Influence of psychosocial factors on survival of home-dialysis patients.
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Biomedical subjects
Publications and source records attributed to H Burton.
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The central projections of afferent fibers from the cornea, and the infraorbital, infratrochlear, frontal, lacrimal and auriculotemporal nerves were investigated by means of the transganglionic transport of horseradish peroxidase. Afferent projections to the dorsal horn of the medulla are organized along both the rostrocaudal axis and the ventrolateral to dorsomedial margin of the medullary dorsal horn. An inverted but discontinuous facial representation exists through the restrocaudal axis of the dorsal horn of the medulla with perioral and nasal receptive fields innervated by the infratrochlear nerves represented rostral to the progressively more posterior receptive fields innervated by the frontal, lacrimal and auriculotemporal nerves, respectively. The organization of the primary afferents is not uniform over the laminae of the dorsal horn of the medulla; the projections from the different nerves show the least overlap in lamina II, while overlap is most extensive in laminae I and V. The sensory projection from the cornea to the medullary dorsal horn is most dense in laminae I and II. All nerves, including those innervating the cornea, project to the interpolar, oral and principal trigeminal nuclei and are somatotopically organized. Projections to the reticular formation and the contralateral trigeminal sensory complex were not found in this study. These results support the organization of the dorsal horn of the medulla proposed by Déjerine ('14) and show that this organization is most evident for the primary afferent projections to lamina II.
Adrenergic neurons from the superior cervical ganglion of the neonatal rat, when studied under certain culture conditions, develop cholinergic properties including hexamethonium-sensitive synaptic interactions, choline acetyltransferase activity and synaptic endings containing clear vesicles. Evidence from correlative biochemical, physiological and morphological studies on populations of neurons indicates that cholinergic function is acquired by the majority of neurons and not by subpopulation. The factors that influence the development of cholinergic function in culture include the presence of non-neuronal cells, the addition of human placental serum and chick embryo extract to the culture medium as well as the stage of development at which the neurons are placed in culture. Neurons from mature rats, maintained as explants in culture, develop low choline acetyltransferase activity and the synaptic endings containing dense-cored vesicles. In contrast, if dissociated, these adult neurons develop several cholinergic characteristics. Studies to determine which adrenergic properties are retained in neurons expressing cholinergic characteristics have shown an increase in the activities of tyrosine hydroxylase and dopamine beta-hydroxylase in both explanted and dissociated perinatal neurons. In addition, tyrosine hydroxylase has been localized immunocytochemically in neurons identified as cholinergic by electrophysiological methods.
1. Results obtained with the anterograde horseradish peroxidase (HRP) and autoradiographic techniques have revealed a dense and compact spinal and trigeminal projection to the dorsal portion of the nucleus submedius (Sm) in the medial thalamus of the cat. A homologous projection was observed in two cases in the monkey and in three cases in the rat with the anterograde HRP method. 2. The projection to Sm in topographically organized rostrocaudally, with trigeminal terminations located caudally and spinal terminations rostrally. The rostrocaudal extent of the trigeminal field in Sm (ca. 1 mm) is larger than that of the spinal field (ca. 0.8 mm). There is a considerable ipsilateral trigeminal projection, whereas there is a minimal uncrossed spinal projection to Sm. 3. Retrogradely labeled cells were analyzed in cases with small injections of HRP in medial thalamus in the cat. The results indicate that the projections to Sm identified in the anterograde experiments arise from lamina I cells of the spinal and medullary dorsal horm, probably exclusive of lamina V and other spinothalamic cells. The retrograde results corroborate the topographic observations made in the anterograde experiments. 4. These results suggest that Sm may be critically involved in specific nociception.
In vitro populations of neurons dissociated from the superior cervical ganglion of the rat embryo can acquire many of the properties of cholinergic neurons and yet retain some of the characteristics of adrenergic neurons. To determine whether one neuron can stably express properties of two transmitter systems, identified neurons were characterized by both immunocytochemical and electrophysiological methods. It was found that more than 90% of the neurons that formed functional cholinergic synapses had tyrosine hydroxylase within their cytoplasm. Furthermore, this mixed phenotypic expression persisted for more than 1 month. It is concluded that, under certain conditions in vitro, most neurons from the superior cervical ganglion have at least the potential for dual function.
