Biomedical subjects

P J Snow

Publications and source records attributed to P J Snow.

At least 19 recordsLinked to original sources

PubMed1992

Expression of lectin binding in the superficial dorsal horn of the rat spinal cord during pre- and postnatal development.

The plant lectin Bandeiraea simplicifolia I-B4 binds to the soma and central terminals of a subpopulation of unmyelinated primary sensory neurones in the adult rat. The binding site of this lectin is thought to be the terminal alpha-D-galactose residue of a membrane associated glycoconjugate which may be involved in the development of specific connections between small diameter primary sensory neurones and second order neurones in the superficial dorsal horn of the spinal cord. To begin to investigate this possibility we have examined the development of lectin binding in the dorsal horn of pre- and postnatal rats. Lectin binding first appeared on axon profiles in the superficial dorsal horn of the spinal cord at embryonic days 18/19. Previous studies in the rat have revealed that the central processes of small diameter primary sensory neurones enter the dorsal horn at embryonic days 18/19. Our findings suggest that the glycoconjugate to which this lectin binds, is expressed by the central processes of small diameter primary sensory neurones as they grow into the spinal cord. It is therefore possible that this glycoconjugate is involved in the development of topographically ordered neural connections within the dorsal horn of the spinal cord.

Animals↗

PubMed1992

The representation of prolonged and intense, noxious somatic and visceral stimuli in the ventrolateral orbital cortex of the cat.

The responses of single neurones in the ventrolateral orbital (VLO) cortex to noxious pinch, heating of the skin, twisting of the joints and distension of the gall bladder were studied in cats anaesthetized with halothane. Of 60 neurones studied, 44 responded to prolonged (greater than 10 sec) stimuli that were well within the noxious range. Neurones were relatively unresponsive to innocuous stimuli or to the transient application of noxious stimuli. Many single neurones responded to a variety of modalities of noxious stimuli (e.g., skin heating and gall bladder distension). Many neurones studied showed a fluctuating level (5-15 Hz) of ongoing spontaneous activity. Neurones responded with either an increased frequency of spikes (excitation) or an inhibition of spontaneous discharge, irrespective of the source of noxious stimulation. Noxious stimuli delivered simultaneously to two different tissues (e.g., skin and visceral) sometimes produced excitation of the neurone under study, to levels above that produced by the application a noxious stimulus to only one of the tissues. Receptive fields were often large involving both contralateral and ipsilateral areas of the body, as well as both fore and hind limbs. No evidence of somatotopic organization was obtained. The responses of some neurones outlasted the application of the stimuli by many minutes. It is concluded that single neurones in the ventrolateral orbital cortex respond to the prolonged application of intensely noxious stimuli to a variety of body tissues, in a manner that is in keeping with the involvement of this cortical area in both the physiological, autonomic and experiential components of the affective-motivational aspect of pain. Furthermore, from the consequences of lesion studies in man and animals, it is proposed that the activation of cells in the orbital cortex by a variety of noxious stimuli reflects its more general role in the development and maintenance of behaviour in response to negative reinforcement of both social and physical origins.

Animals↗

PubMed1991

Effect of neonatal denervation of hindlimb digits on the somatotopic organization of lumbar spinocervical tract neurons in the cat.

