Biomedical subjects

H D Schwark

Publications and source records attributed to H D Schwark.

At least 19 recordsLinked to original sources

PubMed2001

Inflammatory pain reduces correlated activity in the dorsal column nuclei.

Persistent pain can result in sensitization of neurons in the spinal cord dorsal horn and produce physiological changes in sites such as the thalamus, that receive projections from the dorsal horn. Although the dorsal column nuclei receive both primary afferent input and projections from the dorsal horn, their participation in persistent pain states is relatively unexplored, perhaps because they play a limited role in acute, cutaneous nociception. We have used a model of inflammatory pain to examine the physiological properties of dorsal column nucleus neurons during persistent pain. We used this model in order to minimize direct damage to large myelinated primary afferents that project directly to the dorsal column nuclei. Inflammation was produced by injection of complete Freund's adjuvant into one hindpaw in rats, and neurons in the gracile nucleus were recorded 2-8 days later. Inflammation resulted in increased responsiveness to nociceptive (pinch) stimulation and increased incidence of afterdischarge firing 2-3 days after injection. Spontaneous activity was increased 6-8 days after injection. Inflammation decreased the strength of correlated firing in neuron pairs that shared common inputs, but did not affect the strength of monosynaptic interactions between neurons. These results suggest that the dorsal column nuclei can participate in persistent pain processes. Based on their anatomical connections, the dorsal column nuclei may contribute to thalamic changes during persistent pain as well as to supraspinal centers that modulate pain transmission in the spinal cord.

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PubMed2000

Distribution of neurons immunoreactive for calcium-binding proteins varies across areas of cat primary somatosensory cortex.

The primary somatosensory (SI) cortex in the cat contains four cytoarchitectonic areas that appear to contain separate body representations and have different functions. We tested whether functional differences among these areas are reflected in the densities of neurons containing each of three calcium-binding proteins: parvalbumin (PV), calbindin (CB), and calretinin (CR). Colocalization experiments revealed that CR was localized in a population of neurons distinct from those containing PV or CB. The general laminar distributions of the three calcium-binding proteins were similar to those described in other species and cortical areas, but there were significant density differences in layers II and III across SI. The density of PV-immunoreactive neurons was higher in areas 3b and 1 than in areas 3a and 2. CB-immunoreactive neurons were found in higher densities in anterior SI than in posterior SI, and the pattern of CR-immunoreactive neurons was reciprocal to that of CB, with significantly higher densities in posterior regions of SI. Since the firing characteristics of nonpyramidal neurons appear to be related to their calcium-binding protein content, differences in regional distributions of these neurons in layers II and III may contribute to functional differences between the cytoarchitectonic areas of SI cortex.

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PubMed1999

Inhibitory influences on receptive field size in the dorsal column nuclei.

Receptive fields (RFs) of neurons in the dorsal column nuclei (DCN) expand within minutes after the RFs are anesthetized via subcutaneous lidocaine injections (e.g., Pettit and Schwark). The mechanism of this rapid reorganization is of great interest. It has been proposed that such RF expansion results from a decline in inhibition within the DCN that unmasks previously ineffective synapses. To study the role of GABAergic inhibition in the DCN in controlling RF size, we applied by iontophoresis bicuculline methiodide to block gamma-aminobutyric acidA (GABA(A)) receptors and 2-OH-saclofen to block GABA(B) receptors. Blockade of GABA(A) receptors resulted in RF expansions in 79% of the neurons, while blockade of GABA(B) receptors resulted in RF expansions in 53% of the neurons. The effectiveness of receptor blockade in producing RF expansion was not related to neuronal response characteristics. Glutamate application resulted in RF expansions in only 2 of 23 neurons tested, suggesting that RF expansion was not simply due to increased excitability. The modality and adaptation characteristics of the expanded portions of the RFs were similar to those of the original RF. The results of the present study suggest that GABAergic inhibition can play a role in controlling RF size in the DCN, and that both GABA(A) and GABA(B) receptors may be involved in this process.

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PubMed1998

Distribution of substance P receptor binding in dorsal column nuclei of rat, cat, monkey and human.