The body representation in the second somatic sensory area of macaques has been studied by tracing with anatomical techniques the projections from defined parts of the body representation in the first somatic sensory area (SI) to their terminal regions within the lateral sulcus. The second somatic sensory area (SH), as identified in terms of cytoarchitecture and its connection with the thalamic ventrobasal complex, is the only region of the lateral sulcus to receive a projection from SI. The nearby retroinsular area and area 7b receive a projection from area 5. Within SII the face and head representations lie anteriorly, occupying the dorsalmost part of the insula and portions of the front-parietal operculum. The digits, hand, and arm are represented posterior to the face and may take up the mediolateral extent of the parietal operculum in the region immediately in front of the posterior pole of the insula. The trunk representation is lateral to the arm representation, i.e., deep within the superior circular sulcus and on the dorsal insula. The hindlimb appears behind the trunk also occupying the superior circular sulcus in addition to the deepest 2--3 mm of the upper bank of lateral sulcus immediately posterior to the insula. Areas 3b, 1, and 2 each project to SII, and their projections appear to converge within the representation of a given body part. Injections of anterogradely transported tracers in SI label vertically oriented columnar arrays of a terminal ramifications in SII, resembling those previously described for other cortico-cortical projections within the sensory-motor region. In experiments which combined anterograde and retrograde labeling, cells projecting from SII to SI formed columns exactly coinciding with the columns of anterogradely labeled axons terminating in SH. The cells of origin of cortico-cortical projections emanating from SII formed two distinct laminar populations, one in the supragranular layers and the second mainly in layer VI. There is evidence for fiber terminations within the layer VI mainly underlying the column formed by the terminal ramifications in layers I and through IV.
The second somatosensory area (SII) of awake, untrained cynomolgus monkeys was surveyed with recordings from nearly 1,000 single neurons. A detailed somatotopographic organization could be demonstrated in SII because the majority of these neurons had contralateral, moderate to well-defined receptive fields of < 10 cm2, and because neighboring neurons possessed receptive fields that were only slightly displaced from one another. Different body regions were represented in successive anterior to posterior strips that were oriented across the parietal operculum with an anterolateral to posteromedial slant. Neurons with trigeminal receptive fields were found in the anterior portion of SII; these neurons were the only ones in SII with predominantly bilateral receptive fields (r.f.'s.). Neurons with digit or hand r.f'.s form the largest component of the map, and were located posterior to those with face r.f.s. Most of these neurons had only contralateral activation. The hand and digit region was followed in turn by the arm, the upper and lower trunk, and the hindlimb regions. Although the overall SII orientation was along an anterior-posterior gradient, recordings at individual coronal planes often demonstrated isolated sequences of receptive fields that exhibited a medial-lateral progression. The principle example of this latter gradient was seen in the forelimb region where digits one through five were represented in an overlapping sequence across the parietal operculum. Except for portions of the digit representation, neighboring sequences of neurons in SII do not form a precise topologic map of the body that is comparable to the somatotopic maps observed in areas 3b and 1. The present findings contrast with previous physiological studies of SII in the primate. These discrepancies are discussed in relation to methodological differences and in terms of distinctions used to define the boundaries of SII.
