Somatosensory research最新文献

As part of a program to explore patterns of innervation by nociceptor-related thin sensory axons in a variety of peripheral regions, we have labeled calcitonin gene-related peptide immunoreactive (CGRP-IR) nerve fibers in whole mounts of rat testicular tunica vasculosa and cornea. Efforts were undertaken to visualize the numerically significant fluoride-resistant acid phosphatase (FRAP)-containing axon population, whose peripheral endings have heretofore remained undemonstrable due to technical limitations of currently available acid phosphatase methods. Various histochemical markers that colocalize with FRAP in dorsal root ganglion (DRG) and spinal cord were examined, and a plant lectin, Griffonia simplicifolia I-B4, has been identified that not only selectively labels FRAP(+) sensory ganglion cells and central terminals in spinal cord, but also differentially stains a large number of thin axons in testicular and corneal whole mounts. Slender lectin-labeled fibers are abundant in cornea, and are distributed throughout tunica vasculosa preparations unrelated to blood vessels. CGRP-IR axons, in contrast, maintain close adherence to vascular patterns and are more coarse and varicose in appearance. Lectin staining therefore provides the first practical and specific method for visualization of peripheral FRAP(+) axons consisting principally of sensory C fibers but possibly including a small number of unmyelinated autonomic axons. It should now be feasible, using individual whole-mount preparations from various peripheral nociceptor-innervated tissues, to examine the distributions of both peptidergic and FRAP(+) fibers, which together comprise the vast majority of thin sensory axons. It may then be possible to correlate the observed anatomical patterns with knowledge regarding properties of corresponding physiologically characterized receptive fields.

Single thalamocortical neurons with receptive fields on the toes were antidromically activated by the passage of 300-microseconds, 0.5- to 10-microA pulses through glass micropipette electrodes placed within somatotopically identified regions of the digit representation of the cat first somatosensory (SI) cortex. The somatotopy of the cortex was determined using recordings from single cortical neurons (see "Methods"), and the positions of the all tracks were marked on an enlarged photograph of the postcruciate cortex. In two of the three protocols, a very precise map of the boundary between two adjacent toes was produced prior to attempting intracortical microstimulation. Slopes of the threshold-distance curves at the sites of the lowest recorded thresholds were on the order of 0.8 microA/10 micron. This value, together with information on the anatomy of the cortical arborizations of thalamocortical neurons (Landry and Deschenes, 1981), suggested that currents of 2 and 5 microA would not activate the cortical processes of thalamocortical neurons at distances greater than 50 and 90 microns, respectively. With currents below 5 microA, thalamocortical neurons could be antidromically activated at a number of sites at depths between 340 and 930 microns (layer IV and upper layer III) and between 1,050 and 1,460 microns (layer VI). A total of 13 thalamocortical neurons could be antidromically activated using current pulses of between 0.8 and 5.0 microA, from within tracks at tangential distances of 250-830 microns from the nearest track through the somatotopically appropriate region. Within somatotopically inappropriate regions, cortical neurons frequently had receptive fields on a toe adjacent to that bearing the receptive field of the thalamic neuron(s) under study. The possible relationship of somatotopically inappropriate projections to the reorganization of cortical somatotopy following digit amputation, paw amputation, and nerve section is discussed.

The distribution of fiber size in the posterior articular nerve (PAN) and medial articular nerve (MAN) of the cat's knee joint was studied by light and electron microscopy. The myelinated fibers of the PAN ranged from approximately 1 to 18 micron, with maxima at 3-4 micron and 8-9 micron. According to the classification of Boyd and Davey (1968), the PAN contained about 34% Group III fibers, 56% Group II fibers, and 10% Group I fibers. In contrast, the MAN showed a unimodal, skewed distribution, with a range from approximately 1 to 14 micron and a maximum at 3-4 micron. According to the Boyd and Davey classification, the PAN contained about 69% Group III fibers, 30% Group II fibers, and 1% Group I fibers. Unmyelinated fibers examined in the MAN showed a unimodal distribution, with a range of from 0.1 to 1.5 micron and a maximum at 0.4-0.5 micron. To differentiate between afferent and sympathetic fibers, a sympathectomy or ganglionectomy was performed on one side. The fiber size distribution indicated a considerable overlap in the diameter of the afferent and sympathetic unmyelinated fibers. Most sympathetic fibers had a diameter of between 0.8 and 0.9 micron, whereas afferent fibers showed a maximum at 0.3-0.4 micron. When data were combined for myelinated and unmyelinated fibers in the PAN, about 74% of the afferent fibers were found to belong to Groups III and IV; they are thought to terminate in noncorpuscular endings. The other 26% were found to belong to Groups I and II; they terminate in corpuscular receptors and muscle spindle primary and secondary endings.(ABSTRACT TRUNCATED AT 250 WORDS)