In the present study, substance P receptor binding was localized in the dorsal column nuclei (DCN) of the rat, cat, monkey, and human. Bolton-Hunter-labeled [125I]substance P binding was most concentrated in the cell nests of the core region, but was present throughout the DCN of each species. The distribution of substance P receptors may reconcile apparent mismatches between the widespread responsiveness of DCN neurons to substance P and the restricted distribution of substance P containing afferents.

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PubMed1996

Capsaicin-induced rapid receptive field reorganization in cuneate neurons.

1. To determine whether activity in unmyelinated or thinly myelinated primary afferents affects the organization of cutaneous receptive fields (RFs) in the cuneate nucleus, subcutaneous injections of capsaicin were made into the RFs of cuneate neurons in anesthetized cats. The effects of capsaicin injection on RF size and position, response properties, and spontaneous firing rates were determined during single-unit recordings. 2. Subcutaneous injection of capsaicin (10% dissolved in 70% ethanol) into peripheral RFs produced rapid RF reorganization in all neurons tested (n = 20), even when the original RF remained responsive to tactile stimulation. RF reorganization was marked by the appearance of newly responsive RFs. These RFs appeared as either contiguous expansions of the original RF or as new, noncontiguous fields. Control injections of the vehicle alone never produced RF reorganization (n = 9). RF reorganization was not related to changes in spontaneous activity. 3. Following capsaicin-induced RF reorganization, subcutaneous injections of lidocaine were made into the original RFs (n = 8). These injections produced no additional RF reorganization in seven of the eight neurons, even though in each case the lidocaine injections produced at least partial blocks of responsiveness from within the original RF. 4. In approximately one-half of the neurons (9 of 20), the reorganized RFs had response properties that were different from those of the original RF. This result suggests that, for neurons in the dorsal column nuclei (DCN), physiological mechanisms that normally mask inputs and restrict RF size can give rise to response specificity. 5. The results of these experiments demonstrate that capsaicin-induced RF reorganization, which has been reported previously in ventrobasal thalamus and primary somatosensory cortex, can arise within the dorsal column-medial lemniscal system, at the level of the DCN. The present results also provide evidence that rapid RF reorganization in cuneate neurons can be produced by blockade of a subset of peripheral afferents that are sensitive to capsaicin.

Afferent Pathways↗

PubMed1994

Distribution and proportions of GABA-immunoreactive neurons in cat primary somatosensory cortex.

Certain receptive field properties of cortical neurons depend upon inhibitory, GABAergic inputs. In the somatosensory cortex, iontophoresis of bicuculline, a GABAA receptor blocker, results in enlargement of receptive fields. However, bicuculline's effectiveness in changing receptive field size varies with the neuron's adaptation characteristics, location within a particular submodality region, and laminar location. To test whether regional differences in the effectiveness of bicuculline are correlated with the distribution of cortical GABAergic neurons, we determined the numbers and proportions of GABA-immunoreactive [GABA(+)] neurons within cat primary somatosensory cortex. The laminar distribution of GABA(+) neurons was similar across all four cytoarchitectonic areas of primary somatosensory cortex, with layer II containing the highest areal density of GABA(+) neurons. Numerical proportions of GABA(+) neurons in the total neuron population were similar in areas 3b and 2 (29.8% and 22.6%, respectively). Laminar distributions of the proportions of GABA(+) neurons were also similar in these two areas; in both areas, layer I contained the highest proportion of GABA(+) neurons. The laminar distributions of GABA(+) neuron densities as well as GABA(+) neuron proportions differed from the reported laminar distribution of bicuculline effects on receptive field size. Moreover, within area 3b, these measures showed no evident patterns that might correspond to rapidly adapting and slowly adapting submodality regions.

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PubMed1994

Regional distribution of GABAA receptor binding sites in cat somatosensory and motor cortex.