1. The effect of transection and ligation of the digital nerves of either one (toe 3) or two (toe 3 and toe 4) hindpaw digits, in the first postnatal week, on the tactile receptive fields (RFs) of spinocervical tract (SCT) neurons was studied in adult, alpha-chloralose-anesthetized cats. Immediately before recording, the digital nerves of the corresponding digit(s) of the opposite, intact hindpaw were transected, and the neonatally lesioned digital nerves were recut proximal to the transection neuroma. 2. In the medial part of the dorsal horn at the L6-L7 level, the digits of the hindlimb are represented in the RFs of SCT cells in a precise axial sequence from the most medial digit (toe 2) rostrally to the most lateral digit (toe 5) caudally. Acute denervation of one or two digits in the adult produced an area in the ipsilateral dorsal horn in which SCT cells lacked any RFs. When acute denervation was restricted to a single digit, the unresponsive region of dorsal horn was approximately 3 mm in length, and when two digits were denervated the unresponsive zone was approximately 6 mm long. Because the representation of the toes of the left hindpaw is a mirror image of that of the right, the rostrocaudal extent and position of the region of unresponsive SCT cells was used to assess the location of the borders of the chronically deprived region on the opposite side of the cord. 3. In all cats examined after neonatal denervation of toe 3, most (89%) of the SCT cells sampled within the chronically deprived toe 3 representation had RFs. These RFs were either on toe 2 (44%) or toe 4 (18%), and a large proportion of cells (38%) had multiple RFs with components on both toe 2 and toe 4. In most cases the cells fired briskly to displacement of hairs or light touch of the skin within these RFs. SCT cells with a RF on toe 2 and/or toe 4 were found throughout the whole 3-mm length of the chronically deprived toe 3 region, but cells with a RF on toe 2 were more commonly found than cells with a RF on toe 4 at axial distances greater than or equal to 1.5 mm from the boundary of the normal representations of the respective digit. 4. After chronic, neonatal denervation of both toe 3 and toe 4, 59% of SCT cells sampled overall had RFs, but there was a large degree of interanimal variation in the proportion of unresponsive neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Organization of the spinal cord in four species of elasmobranch fish: cytoarchitecture and distribution of serotonin and selected neuropeptides.

An analysis of Nissl stained sections of the spinal cord taken from four species of elasmobranch showed that seven distinct cytoarchitectonic laminae are present. These laminae are compared with laminae described previously in the spinal cord of other vertebrates. The distribution of immunoreactivity to serotonin, substance P, somatostatin, calcitonin gene-related peptide, neuropeptide Y, and bombesin was determined in the brown stringray (Dasyatis fluviorum), the eagle ray (Aetobatis narinari), the shovelnose ray (Rhinobatis battilum), and the black-tip shark (Carcharhinus melanopterus). In all species, dense immunoreactivity to most substances tested was found in the outer part of the substantia gelatinosa. Many fibres and varicosities immunoreactive to substance P, calcitonin gene-related peptide, and bombesin were found in this region and smaller numbers of fibres were found in the nucleus proprius. Immunoreactivity to somatostatin consisted of coarse fibre bundles that entered the dorsal horn at the nucleus proprius and radiated dorsally to the substantia gelatinosa. Axons and varicosities immunoreactive to serotonin and neuropeptide Y were found in all regions of the dorsal horn but were concentrated in the outer part of the substantia gelatinosa. The distribution of immunoreactivity to met-enkephalin in the shovelnose ray was concentrated in the lateral third of the substantia gelatinosa and to a lesser extent in the nucleus proprius. The distribution of these substances is compared with that described in other vertebrates. Although the sensory information reaching the elasmobranch spinal cord is limited, compared with that of mammalian species, the distribution of these neuroactive factors in the dorsal horn of the two groups is strikingly similar.

Animals↗

PubMed1990

The effect of peripheral nerve section on lectin binding in the superficial dorsal horn of the rat spinal cord.

The effect of peripheral nerve section on binding of the plant lectin soybean agglutinin (SBA) to the dorsal horn of the spinal cord has been investigated in the rat. Four, 15 and 43 days after unilateral sciatic nerve section no effect on SBA binding in the L4 segment of the spinal cord was apparent. However 90 days after nerve section a marked decline in SBA binding was observed. It is suggested that the long latency in effect on SBA binding may be due to the slow rate of utilisation of the SBA binding site.

Acid Phosphatase↗

PubMed1990

Peptide coexistence in axon terminals within the superficial dorsal horn of the rat spinal cord.