Two experiments were performed to study the ability of blindfolded subjects to estimate distance on the basis of proprioceptive cues. In the first experiment, subjects judged the length of metal rods that they were allowed to explore freely. With this access to positional as well as other cues, subjects' estimates were a nearly linear function of actual length. These data closely paralleled control measurements obtained under conditions of visual, rather than haptic, inspection. In the second experiment, each subject slid his or her index finger laterally along a straight path delimited by the apparatus, and then gave a magnitude estimate of the distance through which the finger had moved. Velocity of movement was manipulated by asking subjects, on each trial, to move at one of five speeds ranging from "very slow" to "very fast"; these instructions elicited velocities spanning a 100-to-1 range. Magnitude estimates of distance in this second experiment increased as a function of actual distance, but decreased as a function of velocity. This latter phenomenon resembles the dependence of perceived distance on velocity that has been shown by other investigators to occur when a stimulus object is drawn across the skin. The data of the present study are consistent with the hypothesis that the perceived length of an active movement depends on a combination of movement and position signals from primary and secondary sensory fibers in muscle spindles.

The sparse distribution of thin, principally unmyelinated sensory axons confined largely to the planar tunica vasculosa of the testis provides a suitable model for examining the fine structure of electrophysiologically characterized nerve fiber terminals. The marked sites of polymodal receptors of canine testis using the in vitro preparation devised by Kumazawa et al. (1987) were examined in serial sections traced to the terminal with the electron microscope, revealing the first micrographs of a characterized polymodal receptor ending. The inferred role of these terminals in nociception, their organelle content, and the problems encountered in interpreting our initial findings are considered in the context of the variety of morphological patterns and functional roles of thin sensory axons.

Although there is considerable evidence that the analgesic action of electrical brain stimulation is mediated in part by serotonergic (5-HT) axons in the dorsolateral funiculus (DLF) of the spinal cord, studies in the rat have questioned the existence of this pathway. In this study, we used antisera directed against a conjugate of 5-HT and bovine serum albumin (BSA) to identify immunoreactive 5-HT axons in the DLF of the rat and cat. Both light and electron-microscopic studies were performed so that the fiber caliber of the labeled axons could also be determined. We found a rich complement of immunoreactive 5-HT axons in the DLF of both rat and cat. Although these could be seen without difficulty in the normal cat, in the rat it was necessary to make a lesion of the DLF to build up the staining rostrally. Ultrastructural analysis established that almost all of the labeled axons (in rat and cat) were unmyelinated. We conclude that there are indeed 5-HT immunoreactive axons in the DLF of the rat and cat. These presumably derive from neurons of the medullary nucleus raphe magnus (NRM), which have been implicated in the descending controls exerted by opiates and electrical brain stimulation. The results suggest that previous physiological studies of the properties of the opiate-responsive, spinally projecting NRM neurons were not made from those that are 5-HT containing.

A recent model for control of spinal and medullary nociceptive neurons (Basbaum and Fields, 1984) incorporates a gamma-aminobutyric acid-ergic (GABA-ergic) cell into this circuitry and indicates that such elements could act as one substrate for presynaptic inhibition of primary afferents. This concept is supported by a variety of pharmacological and electrophysiological studies. We therefore examined the distribution of GABA-ergic activity in trigeminal subnucleus interpolaris (Vi) by focusing on the types of cells, together with dendritic and synaptic profiles, that are immunocytochemically labeled with an antiserum against glutamic acid decarboxylase (GAD). GAD occurred throughout Vi but was most concentrated in the ventrolateral quadrant and interstitial nucleus. It was localized to groups of small neurons with two to three primary dendrites, and within numerous punctate profiles suggestive of synaptic elements. Electron microscopy revealed labeled dendrites, some of which were postsynaptic to scalloped terminals of presumptive primary afferents. Other labeled dendritic elements, which were quite variable in size, engaged both GAD-labeled and unlabeled synapses. Most GAD synapses displayed clear round vesicles and formed contacts with unlabeled perikarya and a variety of dendritic processes. Numerous GAD-positive synapses were also incorporated into axoaxonic clusters, in which the GAD element was presynaptic to scalloped terminals. Others engaged in serial arrays with other unlabeled terminals, which, in turn, were presynaptic to dendrites. Occasionally, GAD synapses formed contacts with GAD-positive dendrites. These data show that GABA is localized to a variety of neuronal elements in ventrolateral Vi and the interstitial nucleus. These occur in spatial arrangements providing an anatomical substrate for postsynaptic modulation of activity in this area. GABA terminals also appear to be involved in a presynaptic inhibitory mechanism, which may, in some instances, affect transmission in primary afferents.