The boundaries of the second somatic sensory cortex (SII) in primates are difficult to define physiologically because cutaneous stimulation activates several regions around SII that do not receive projections from the ventroposterior nucleus of the thalamus. These cortical regions, which include portions of area 7b, the retroinsular (Ri) and postauditory fields (PA), and the granular insula (Ig) are largely buried within the lateral sulcus and most lie posterior to the caudal end of the insula. The differences in somatic activity in these various cortical fields in the unanesthetized cynomolgus monkey became apparent only after the properties of many neighboring neurons could be compared. Receptive fields for area 7b and Ig neurons were generally large (< 10 cm2), with bilateral, moderately defined boundaries; some neurons in area 7b had receptive fields with labile borders as a function of wakefulness. In contrast, receptive fields for Ri neurons were generally (< 10 cm2 and contralateral, with stable, well-defined boundaries. Taken as an ensemble, the neurons in areas neighboring SII exhibited a very crude topography; but at the level of an individual neuron and its neighbor, there was never a pattern of gradual transition in peripheral receptive field locations between one unit and the next, like that seen in SII. In area 7b, this crude map was organized mediolaterally across the inferior parietal lobule and into the upper bank of the lateral sulcus, with the head represented medially and the lower trunk and hindlimb laterally. In Ri-PA, an anteroposterior organization was noted along the fundus of the lateral sulcus with the head represented anterior to the lower trunk and hindlimb. No organization was apparent in Ig. Additional sensitivity to visual stimuli was noted in the more medial aspects of area 7b that were located on the exposed inferior parietal lobule. Sensitivity to auditory stimuli was principally found in PA and occasionally in Ri. The results, especially from area 7b, are discussed with respect to previous notions about the organization of SII.
Somatic response properties were determined for over 1,300 neurons isolated within and near the lateral sulci of unanesthetized and unparalyzed cynomolgus monkeys. Somatic stimuli unequivocally activated the majority of units studied in SII (93%) and in cortical fields surrounding SII: area 7b (65%), the retroinsular field (74%), and the granular insula (76%). No activation other than somatic was seen for SII neurons, and noxious somatic stimulation was rarely required. The SII units almost always responded in a rapidly adapting manner to hair or skin stimulation, but not both; however, the submodality distribution seen in SII varied as a function of peripheral receptor locations. Two small zones within SII contained neurons that responded only if the animal actively interacted with the stimulus. In contrast, one-half of the sample of neurons from area 7b unequivocally responded only to somatic stimulation. Although many neurons in the lateral parts of area 7b were vigorously activated by innocuous tactile stimulation, others demonstrated little association with an identifiable somatic submodality, had sluggish responses, required complex, noxious, visual or other non-somatic stimuli for activation, and had labile response properties and receptive fields. Indeed, the responses of some area 7b neurons suggested a possible relationship with the animal's attention towards or anticipation of a noxious or a novel somatic stimulus. Neurons within the retroinsular cortex (Ri), which receives projections from the posterior nucleus (PO), primarily responded to light tactile stimulation of rapidly adapting skin receptors; less than 3% responded to moderate or high threshold mechanical stimulation. The sensitivity to tactile stimulation in Ri closely resembled the responses of SII neurons. Neurons in the granular insula (Ig) often responded to gentle hair deflection within receptive fields covering large areas of the body. Ig and area 7b were the principle loci within the lateral sulcus that contained neurons responding to noxious stimulation. Owing to the great similarity in the somatic response properties within these areas in the awake and unparalyzed animal, the designation of cortical areas could only be made after correlating the recording sites with connectional and cytoarchitectonic analyses in the same animal. Consequently, previous physiological studies may have attributed to SII some of the response characteristics of neurons in neighboring areas.
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The morphology of the lateral cervical nucleus (LCN) and the organization of the cervicothalamic projection neurons were studied in cats which had received thalamic injections of horseradish peroxidase (HRP). The boundaries of the LCN were defined following very large thalamic (HRP injections. Roughly 92-97% of LCN cells project contralaterally to thalamus; an additional 1.5% project ipsillaterally. Computer-assisted measurements of perikaryal areas demonstrated that there are two sizes of LCN cells, large (175-900 micrometer 2) and small (less than 175 micrometer 2); the small cells are localized in the medial third of the LCN. LCN cells which are not labeled after large thalamic HRP injections are predomininantly small, medially-located neurons. Small HRP injections into physiologically identified regions of ventroposterior thalamus demonstrated that cervicothalamic neurons are organized in a topography consistent with that observed physiologically in the LCN (Craig and Tapper, '78). Dorsolateral LCN cells are retrogradely labeled from nucleus ventroposterolateralis, pars lateralis (VPL1), ventromedial LCN cells are labeled from pars medialis (VPL m), and a few medial cells are labeled from nucleus ventroposteromedialis (VPM). A few cells in the medial portion of the LCN are also labeled from each part of ventroposterior thalamus. Some interspersion was observed even in the cases with the most well-restricted labeling. We conclude that the LCN maintains a basic somatotographic organization with an inherent variability, certain aspects of which are consistently demonstrable both physiologically and anatomically. Evidence was also obtained suggestive of a rostrocaudal inversion in the cervicothalamic projection. The cervicothalamic projection, the differentiation of the medial LCN subpopulation, and the possible redefinition of the LCN are discussed in light of these results.