The somata of primary sensory neurons have been shown to contain up to four (and possibly more) neuroactive peptides. Although each of these peptides has been separately located in axon terminals within the superficial dorsal horn of the spinal cord, it is not clear whether multiple peptide coexistence is also a feature of terminal varicosities. The aim of this study was to determine whether the peptides substance P (SP) and calcitonin gene-related peptide (CGRP), which are colocalized in the somata of a large number of primary sensory neurons, coexist in the central terminals of these neurons in the spinal cord. The protein A-gold technique of antigen localization was used to screen single boutons in laminae I and II of the rats spinal cord for SP- and CGRP-like immunoreactivity at the ultrastructural level. The results show that SP and CGRP are colocalized within a large number of synaptic boutons in the superficial dorsal horn. Furthermore, evidence was obtained to suggest that both SP and CGRP may be found in the same synaptic vesicle within these boutons. These findings indicate that both SP and CGRP may be coreleased from single terminals in the superficial dorsal horn. This is of considerable interest in view of the reported interaction between SP and CGRP in nociceptive behavioral responses in the rat.

Animals↗

PubMed1989

The plant lectin soybean agglutinin binds to the soma, axon and central terminals of a subpopulation of small-diameter primary sensory neurons in the rat and cat.

The distribution of binding of the plant lectin soybean agglutinin to primary sensory neurons has been investigated in the rat and cat. Soybean agglutinin was found to bind to approximately 30% of neurons in the fourth, lumbar dorsal root ganglion of the rat and approximately 50% of neurons in the first, sacral dorsal root ganglion in the cat. Morphometric analysis of these dorsal root ganglia revealed that in both species those neurons which bind soybean agglutinin appear to be a subpopulation of the small-diameter cells. Electron microscopic analysis of the lumbar dorsal roots revealed that soybean agglutinin binds to the plasma membrane of a subpopulation of unmyelinated axons in both species. Myelinated axons did not bind the lectin. In the dorsal horn of the spinal cord, soybean agglutinin bound to components of Lissauer's tract and the superficial laminae (laminae I and II) of the dorsal horn in both species. In the dorsal horn lectin binding was limited to lamina I and the outer portion of lamina II (sublamina IIo) in the cat, while in the rat lamina I and the entire dorsoventral extent of lamina II (sublaminae IIo and IIi) were labelled. Thirty days following dorsal rhizotomy, soybean agglutinin binding in the superficial dorsal horn, ipsilateral to the rhizotomy, was abolished in both species. These results show the plant lectin soybean agglutinin to be a histochemical marker for the soma and central terminals of a subpopulation of small-diameter sensory neurons in both the rat and cat. It is suggested that soybean agglutinin binding may be used in conjunction with immunohistochemistry to allow identification of putative neurotransmitters within, or in synaptic profiles associated with, the central terminals of small-diameter primary sensory neurons.

Animals↗

PubMed1988

Soybean agglutinin binds to a subpopulation of primary sensory neurones in the cat.

The binding of the plant lectin soybean agglutinin (SBA) to primary sensory neurones has been investigated in the rat. SBA binding was found in Lissauer's tract and in laminae I and IIo of the dorsal horn at cervical, thoracic and lumbar levels. Morphometric analysis of the S1 dorsal root ganglia revealed that SBA binding was associated with the small diameter cell population, considered to be the cell bodies of unmyelinated afferent fibres (C-fibres). These findings suggest that SBA may be a useful ultrastructural marker for C-fibre terminals.

Animals↗

PubMed1988

Somatotopic organization of the dorsal horn in the lumbosacral enlargement of the spinal cord in the neonatal cat.