Fluoride-resistant acid phosphatase (FRAP) activity as characterized in rat and mouse was studied in sensory ganglion and spinal cord of several mammals, using both the Gomori lead-ion capture and azo-dye coupling methods. FRAP was specifically localized to small- and medium-diameter primary afferent neurons and inner substantia gelatinosa of all nonrodent animals studied, including rabbit, cat, dog, monkey, cow, and human. In rabbit, sciatic nerve transection resulted in depletion of enzymatic activity in ipsilateral spinal cord dorsal horn in a pattern corresponding to the distribution of central terminals of the nerve. Further analysis of the substrate specificity and pH dependence of FRAP was carried out primarily in rat sensory ganglion and spinal cord; the enzyme was found to hydrolyze a wide variety of phosphomonoesters in a relatively nonselective manner at both pH 5 and pH 7, including 5'-nucleotides, phosphorylated amino acids, and several exogenous compounds. The visualization of FRAP-like activity in several nonrodent species is discussed with reference to previous work indicating its presence only in mouse and rat. Technical factors are considered that limit the applicability of the lead-ion histochemical method in demonstration of FRAP and in efforts at functional characterization of the enzyme, especially in light of its ability to hydrolyze a broad spectrum of substrates over a wide pH range. Alternative interpretations of the expression of acid phosphatase activity in a select class of small sensory ganglion cells are suggested, including several possible non-synaptic roles of FRAP in the peripheral nervous system.

(1) The purpose of this experiment was to characterize the responses of neurons in somatosensory cortex while the hand was actively moved (stroked) across a textured surface. Surfaces consisted of horizontal gratings that varied by spatial period or ridge-groove ratio (roughness). Surfaces were attached to rectangular blocks. TOP and BOTTOM halves of each block could contain surfaces of different roughness. (2) Velocity and force of the stroke were behaviorally constrained within certain limits and continuously measured and recorded during the stroke. (3) Response samples for each neuron were obtained for repeated presentations of each surface. Statistical analyses consisted of analysis of variance and t tests across surfaces on the data of each neuron, and summary statistics on groups of neurons with similar response characteristics. The interaction effects of behavioral variables (velocity and force) were examined and found not to be significant. (4) The sample mainly consisted of rapidly adapting neurons in area 3b of somatosensory area I (SI). Three main response types were found: (a) GRADED cells showed a monotonic increase in firing rate to increasingly rougher surfaces. This effect was seen in one-third of cells studied and is consistent with other reports. These cells seem to code roughness in the magnitude of their response. (b) In some cells, response to a BOTTOM surface depended on the roughness of the preceding TOP surface. This is analogous to contrast in the visual system. These CONTRAST cells are a novel finding in the somatosensory system. (c) Some cells only responded to surfaces that were completely smooth. These "OFF"-response-type cells were seen in proximity to other cells that responded in a reciprocal fashion to surfaces with ridges, but not to smooth surfaces. SMOOTH cells did not respond to punctate or passively applied stimuli, and therefore could not be classified by adaptation of the responses. (5) An increase in firing rate as spatial period (roughness) increases (with a constant ratio of ridge to groove) seems contrary to vibratory models of texture perception. As spatial period increases, temporal frequency decreases, and thus "tuned" cells should show a decreased response rate. Yet GRADED cells showed an increased response. In addition, response varied on surfaces with different groove size, where spatial period, and thus temporal period, was constant. This suggests that in rapidly adapting neurons, at least for these simple surfaces, texture is coded by the magnitude of the firing rates rather than by its temporal fidelity.(ABSTRACT TRUNCATED AT 400 WORDS)

The fluorescent dye retrograde tracing technique, using fast blue in combination with fluorogold, was used to examine thalamocortical projections from the ventrobasal complex to primary somatosensory cortex in chronic spinal cats that sustained T12 cord transection at 2 weeks of age. Following cord transection at this age, it has been shown that forelimb afferents can excite the deprived hindlimb projection zone, in addition to the region of somatosensory cortex that they normally occupy (McKinley et al., 1987). These two regions of cortex are separated by over 10 mm, thus facilitating the determination of whether the forelimb representation in "hindlimb cortex" is derived from the sector of the ventrobasal complex of the thalamus representing the forelimb, hindlimb, or both. Injections of the two dyes into separate regions of the cortex that were excited by the same peripheral forelimb receptive fields produced single labeling of two nonoverlapping clusters of thalamic neurons. This finding suggests that the projections for these two areas are independent and distinct, and indicates that altered thalamocortical projections do not contribute the critical component underlying reorganizational changes observed at the cortical level after spinal cord transection. It is hypothesized that the degree of reorganization required to achieve the magnitude of change observed in the cortex must occur below the level of the thalamocortical relay.