Inhibition in primary sensory cortex plays a role in neuronal responses to peripheral stimuli. For many neurons in cat primary somatosensory cortex, blockade of GABAA receptors by bicuculline results in receptive field enlargement. The magnitude of this effect varies with the neuron's adaptation characteristics and its location in particular laminae and submodality regions. To test whether these variations are correlated with the distribution of GABAA receptors, we analyzed [3H]muscimol binding in cat primary somatosensory and motor cortical areas. The highest levels of binding were in layers I-III, and the lowest levels were in layers V-VI. In somatosensory cortical areas, layer IV was distinguished by higher levels of binding than in adjacent layers. Within layer IV, levels of binding were significantly higher in posterior area 3b than in anterior area 3b. These differences may correspond to the rapidly adapting and slowly adapting submodality regions which have been described in this area. The laminar distribution of [3H]muscimol binding differed from that of [3H]flunitrazepam, and neither resembled the distribution of the magnitude of bicuculline's effects on receptive field size. The laminar distribution of [3H]muscimol binding was highly correlated with the areal density of GABA-immunoreactive neurons described in a companion study.

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PubMed1994

Responses of rapidly adapting neurons in cat primary somatosensory cortex to constant-velocity mechanical stimulation.

1. The responses of rapidly adapting (RA) neurons to constant-velocity ramp stimulation were studied in the forepaw representation of primary somatosensory cortex (SI) of anesthetized cats. Single probe stimuli were used to indent the skin or to move hair parallel to the skin surface. The velocity of the moving stimulus probe was varied to determine the rate sensitivity of the neurons. 2. The cortical RA neurons were classified into four categories identified as G1/F1, Gint/Fint, G2/F2, and complex classes. The primary bases for classification in the present experiments were the pattern of response during ramp stimulation, velocity threshold, and directional sensitivity. 3. Of the RA neurons recorded in SI, 84% (49/58) could be assigned to one of the three response classes with little ambiguity. The remaining neurons showed more complex responses. The form of the complex responses suggested that they arose from a combination of inputs of different response classes. Some of these appeared to arise from a combination of different RA input classes, whereas others had components that resembled responses previously described for C mechanoreceptors. 4. Increased ramp velocity resulted in increased average firing frequency in 87% of the RA neurons. This relationship, which could be fitted with a power function, varied with response class. G1/F1 neurons were more sensitive to stimulus rate than G2/F2 neurons. Significant differences between response classes also were seen in the relationship between ramp velocity and their number of evoked action potentials and in their spontaneous firing rates. 5. The results demonstrate that a discrete SI neuron population is sensitive to the rate of stimulus movement. This observation is consistent with psychophysical studies reporting effects of stimulus indentation rates on perception of single probe stimuli. The appearance of complex responses in a small proportion of SI neurons provides evidence of convergence in somatosensory pathways to SI.

Afferent Pathways↗

PubMed1993

Receptive field reorganization in dorsal column nuclei during temporary denervation.

Altered sensory input can result in the reorganization of somatosensory maps in the cerebral cortex and thalamus, but the extent to which reorganization occurs at lower levels of the somatosensory system is unknown. In cat dorsal column nuclei (DCN), the injection of local anesthetic into the receptive fields of DCN neurons resulted in the emergence of a new receptive field in all 13 neurons studied. New receptive fields emerged rapidly (within minutes), sometimes accompanied by changes in adaptation rates and stimulus selectivity, suggesting that the new fields arose from the unmasking of previously ineffective inputs. Receptive field reorganization was not imposed by descending cortical inputs to the DCN, because comparable results were obtained in 10 additional cells when the somatosensory and motor cortex were removed before recording. These results suggest that mechanisms underlying somatotopic reorganization exist at the earliest stages of somatosensory processing. Such mechanisms may participate in adaptive responses of the nervous system to injury or continuously changing sensory stimulation.

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PubMed1993

Distribution of [3H]QNB and [125I]alpha-bungarotoxin binding and acetylcholinesterase activity in visual system and hippocampal structures of eleven mammalian species.