The somatotopic organization of the light touch receptive fields of single unidentified dorsal horn neurons in the lumbosacral spinal cord has been studied in the neonatal cat anesthetized with chloralose. Satisfactory recordings were obtained from single dorsal horn neurons in kittens aged 3-6 days. Reconstruction of recording tracks from pontamine blue dye spots and comparisons of the depths of recording sites with Nissl-stained sections of cord showed that most single-unit recordings were obtained from laminae III and IV of Rexed. In animals of all ages neurons were found which responded briskly to light cutaneous mechanical stimulation. Their receptive fields varied widely in size, being smallest on the distal digits and largest on proximal skin. Receptive field areas were similar in proportion to the size of the hindlimb to those seen in the equivalent region in the adult cat. Because of the shape of the dorsal horn and the relatively narrow dorsal columns in neonatal kittens it proved difficult to locate units with receptive fields on proximal skin. Nevertheless the main features of the somatotopic organization of the dorsal horn were similar to those in the adult cat. Thus the somatotopic map of the kitten showed a medial representation of glabrous skin that was bounded laterally by the representation of the hairy skin of the toes. Proximal skin was represented in the lateral parts of the dorsal horn, a region which was not easily accessible for microelectrode recording. The individual toes were represented in a rostral to caudal sequence such that toe 2 was represented rostrally and toe 5 caudally. Around the toe representation the medial surface of the foot was represented rostrally, the ventrolateral surface caudally, and the dorsal surface laterally. The results indicate that the mature organization of light touch receptive fields of dorsal horn neurons in the lumbosacral cord of the cat is already largely present at birth.

Action Potentials↗

PubMed1988

The coexistence of neuropeptides in feline sensory neurons.

The coexistence of immunoreactivity to the peptides substance P, bombesin, calcitonin gene-related peptide and somatostatin has been determined in single, lumbar and sacral dorsal root ganglion cells in the cat. Colchicine pretreated L7 and S1 dorsal root ganglia were embedded in wax and cut into 5 microns sections. Groups of four, serially adjacent sections were reacted with antisera to one of four peptides using avidin-biotin immunocytochemistry. It was thus possible to determine the coincidence of the four peptides in single cell bodies by examining the immunoreactivity in a ganglion cell in one section and then locating the same cell in three adjacent sections. As a comparison, this procedure was repeated on a different population of ganglion cells using antiserum to substance P, bombesin and calcitonin gene-related peptide only. The results indicate that different combinations of three or four peptides may occur in single, small diameter sensory neurons in the cat. It would appear that immunoreactivity to bombesin and/or calcitonin gene-related peptide coexists with immunoreactivity to substance P in some dorsal root ganglion cells. However, immunoreactivity to each of these peptides was also found to occur alone in single cells. Immunoreactivity to calcitonin gene-related peptide but not to the other three peptides was found to occur in some medium-sized cell bodies (up to 70 microns). Somatostatin-like immunoreactivity was found to have a high level of coexistence with substance P-like immunoreactivity in cells which contained immunoreactivity to these two peptides only. Immunoreactivity to all the four peptides tested was found to occur in 18-26% of ganglion cells which contained at least one peptide.

Animals↗

PubMed1988

Somatotopically inappropriate projections from thalamocortical neurons to the SI cortex of the cat demonstrated by the use of intracortical microstimulation.

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.

Action Potentials↗

PubMed1987

Response of lumbar spinocervical tract cells to natural and electrical stimulation of the hindlimb footpads in cats.

Extracellular and intracellular recordings were made from antidromically identified spinocervical tract (SCT) cells in the medial part of the lumbosacral dorsal horn in anesthetized cats. The low threshold mechanoreceptive fields (RFs) of 18 cells were mapped during extracellular recording, and for 15 the RF included an area of glabrous skin. Intracellular recordings were made from 6 of these during electrical microstimulation of glabrous skin and all showed excitatory postsynaptic potentials at latencies consistent with conduction over group II primary afferent fibers. The distance from the medial border of the dorsal horn of the recording loci of 12 cells, 4 of which were injected with horseradish peroxidase, was measured. It is concluded that some medially situated SCT cells receive excitatory input from low threshold group II primary afferent fibers from glabrous skin.

Animals↗

PubMed1987

Reorganization of the receptive fields of spinocervical tract neurons following denervation of a single digit in the cat.

