recorded in dorsal root ganglia. Background discharges of gamma motoneurones and the responses to heel stimulation were recorded from cut filaments of the muscle nerve to gastrocnemius medialis of the same leg. Slowly-adapting afferents were stimulated by steady application of a probe to the receptive field whereas rapidly-adapting afferents required continuous movement to sustain discharge of a receptor. Cross-correlation between the discharges of 17 out of 39 slowly-adapting, type-1 (SA1) mechanoreceptors and gamma motoneurones revealed sharp increases in probability of gamma motoneurone discharge that were delayed with respect to the afferent discharge. The peaks were of short duration with widths at half maximum in the range 2-7 ms and rise times of 1 to 4 ms. Deducting peripheral conduction times gave central delays of 3-6.5 ms for gamma motoneurone facilitation. These delays were comparable to those of gamma motoneurone excitation seen in response to electrical stimulation of the sural nerve at 1.5 to 4 times threshold. No short duration peaks were seen in correlograms between hair follicle (n = 29) or slowly-adapting type-2 (SA2) (n = 11) afferents and gamma motoneurones. It is concluded that a single impulse from a SA1 afferent from the hairy skin of the heel is able to facilitate the discharge of gamma motoneurones to the ipsilateral gastrocnemius muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Chapter 6 Responsiveness of slowly adapting cutaneous mechanoreceptors after close arterial infusion of neomycin in cats

This chapter compares the acute effects of neomycin on SA1 and SA2 receptors in cats with the aim of determining whether or not Merkel cells are the site of mechano-electric transduction in SAl receptors. Close arterial infusion of the aminoglycoside neomycin strongly suppresses the excitability of slowly adapting type 1 (SA1) cutaneous mechanoreceptors in the cat. Assuming that mechano-electric transduction takes place in the Merkel cells, there are two possible target sites for the action of neomycin, the transducer itself as well as the synaptic link between Merkel cell and nerve terminal. The greater reduction in responsiveness in SAl than in SA2 receptors is in support of the idea that in the SA1 receptors neomycin acts on two target sites: the mechanoelectric transducer in the Merkel cell and the putative synapse between the Merkel cell and the adjoining nerve terminal.

Sensory receptors and their afferents in the caudal sympathetic nerve of the domestic duck.

The behavioural reactivity of the visceral receptors and their afferents in the caudal sympathetic nerve (part of synsacral sympathetic chain) of domestic duck (Anas platyrhynchos) was studied using electrophysiological techniques to examine their involvement in different physiological functions. In total, 114 single unit activities were recorded from the caudal sympathetic nerve of duck. Receptors were classified according to location: in the anal sphincter (32 units), in the mucous membrane of the cloaca (45 units), at the branching point of the blood vessels over the rectum and adjacent mesentery (10 units), at the base of the feather follicles in and around the vent (17 units), and in the ventral and lateral lower abdominal wall muscle (10 units). Both spontaneous and non-spontaneous receptors responded to mechanical stimuli; average frequency of discharge of non-spontaneous units being much higher. Most of these receptors were of the rapidly-adapting type. Only some receptors in the abdominal muscle layer, anal sphincter and mucous membrane of hind gut were of the slowly-adapting type. Some of the latter responded to intraluminal distension pressure. Except for responses to succinylcholine chloride by receptors in the abdominal wall muscles and some units in the external anal sphincter, mechanosensitive receptors were not responsive to chemical stimuli. The discharge rate of the receptors at the base of the feather follicles varied according to the strength of stimulus. Conduction velocity of the caudal sympathetic afferent fibres ranged from 2.5 to 45 m/sec.

Afferent impulses in the gastric and oesophageal branch of the vagal nerve of toad

Abstract The function of vagal gastric and oesophageal mechano-receptors was studied by means of recording the afferent discharges from a single or from several afferent nerve fibers dissected from a gastric and oesophageal branch of the vagal nerve. Three different types of mechano-receptors were found in the gastric wall. Type A: Rapidly-adapting type, situated in the mucous membrane or in the submucosa of the oesophageal border of the cardia, and which do not respond to peristaltic contraction of the stomach wall. Type B: Slowly-adapting type, situated in the muscular layer and responsive to distension and contraction of the stomach. Type C: Slowly-adapting type, connected to the non-myelinated fiber, situated in the muscular layer, and which respond to distension and contraction of the gastric wall. In the oesophagus the same three types were found. However, the number of rapidly-adapting type receptors is far larger than the other type of receptors. It has been concluded that the oesophageal receptors mainly send information about the passing of food and the vagal gastric receptors send information concerning the degree of fullness or emptiness and motility of the stomach.

STRETCH RECEPTOR ORGANS IN SQUILLA MANTIS LATR. (CRUSTACEA: STOMATOPODA).

ABSTRACT Structures which have been described as muscle receptor organs were found to respond to experimentally applied stretch. The presence of both slowly-adapting and fast-adapting receptors was determined in those organs where two sensory cells and two receptor muscles have been described, i.e. in the abdomen and posterior four thoracic segments. In the fourth thoracic segment, with two cells on a single receptor muscle, one organ is slowly-adapting and the other fast-adapting, with properties not distinguishable from those where separate receptor muscles are present. In the third thoracic segment, with a single cell and receptor muscle, the organ is slowly-adapting. In the second thoracic segment a slowly-adapting cell was discovered. It is without a receptor muscle or accessory innervation and resembles an N-cell of the Decapoda. The reactions of the abdominal organs to acetylcholine and to y-amino butyric acid are qualitatively similar to those in Decapoda. The series of stretch-sensitive organs in Squilla and in Decapoda are compared. The evidence supports the hypothesis that there was, in the trunk of the primitive Malacostraca, a segmentally arranged series of slowly-adapting and fast-adapting receptor organs, that anatomical simplification of the anterior organs has occurred progressively with the development of the carapace and that N-cells are derived from the slowly-adapting type.