Somatosensory research最新文献

We used wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) as an anterograde tracer to label the terminals of the lemniscal, spinothalamic, and trigeminothalamic pathways in the ventrobasal complex of the rat thalamus (VB). The use of benzidine dihydrochloride (BDHC) as the chromogen allowed us to view the labeled profiles with the electron microscope and permitted us to compare the morphology of the terminals from the various pathways. We found that all the labeled somatosensory pathways terminate in the VB in the form of large terminals that contain round synaptic vesicles and make numerous asymmetrical synaptic contacts, usually with dendritic protrusions and proximal dendrites. The present results demonstrate that pathways conveying noxious and non-noxious somatosensory information terminate upon thalamic neurons with synaptic terminals having similar morphological features.

The thermal sensitivity of three humans and two rhesus monkeys was measured behaviorally, using the "yes-no" paradigm of the Theory of Signal Detection. The aim was to evaluate the monkey's thermal-sensing system as a model for that of humans. Three of the principal variables of human thermal sensations--rate of the temperature change, area of stimulation, and site of stimulation--were held constant. The other three variables--adapting skin temperature (AT), intensity, and direction of the temperature change--were varied systematically. Systematic differences between species were not evident for warming or cooling stimuli. Isodetectability curves (d'e = 1) for small cooling stimuli plotted as a function of the AT were isomorphic, and the points for the human and monkey subjects were frequently superimposed. Isodetectability curves for warming stimuli, on the other hand, had similar shapes for ATs between 33 degrees and 40 degrees C, but the points for the different subjects were not superimposed. At ATs below 30 degrees C, one of the two humans in the warming series and the two monkeys continued to show similarly shaped curves, but the other human was markedly different. Qualitative descriptions of the thermal sensations obtained during threshold measurements of human subjects, reported previously, suggest that this unusual subject probably adopted a criterion qualitatively different from that used by the other subjects. The data presented here and in combination with previously published work from this laboratory (Kenshalo, 1970) suggest that thermal stimuli produce similar sensations in rhesus monkeys and humans, and that the neural systems responsible for coding AT and temperature change in the two species are fundamentally similar.

The thermal sensitivities of three humans and one monkey were measured using the "yes-no" paradigm based on the Theory of Signal Detection. The aim was to evaluate the monkey's thermal-sensing system as a model for that of humans. Three of the principal variables of human thermal sensations--the temperature to which the skin was adapted, the rate of temperature change, and the site of application of the thermal stimuli--were held constant. The other three variables--area of stimulation, intensity, and direction of the temperature change--were varied systematically. All four subjects displayed spatial summation for both warming and cooling. Isodetectability curves (d'e = 1) to small temperature changes, both for humans and for the monkey, could reasonably be fitted by the function I = kappa A-b, where I is stimulus intensity, A is the area of stimulation, and b is the rate at which spatial summation occurred. The rate of summation, b, to warming stimuli for the humans ranged from 0.60 to 1.14, while that for the monkey was 0.14. The rate of summation to cooling stimuli for the humans ranged from 0.50 to 0.87, while that for the monkey was 0.43. The main species difference was that summation on the monkey palm all but ceased for both warming and cooling stimuli applied to areas larger than 4 cm2. Data from the human subjects did not demonstrate an upper limit of spatial summation. However, there was an indication that the human subjects would show a ceiling for spatial summation near the largest area tested in this study. Thus, when considering the spatial extent of a thermal stimulus and its influence upon thermal sensations, it may be more appropriate to compare areas relative to body size, rather than absolute values.

In order to test the possibility that the dorsal columns (DCs) contribute to temporal resolution of tactile stimuli, Macaca speciosa monkeys were trained to discriminate different frequencies of stimulation delivered to the glabrous surface of the left foot. Brief (11-msec) pulses of 550-micron indentation from the skin surface were presented for 1 sec at a standard rate of 10 pulses per second (pps), and subsequent trains of the same duration either were replications of the standard or consisted of a higher (comparison) frequency of up to 35 pps. Correct performance consisted of a lever press in response to the comparison stimulus when it occurred as the second or third train in a trial. Signal detection analysis of response tendencies in the second stimulus interval revealed difference threshold values of 2.8 pps, on the average, for 75% correct responding. Transections of the ipsilateral dorsolateral column or the contralateral anterolateral column or both did not significantly affect discrimination of the frequency of cutaneous stimulation. However, following interruption of the ipsilateral DC, two monkeys could not discriminate 10 from 35 pps throughout testing for more than 1 year. These results contrast with a preservation of spatiotactile resolution that has been demonstrated repeatedly for animals following lesions of the DCs or the lateral columns, indicating that a unique function of the DC pathway relates to temporal coding.