The effect of acute and chronic section of the digital nerves of a single toe on the organization of low-threshold, mechanoreceptive fields of lumbosacral spinocervical tract (SCT) neurons has been studied in adult cats anesthetized with chloralose. The immediate effect of sectioning the digital nerves of a single toe is to produce a patch of dorsal horn in the medial region of the ipsilateral lumbosacral cord in which SCT neurons lack any peripheral receptive field when gentle hair movement or light touch of glabrous skin are used as stimuli. Other SCT neurons in the region may lose only part of their receptive fields. Between 30 and 70 days later most of the affected SCT neurons have established receptive fields. These are mainly on somatotopically inappropriate areas of skin medially and laterally adjacent to the denervated region. A small proportion of SCT neurons form discontinuous receptive fields. The relative somatotopic organization within the affected region remains unchanged. As there is no sign of regeneration of the sectioned nerves the new receptive fields must result from a central reorganization of excitatory inputs to SCT neurons. It is concluded that chronic peripheral nerve section affects the anatomical and physiological mechanisms underlying the formation of light touch receptive fields of dorsal horn neurons in the lumbosacral cord of the adult cat, but that the resulting reorganization of receptive fields is spatially restricted.

Animals↗

PubMed1986

The electrophysiological and morphological characteristics of feline dorsal root ganglion cells.

The electrophysiological characteristics of physiologically typed L7 and S1 dorsal root ganglion (DRG) cells have been studied in the cat by intracellular recording. The injection of the fluorescent dye Lucifer Yellow has enabled us to study the morphology of these neurons. Our results show that over the entire range of primary sensory afferents there is a linear relationship between the peak rate of rise of somatic action potentials (dv/dt) and axonal conduction velocity. There is a prominent inflexion on the repolarizing phase of the somatic action potentials of group III and group IV afferents. This is not seen in the action potentials of group II or group I afferents. These results correlate with the observation that the total action potential duration (APD) is inversely related to conduction velocity. Primary afferent somata were observed to have an ellipsoidal shape with the long axis in the rostrocaudal dimension. It was observed that for all afferents studied the volume of a dorsal root ganglion cell was linearly related to its peripheral axonal conduction velocity. We were able to show further that group IV somata, some of whose axons supplied nociceptors, were among the smallest in the ganglion.

Action Potentials↗

PubMed1986

The detailed somatotopic organization of the dorsal horn in the lumbosacral enlargement of the cat spinal cord.

The somatotopic organization of spinocervical tract cells and unidentified dorsal horn neurons that lie in the same depth range as the spinocervical tract cells has been examined in detail in the lumbosacral enlargement of cats anesthetized with alpha-chloralose. Only gentle hair movement or light touch of glabrous skin were used as stimuli. Within the region of the dorsal horn containing these neurons there is a precise somatotopic organization. However, there is considerable variation between animals in the relationship between the somatotopic map and the lumbosacral segmental boundaries. The somatotopic map described here is considered to be restricted to a 300- to 500-micron thick lamina. In the medial half to two-thirds of this lamina in the L6 and L7 segments the toes are represented in a rostrocaudal sequence from toe 2 to toe 5. Over the most medial 200-500 micron of this part of the dorsal horn are found cells that respond to stimulation of the glabrous skin of the toe pads and the central pad. The toe representation is surrounded by a strip of foot representation, which is in turn surrounded by a strip of leg representation. The most lateral part of the lamina curves ventrally in the L6 and L7 segments and contains a continuous rostrocaudal representation of the skin of the thigh. In this region are found both spinocervical tract cells and unidentified dorsal horn neurons with receptive fields on the thigh. The skin of the hindlimb is represented such that a line of discontinuity runs down the posteromedial thigh, leg, and foot. Skin lateral to this line is represented caudally, while skin medial to it is represented rostrally.

Afferent Pathways↗

PubMed1986

Distribution of activity in the spinal terminations of single hair follicle afferent fibers to somatotopically identified regions of the cat spinal cord.