This study assessed interspecies differences in regional brain distribution of [3H]QNB binding, [125I]alpha-bungarotoxin binding and acetylcholinesterase activity, by autoradiographic and histochemical methods. Eleven mammalian species were examined, including carnivores (cat, dog), a lagomorph (rabbit), and rodents (squirrel, guinea pig, gerbil, hamster, vole, lemming, rat, mouse). Comparisons were based on primary visual system structures (superior colliculus, lateral geniculate nucleus, primary visual cortex) and the hippocampal formation. The two radioligands differed greatly in the degree of interspecies variation: while the pattern of [3H]QNB binding was quite similar across species, [125I]alpha-bungarotoxin showed striking interspecies diversity. This contrast was most obvious in laminar patterns of the visual cortex and hippocampal formation. Regional distributions of acetylcholinesterase staining were fairly diverse, and were unlike the patterns of either [3H]QNB or [125I]alpha-bungarotoxin. The two ligands showed more consistency in overall levels across species than did acetylcholinesterase. Possible correlates of the differences in interspecies diversity are discussed.

Acetylcholinesterase↗

PubMed1992

Corticocortical connections of cat primary somatosensory cortex.

The organization of corticocortical connections in the representation of the forepaw in cat primary somatosensory cortex (SI) was studied following injections of various tracers into different cortical cytoarchitectonic areas. Small injections of horseradish peroxidase, wheat germ agglutinin-conjugated HRP, Phaseolus vulgaris leukoagglutinin, or fast blue were placed into the representation of the forepaw in areas 3b, 1, or 2. The positions of labeled neurons in SI and the surrounding cortical areas were plotted on flattened surface reconstructions to determine the organization of the corticocortical connections within SI. A strong, reciprocal projection linked the two forepaw representations which have been described in area 3b and the part of area 2 which lies in the anterior bank of the lateral ansate sulcus (see Iwamura and Tanaka 1978a, b). Dense projections also linked these areas with SII, as previously reported (Burton and Kopf 1984a). Additional projections to area 3b arose primarily from areas 3a and 1. Projections to area 2 were more widespread than those to area 3b, and arose from all other areas of SI as well as from areas 4 and 5a. All injections into SI tended to label groups of neurons which lay in mediolateral strips. Corticocortical projection neurons which were most heavily labeled by SI injections were pyramidal cells in layer III. Additional projections from area 2 to 3b, area 5a to 2, and SII to areas 2 and 3b arose from layer VI as well. Although neurons of layers III and VI were always the most densely labeled, large injections into SI labeled neurons in layers II and V as well.

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PubMed1989

The distribution of intrinsic cortical axons in area 3b of cat primary somatosensory cortex.

The morphology of single neurons in area 3b of cat primary somatosensory (SI) cortex was examined after horseradish peroxidase (HRP) injections. Neurons were labeled either by intracellular injection of HRP following intracellular recording or by small extracellular iontophoretic HRP injections. Both pyramidal and nonpyramidal neurons were labeled and reconstructed from serial sections. Their axons had local, interlaminar and interareal patterns of termination. Most neurons formed local axonal fields around their cell bodies and dendrites. Pyramidal neurons in cortical layer IV sent axons up into layers II and III, neurons in layers II and III sent axons down to layer V, and layer V neurons sent axons to layer VI as well as back to the upper layers. Layer VI neurons sent axons back to the upper cortical layers in a unique bowl-shaped pattern. The horizontal distribution of axons of pyramidal cells in layer III was extremely widespread. Axons of layer III neurons in area 3b terminated within 3b and area 1, but not in other areas of SI. Layer III neurons in area 1 distributed axon collaterals to all fields of SI as well as projecting a main axon to motor cortex. In general, the axon collaterals of area 3b pyramidal cells outside layer III remained confined to area 3b. Most of the nonpyramidal neurons labeled were basket cells in layers III and VI. These neurons formed dense axonal fields around their cell bodies, and none of their axons could be followed into the underlying white matter. The results of the present study demonstrate that area 3b somatosensory cortical neurons and their axons are vertically organized in a manner similar to that reported for other sensory cortical areas. They also show that widespread horizontal connections are formed by pyramidal neurons of layer III, and that these horizontal axons can travel for great distances in the cortical grey matter.

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PubMed1988

Morphology of physiologically characterized medial lemniscal axons terminating in cat ventral posterior thalamic nucleus.