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The efferent projections from nucleus caudalis of the spinal trigeminal complex in cats were studied with retrograde and anterograde axonal transport techniques combined with localization of recording sites in the thalamus and marginal zone of nucleus caudalis to innocuous skin cooling. Results showed brainstem projections from nucleus caudalis to rostral levels of the spinal trigeminal complex, to the ventral division of the principal trigeminal nucleus, the parabrachial nucleus, cranial motor nuclei 7 and 12, solitary complex, contralateral dorsal inferior olivary nucleus, portions of the lateral reticular formation, upper cervical spinal dorsal horn and, lateral cervical nucleus. Projections to the thalamus included; a dorsomedial region of VPM (bilaterally) and to the main part of VPM and PO contralaterally. Neuronal activity was recorded in the dorsomedial region of VPM to cooling the ipsilateral tongue. HRP injections in this thalamic region retrogradely labeled marginal neurons in nucleus caudalis. These results show that marginal neurons of nucleus caudalis provide a trigeminal equivalent of spinothalamic projections to the ventroposterior nucleus in cats.
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1. A morphological and physiological comparison was made between embryonically and postnatally derived superior cervical ganglion neurons (SCGN) grown in dissociated cell culture. It was found that while morphologically distinct, the physiological properties of the postnatal neurons were the same as their embryonic counterparts. 2. Intracellular injection of horseradish peroxidase (HPR) demonstrated that SCGN from any age of animal elaborated two basic types of processes, although the pattern of process ramification was unique for each neuron. The two types of proceses were 1) the large, smooth, rapidly tapering; and 2) the thin, nontapering variety, which often contained varicosities along its length. It is suggested that the former are dendritic in function, while the latter act as axons. 3. A difference was noted in somal size and the number of primary processes extended by the embryonic and postnatal neurons, with the latter more closely resembling the in vivo morphology. 4. Resting potentials and action-potential amplitudes of postnatal SCGN were comparable to those found previously for embryonic SCGN in vitro. 5. Iontophoretic application of putative neurotransmitter substances revealed the presence of acetylcholine receptors (AChR) on both embryonic and postnatal SCGN. Picrotoxin-sensitive depolarizing responses to iontophoresed gamma-aminobutyric acid (GABA) was seen on a few embryonic neurons, but not on the older cells. No responses were detected when norepinephrine (NE), glutamate, cAMP, substance P, or dopamine were applied to the SCGN of either age group. 6. Synatpic interaction between postnatal SCGN were found at an earlier in vitro age (12 days) than was the case for embryonic neurons (20 days). 7. Synaptic transmission was found to be chemical in nature. This was shown by 1) a dependence on external Ca2+ concentrations; 2) steplike fluctuations in synpatic potential amplitude, and 3) a variation in potential amplitude with changes in membrane potential. 8. It is concluded that the postnatal SCGN are able to survive in culture even when taken from animals up to 12.5 wk old. The elaboration of processes is in many ways strikingly similar to sympathetic neurons in the animal, and they are able to form functional synaptic interactions.