Single-unit spike-triggered averaging has been used to study the distribution of activity in the central processes of 11 single hair follicle afferent (HFA) fibers in relation to the somatotopic organization of dorsal horn neurons (DHNs). Central responses could be recorded from all but one HFA, and the waveforms of these responses were similar to the biphasic, monophasic positive and compound terminal potentials (TPs), the triphasic, positive-negative-positive axonal (preterminal) potentials (APs), and the focal synaptic potentials (FSPs) described by other workers in different preparations. No central responses could be recorded from one HFA even though this axon was shown to be intact throughout the experiment and noise levels in the averaged records were below 3.1 microV. The spatial organization of TPs and APs mirrored the anatomical organization determined using intraaxonal staining only in that the region containing these potentials was a longitudinally orientated narrow (mean width = 405 microns) strip of dorsal horn. Within this strip large TPs, APs, and FSPs were usually found only in those regions in which the receptive field (RF) of the HFA was relatively central to the RFs of DHNs. The region in which the RFs of DHNs encompassed the RF of the HFA, the somatotopically appropriate region, was also organized into a longitudinally orientated strip of dorsal horn of approximately the same width as the strip containing TPs and APs. In any single experiment the strips formed by the somatotopically appropriate region and the TP-AP region occupied the same mediolateral position, but in contrast, the rostral and/or caudal boundaries of these strips often occurred at different levels along the dorsal horn. In some cases the TP-AP strip extended rostrally and/or caudally beyond the somatotopically appropriate region or ended at the same rostrocaudal level. In other cases the somatotopically appropriate region extended rostrally and/or caudally beyond the TP-AP strip. These results are discussed in relation to the rostrocaudal spread of the dendritic trees and the RF organization of DHNs. The results show clearly that in intact cats, anesthetized with alpha-chloralose, some HFAs give rise to collaterals in somatotopically inappropriate regions of the dorsal horn and that at least some parts of these collaterals are invaded by incoming action potentials. The question of whether some HFAs give rise to collaterals that are either infrequently invaded or not invaded at all is discussed.

Animals↗

PubMed1985

Neuropeptides in physiologically identified mammalian sensory neurones.

In cats, intracellular dye injection of single sensory neurones of known fibre type and sensory modality has been combined with peptide immunohistochemistry. There was no clear relationship between the sensory function of a neurone and the presence of the neuropeptides substance P, somatostatin, cholecystokinin and vasoactive intestinal polypeptide, in its cytoplasm. In particular, substance P was not detected in many nociceptive sensory neurons even though it could be demonstrated with the same technique in many sensory neurones which did not have cutaneous receptive fields. These results mean that the role, if any, of these neuropeptides in the transmission of pain, must be regarded as complex.

Animals↗

PubMed1985

Coexistence of peptide immunoreactivity in sensory neurons of the cat.

The coexistence of the neuropeptides substance P, cholecystokinin, somatostatin and vasoactive intestinal polypeptide in cat sensory neurons has been examined using peroxidase-anti-peroxidase immunocytochemistry. Attempts were also made to locate cells containing bombesin, neurotensin, [Met]enkephalin and [Leu]enkephalin but no immunoreactivity was found when antisera to these peptides was used. Cells in the dorsal root ganglia were studied by cutting 5 microns serial wax sections or 15 microns cryostat sections. Coexistence was established by applying the antiserum to each peptide to serially adjacent 5 microns sections and establishing the presence of peptide-like immunoreactivity in each of 4 different sections through a single cell. Results showed that the distribution and combinations of coexistence of these neuropeptides in the cat is extremely complex; three and sometimes all four antisera showing immunoreactivity with a single cell. About 21% of all ganglion cells contained some immunoreactivity but there were certainly some small cells which did not contain any immunoreactivity. The coexistence of these peptides differed markedly from that previously reported in the rat suggesting that interspecific differences in the neuropeptide content of cells might be much greater than they are for classical neurotransmitters. The results are discussed in relation to the possible role of neuropeptides and the regulation of their production by sensory neurons.

Animals↗