The present experiments are based upon evidence that neurons may selectively take up at their terminals, and retrogradely transport, the same chemical they use as a neurotransmitter or its analogues. In an attempt to identify dorsal root ganglion (DRG) neurons that use glutamic acid as a neurotransmitter, [3H]D-aspartate ([3H]D-Asp) was chosen as a marker, since it is a metabolically inert amino acid known to be taken up by the same affinity mechanism as L-aspartate and L-glutamate. Adult rats and cats received injections of 50 nl to 1.5 microliter of [3H]D-Asp (500 microCi/microliter) in the dorsal horn of cervical segments (C3 to C6). At 9 to 48 hr after injection, all animals were perfused with 5% glutaraldehyde. After sections were processed for autoradiography, the DRG neurons situated most closely to the injection site were chosen from representative cases, and the number and cross-sectional area of labeled and unlabeled perikarya with a nucleolus in the plane of the section were calculated. In rats, about 4% of the sampled DRG neurons were autoradiographically labeled, and the mean perikaryal area of these neurons was about twice that of unlabeled perikarya. In cats, the percentage of labeled perikarya ranged between 6.5% and 13.27% of the sampled population. The ratio of the mean perikaryal area of labeled neurons to that of unlabeled neurons ranged between 1.6 and 2.5. In a control cat injected with [3H]proline at C7, all perikarya in the C7 DRG were autoradiographically labeled. However, with injection of [3H]gamma-aminobutyric acid ([3H]GABA) selective retrograde labeling was observed. Quantitative data in rat showed that perikarya labeled at the C6 level after injection of this amino acid constituted about 8% of the sample population in C6 DRG. The ratio of the size of labeled to unlabeled perikarya was 2.02. In one cat injected with [3H]GABA at caudal C3, the largest number of labeled perikarya were in C4 DRG and comprised up to 5.32% of the sampled population. The ratio of the size of labeled to unlabeled perikarya was 1.57. The results in cases of injection with [3H]D-Asp may be interpreted as consistent with the idea that a fraction of DRG neurons use glutamate and/or aspartate as neurotransmitter(s).(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophysiological studies have described four major tactile areas in the rat cerebellar cortex. These areas are in crus I, crus II, the paramedian lobule (PML), and the uvula, and a major portion of each is related to the ipsilateral orofacial region. This study demonstrates that neurons in trigeminal nucleus oralis (Vo) that project to the orofacial portions of these four major tactile areas are localized in the dorsomedial (DM) subdivision of the nucleus. The distribution, light-microscopic morphology, and relative densities of trigeminocerebellar neurons within DM, retrogradely labeled with horseradish peroxidase (HRP) following injections into each of the four major tactile areas, were analyzed and compared as well as correlated with the myelo- and cytoarchitecture of DM observed in Nissl sections, 1-micron sections, and Golgi material. On the basis of myelo- and cytoarchitectonic as well as trigeminocerebellar connectional criteria, three portions of DM were identified: caudal DM (CDM), middle DM (MDM), and rostral DM (RDM). The greatest portion of DM is made up of MDM (1.3 mm long), which can be further subdivided into dorsal (MDMd) and ventral (MDMv) zones. CDM forms the caudal 800 microns of DM, while RDM makes up the rostral 280 microns of the subdivision. Longitudinally running deep axon bundles permeate CDM, MDMv, and RDM, but are conspicuously absent from MDMd. The majority of neurons found throughout CDM, MDMv, and RDM have medium-sized (15- to 30-microns) somata and can be divided into two types on the basis of their somatodendritic morphology. CDM, MDMv, and RDM also contain a small neuronal cell type (5- to 15-microns cell body) that is encountered less frequently than either one of the two types of medium-sized cells. A fourth type of neuron with a large (25- to 50-microns) fusiform- to pyramidal-shaped cell body is the least frequently observed neuronal cell type and is located principally in CDM and MDMv. MDMd contains a fifth type of neuron characterized by a small (5- to 15-microns) oval soma. Data from the retrograde HRP experiments show that all five of these neuronal cell types in their respective portions of DM project to one or more of the orofacial portions of the four major tactile areas of the cerebellar cortex. Many medium-sized neurons of both types in CDM, MDMv, and RDM project to crus I, crus II, and/or PML.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of sympathetic efferent activity on slowly adapting Type I receptors in the hairy skin of cats were studied by recording from single afferent units in the saphenous nerve. Stimulation of the sympathetic trunk at 10 Hz had predominantly excitatory effects, which were seen in some units as the development of a background discharge in the absence of overt mechanical stimulation, or in most other units as a reduction in the threshold for mechanical activation. These effects generally persisted throughout the 3-min period of sympathetic stimulation (SS). The percentage of afferent units that began to discharge during SS was significantly greater in female cats than in males (53% vs. 19%). An increase in the force exerted by the skin on the stimulus probe was also observed during SS. Several tests were conducted to assess possible neurochemical and mechanical mechanisms of action. Administration of the alpha-adrenergic blocking agent phentolamine produced a marked reduction in the sympathetic effects. However, histochemical analysis of sections from the touch domes showed no catecholamine fluorescence near the sensory fibers. Cessation of local blood flow just prior to SS, produced by occlusion of the descending aorta, had no apparent effect on the sympathetically induced changes in afferent activity. It was concluded that sympathetic activity has an excitatory action on most Type I afferents in the cat. Because this sympathetic action is neither replicated nor altered by aortic occlusion, it appears not to be mediated by changes in blood flow. It also appears not to be mediated by direct neurotransmitter action on the sensory receptor, because no catecholamine fluorescence was observed, yet the action was blocked by an alpha-adrenergic blocker. It is likely, therefore, that this sympathetic action is mediated by some unidentified mechanical response within the skin.