1. It was shown in the preceding paper that postnatally derived rat superior cervical ganglion neurons (SCGN) will grow in dissociated cell culture and form functional synaptic connections with each other. In this report, synaptic transmission by the postnatal SCGN is detailed. 2. Synaptic interactions between SCGN were blocked by the nicotinic cholinergic antagonist hexamathonium (C-6), indicating that acetylcholine was the transmitter substance used by these neurons. This was found to be the case even for neurons taken from 12.5-wk-old animals. 3. In a few cases, the beta-adrenergic blocking agent, propranolol, was found to block synaptic potentials, suggesting that a catecholamine might be involved in the transmission process. The possible mechanisms of this involvement are discussed. 4. SCGN taken from up to 10-wk-old rats were able to form functional synaptic contacts with cocultured skeletal muscle cells. These interactions were sensitive to low external Ca2+ and to 1--2 microM d-tubocurarine (d-TC). 5. It is concluded that even adult SCGN retain a certain amount of neurotransmitter "plasticity" when grown under appropriate culture conditions. From the data on the neuron-neuron and SCGN-skeletal muscle interactions, it is suggested that a matching of presynaptic transmitter with postsynaptic receptor is a sufficient condition for the formation of functional nerve-target interactions.
The efferent projections from the solitary complex to the lower brain stem and spinal cord were studied in the cat with the autoradiographic anterograde axonal transport and retrograde horseradish peroxidase (HRP) techniques. A revised cytoarchitectonic description of the caudal two-thirds of the complex is presented in which the complex was subdivided into six nuclei: lateral, ventrolateral, intermediate, medial, parvocellular, and commissural solitary tract nuclei. Following injections of 3H amino acids into electrophysiologically defined regions of the complex in which cardiac or respiratory units were recorded, labeled fibers could be traced to a number of sites in the caudal brain stem including the medial and lateral parabrachial nuclei, Kölliker-Fuse nucleus and the area ventral to this nucleus, lateral periaqueductal gray matter, ambiguus complex, which consists of the retrofacial, ambiguus and retroambiguus nuclei, ventrolateral reticular nucleus (in an area equivalent to the A1 cell group of Dahlström and Fuxe, '64), medial accessory olive, paramedian reticular formation, and lateral cuneate nucleus. Descending solitario-spinal projections have been traced bilaterally, but predominantly to the contralateral side, to the region of the phrenic motor neurons in the C4-C6 ventral horn, to the thoracic ventral horn, and intermediolateral cell column. Confirmatory evidence of some of these projections was obtained from a series of HRP experiments. Mainly small neurons of the parvocellular, medial and commissural solitary tract nuclei project to the region of the parabrachial and Kölliker-Fuse nuclei. The lateral solitary nucleus projects almost exclusively to the ipsilateral medial accessory olive. It was not possible to interpret conclusively the labeling seen in the medium and large neurons of the ventrolateral solitary nucleus after HRP injections made in the region of the ambiguus-retroambiguus complex due to the problem of fibers of passage. Following injections of HRP into the cervical, thoracic, lumbar, or sacral spinal cord, retrograde cell labeling was seen in the solitary complex. Cells in the intermediate and commissural nuclei were labeled after all four types of experiments. In the ventrolateral nucleus, medium sized neurons were predominantly labeled after the cervical spinal cord experiments, while large sized neurons were labeled mainly after the thoracic spinal cord injections. The potential physiological significance of these connections is discussed in terms of central control of cardiovascular and respiratory functions.
Cultures of dissociated rat superior cervical ganglion neurons (SCGN) were treated with the sympatholytic agent, guanethidine. When treated within the first couple of weeks in vitro, the neurons were rapidly destroyed. The cells grew less susceptible to the toxic effects of guanethidine with age in vitro. Moreover, the apparent affinity, Km, of the transport molecule for norepinephrine (NE) and guanethidine remained essentially unchanged between 2 and 7 wk in culture, as did the maximum velocity of transport (Vmax). This is at a time when previous studies have shown these neurons to be using acetylcholine (ACh) as their neurotransmitter. Cultures which were grown without supporting cells and from which cholinergic synaptic interactions were recorded physiologically were processed for autoradiography after incubation with [3H]NE. All cell bodies and processes seen had silver grains accumulated over them. These experiments show that sympathetic neurons in vitro maintain their amine uptake system relatively unchanged, even though they use ACh as their transmitter. The implications of these findings are discussed.