1. Medial lemniscal axons were identified by extra- and intracellular recording in the thalamic ventral posterior lateral nucleus (VPL) of cats and injected intracellularly with horseradish peroxidase (HRP). 2. Axons were characterized in terms of their latencies of response to stimulation of the medial lemniscus in the medulla, their receptive fields, and the temporal patterns of their discharge in response to stimulation of the receptive field with natural, hand-held stimuli. One-hundred sixty-six axons were placed in five operational groups: hair transient (Ht) (n = 41); hair sustained (Hs) (n = 45); pressure transient (Pt) (n = 14); pressure sustained (Ps) (n = 27), and deep or joint (Jt) (n = 39). 3. There was a tendency for Jt axons to have their terminations in anterodorsal parts of VPL and for those in the four cutaneous categories to have theirs in more central parts of the nucleus. 4. Nineteen injected axons with receptive fields mainly on the distal forelimb were subjected to detailed morphological analysis in terms of extent of terminal field and number of boutons. All axons ended in localized terminal fields that were more extensive anteroposteriorly than in the other dimensions. All showed an overall similarity and similar ranges of variation. There was a tendency, however, for Jt axons to have the least extensive terminations with fewest boutons. Ps axons had the most extensive terminations and largest number of boutons; Hs axons had small terminations and few boutons but Ht axons had small-to-medium arborizations with many boutons; no Pt axons were sufficiently well stained to enable comparisons of them with the others. There were no marked differences in axon diameter or conduction velocity among the five types. 5. Boutons identified light microscopically tended to be clustered in linear chains along proximal dendrites of relay neurons and electron microscopy revealed that they were terminals making synaptic contacts on relay cell dendrites and on presynaptic dendrites of interneurons. 6. These results reveal more similarities than differences among lemniscal axon terminations in VPL. Further studies of a quantitative nature on stimulus-response coupling and on the geographic distribution of lemniscal synapses on relay neurons will be required to reveal how lemniscal input is translated into relay cell output in VPL.

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PubMed1987

Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex.

The number and proportion of neurons displaying GABA immunoreactivity were determined for 50-micron-wide columns through the thickness of 10 areas of monkey cerebral cortex, including the precentral motor area (area 4), 3 cytoarchitectonic fields of the first somatic sensory area (areas 3b, 1, and 2), 2 areas of parietal association cortex (areas 5 and 7), the first and second visual areas (areas 17 and 18), area 21 of the temporal lobe, and areas of the orbital and lateral frontal cortex. Methods of fixation and immunocytochemical processing were designed to maximize the number of stained cells in 15-micron-thick frozen sections and 1-micron-thick plastic sections. In 8 of the 10 areas the number and proportion of GABA-immunoreactive neurons per 50-micron-wide column were found to be the same (34-43 cells/column; 25% of the total neuronal population). Areas 17 and 3b differed. Area 17 contained 50% more GABA-immunoreactive neurons (52-66 cells/column) but more than twice the total number of neurons, so that the GABA cells made up less than 20% of the total. In 3 monkeys, the number and proportion of GABA-positive neurons per 50-micron-wide column in area 3b were smaller than in adjacent areas of sensorimotor cortex (26-42 cells/column; 19-22%). In 2 other monkeys, the number and proportion (34-43 cells/column; 24-26%) were the same as in adjacent areas. Despite the similarity among most areas of monkey cortex, within some areas, the number of GABA-positive neurons per 50-micron-wide column varied as much as 30%. These variations form a significant, repeating pattern only in area 18, where narrow bands (150-200 micron wide) of relatively few stained cells alternated with either narrow or wide bands (600-700 micron wide) in which columns contained more cells. The GABA-immunoreactive neurons were unevenly distributed across layers, with every area containing large numbers and proportions of stained cells in layer II, and every area but area 4 displaying a second concentration in the principal thalamocortical recipient layers. In area 4, the number of GABA-positive neurons declined sharply from layer II to layer III and remained low through layer VI. For areas displaying the greatest intra-areal variability, only 1 or 2 layers contributed significantly to that variability (layer IV in area 3b, layers III and V in area 18, and layers II and III in area 17).(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1986

Extent of the ipsilateral representation in the ventral posterior medial nucleus of the monkey thalamus.