Sensory nerves innervating rat distal limb skin were labeled by axonal transport of an enzyme-lectin conjugate injected into lumbar dorsal root ganglia (DRG), with emphasis on tracing the course of the thin axons. Selective neonatal neurotoxin destruction of most unmyelinated sensory or sympathetic axons was achieved by treatment with capsaicin (CAP) and 6-hydroxydopamine (6-OHDA), respectively. The relationship of substance P-immunoreactive (SPI) axons to the patterns of axonal transport-labeled thin axons was compared in normal and neurotoxin-treated animals. SPI is restricted to a limited population of unmyelinated axons, and electron-microscopic observation reveals its total absence in myelinated axons. SPI fibers of sensory origin, as determined by CAP susceptibility, can be traced into the epidermal stratum spinosum, in relation to guard hair follicles, mast cells, and a specific class of small blood vessels. These morphological features are not eliminated by neurotoxin sympathectomy, and some are inferred to contribute to the initial events associated with the neurogenic vasodilation and plasma extravasation associated with the inflammatory response. A re-evaluation of the concept of "free nerve endings" is suggested in the context of the variety of afferent and efferent patterns displayed by sensory peptidergic unmyelinated axons, their putative nociceptive role, and the functional diversity of sensory C fibers.

Intracellular responses to stimulation of the dorsal column (DC) and dorsolateral funiculus (DLF) were recorded in cells of the thalamic ventrobasal complex (VB) in anesthetized cats, with the dorsal funiculi either intact or isolated. The responsiveness of VB neurons was tested using graded stimulation, paired-shock, and interaction techniques. Of the 60 VB neurons thoroughly studied, 50 responded to stimulation of the DC with excitatory postsynaptic potentials (EPSPs) followed by inhibitory postsynaptic potentials (IPSPs); half of these 50 neurons responded to stimulation of the DLF with the same pattern, whereas no IPSPs could be elicited in the remaining neurons. The majority of EPSPs could be fractionated into unitary components during graded electrical stimulation. The number of such components observed was greater after DLF than after DC stimulation. In most neurons, the DLF-evoked EPSPs were smaller in amplitude than the DC-evoked EPSPs. Paired-shock stimulation facilitated the DLF excitatory responses. The amplitude of IPSPs induced by DLF stimulation was significantly smaller than that evoked by DC stimulation, and DC stimulation reduced the excitatory response to subsequent DLF stimulation. The data support the known dominance of the DC pathway in the cat.

Experiments were performed to determine whether thalamic neurons send collaterals to more than one subdivision of postcentral somatosensory cortex, and to evaluate the fidelity of somatotopic connections between cortical representations of the body surface. After microelectrode recordings identified the locations of the representations of the fingertips along the border of area 3b with area 3a and along the border of area 1 with area 2, one tracer, tritiated N-acetyl wheatgerm agglutinin ([3H]WGA), was injected into the rostral representation at the 3a-3b border, and another, wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP), was injected into the caudal representation at the 1-2 border. The results indicate that three thalamic regions are interconnected with both border zones. Regions of overlapping retrograde and anterograde label included the ventromedial portion of the lateral division of the ventroposterior nucleus (VPL), which is known to represent the digits; the medial extent of a dorsal capping zone of VPL that we term the ventroposterior superior nucleus (VPS); and the anterior pulvinar (Pa). Cells labeled with one or the other tracer, as well as cells labeled with both tracers, were found in VPL, VPS, and Pa. Our procedures necessarily underestimated the numbers of cells projecting to both rostral and caudal injection zones, but at least 15-20% of VPL and 20-40% of VPS neurons that were autoradiographically labeled appeared to have such collaterals. While only a few cells in Pa were autoradiographically labeled from injections at the 3a-3b border, the presence of several double-labeled cells suggests that at least some Pa neurons project to both injected zones. By relating the present results to those from studies where connections were determined for single architectonic fields, we conclude that many neurons in VP project to both areas 3b and 1, and that many neurons in VPS project to both areas 3a and 2. In addition, both areas 3a and 2 appear to have interconnections with Pa. Connections of Pa with area 2 have only recently been reported (Pons and Kaas, in press), and connections of Pa with area 3a have not been described. The results imply that, in part, the same information from cutaneous receptors is relayed to areas 3b and 1, and the same information from deep receptors is relayed to areas 3a and 2.(ABSTRACT TRUNCATED AT 400 WORDS)