Single and multiunit mapping was used to determine the extent of the representation of ipsilateral structures in the ventral posterior medial (VPM) nucleus of the thalamus in cynomolgus monkeys. The extent of the VPM occupied by terminations of afferent fibers arising in the ipsilateral principal trigeminal nucleus was also determined by anterograde transport of horseradish peroxidase. Both methods indicate that most of the medial half of VPM is occupied by the ipsilateral representation. This is much larger than previously suspected. Units in the medial half of VPM have small, well localized receptive fields on the ipsilateral side of the lower lip, tongue and palate, in the ipsilateral cheek pouch and on the ipsilateral teeth. The representation is largest for the ipsilateral side of the tongue and the cheek pouch. Most units in the lateral half of VPM have small, contralateral receptive fields. Few units in VPM have bilateral receptive fields. VPM is clearly distinguishable by cytochrome oxidase (CO) staining. Anteroposteriorly elongated, CO-positive aggregations correspond to elongated aggregations of units with the same or closely similar receptive fields, especially in the medial, ipsilateral representation.

Animals↗

PubMed1986

Cat area 17. I. Pattern of thalamic control of cortical layers.

Reversible inactivation of individual layers of the cat lateral geniculate and medial interlaminar nuclei was used to investigate the necessary and sufficient inputs for maintaining visually driven activity and receptive field properties in area 17. Neither orientation selectivity nor direction selectivity depends on any individual geniculate layer. We identified two groups of cortical layers on the basis of the pattern of thalamic inputs providing visual driving through the contralateral eye. One group, consisting of layers 4 and 6, has geniculate layer A as its only necessary and sufficient input. The other, consisting of supragranular layers, integrates at least two sufficient thalamic inputs, one of which is layer A. Several major receptive field properties are independently generated in these two groups of layers.

Animals↗

PubMed1986

Cat area 17. II. Response properties of infragranular layer neurons in the absence of supragranular layer activity.

Response properties of cells in the infragranular layers of cortical area 17 of the cat were examined in the absence of input from supragranular layers. Supragranular activity was silenced either reversibly by cooling the surface of cortex or permanently by making a cryogenic lesion of the supragranular layers. Visually driven responses of cells throughout the cortical column were recorded with a linear array of electrodes. Most infragranular layer cells continued to be visually responsive in the absence of supragranular layer input. These cells were similar to normal infragranular layer cells on measures of visual responsiveness, orientation selectivity, and direction selectivity. Special complex, but not standard complex, cells were absent in layer 5 when supragranular layers were destroyed. We found no evidence for a selective effect of removal of supragranular activity on the response properties of cells in layer 6. We propose that the intracolumnar projection from the supragranular layers drives the special complex cells of layer 5, but is not necessary for the visual driving of most other infragranular layer cells. This projection does not impose selectivity for stimulus orientation or direction on the remaining active cells of the infragranular layers.

Animals↗

PubMed1986

Cat area 17. III. Response properties and orientation anisotropies of corticotectal cells.

The receptive field properties of antidromically identified corticotectal (CT) cells in area 17 were explored in the paralyzed, anesthetized cat. To compare these with another population of infragranular cells, we also examined the receptive field properties of cells in layer 6. Sixty percent of our sample of CT cells showed increased response to increased stimulus length (length summation) and were classified as standard complex cells. The other 40% showed little or no length summation, were generally end stopped, and were classified as special complex cells. Standard and special complex CT cells have complementary orientation anisotropies: the distribution of orientation preferences of standard complex cells is biased toward obliquely oriented stimuli, whereas special complex cells are biased toward horizontally and vertically oriented stimuli. The receptive fields of the cells in our sample were primarily along the horizontal meridian so we cannot determine if these anisotropies are defined relative to the vertical meridian or relative to the meridian passing through the receptive field. The effects of these anisotropies in preferred orientation are minimized by the broad orientation tuning of CT cells. There was no simple relationship between the direction bias of CT cells and the reported direction bias of tectal cells. In contrast to the heterogeneity of corticotectal cells, layer 6 cells uniformly showed strong length summation, tight orientation tuning, and little spontaneous activity.

Animals↗