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E T Cunningham

Publications and source records attributed to E T Cunningham.

85 records · Page 5Linked to original sources
PubMed1991

Enkephalin immunoreactivity and messenger RNA in a discrete projection from the nucleus of the solitary tract to the nucleus ambiguous in the rat.

Previous work described in the rat a circumscribed, partly somatostatinergic, interneuronal projection from the esophageal afferent part of the nucleus of the solitary tract (NTSc) to esophageal motor neurons in the compact formation of the nucleus ambiguous (NAcf: Cunningham and Sawchenko, J Neurosci 9:1668, 1989). In the present study, axonal transport, immunohistochemical and in situ hybridization histochemical techniques were used to determine whether enkephalin (ENK), a peptide known to be expressed in a number of somatostatin-containing medullary cell groups, is also expressed in the projection from the NTSc to the NAcf. The results may be summarized as follows: 1) cells immunoreactive (IR) for prepro-enkephalin (ppENK)-derived peptides were found in the NTSc in colchicine-pretreated animals; in untreated animals, a dense ENK-IR terminal field was observed in the NAcf: sections stained with antisera against dynorphin-related peptides showed sparse staining in both regions; 2) signal indicating the presence of ppENK messenger RNA (mRNA) was found over the NTSc, including over a majority of cells identified using a retrograde tracing technique as projecting to the region of the NAcf; the signal for ppENK mRNA signal was greater than that for prepro-somatostatin (ppSS) in the NTSc; 3) a combined anterograde tracing-immunohistochemical technique demonstrated a strong correspondence between the distribution of inputs from the NTS to the NAcf, and the distribution of endogenous ENK-IR varicosities; in addition, leucine (L)-ENK-IR was found in an appreciable number of varicosities in the NAcf that had been anterogradely labeled from the NTSc; 4) unilateral electrolytic lesions of the rostromedial NTS, which included the central subnucleus, virtually eliminated ENK-IR in the ipsilateral NAcf, while staining on the contralateral side was unaffected. Taken together, these studies provide evidence that ppENK- and ppSS-derived peptides are expressed in the pathway from the NTSc to the NAcf, a pathway thought to play a role in the reflex control of esophageal peristalsis.

Animals↗
PubMed1991

Reflex control of magnocellular vasopressin and oxytocin secretion.

Reflex control of magnocellular vasopressin and oxytocin secretion has captured the curiosity and investigative imagination of neuroendocrinologists for nearly 50 years. While it may seem obvious that brisk elevations in circulating levels of vasopressin in response to hemorrhage, or of oxytocin in response to suckling, must of necessity arise from magnocellular neurosecretory neurons in the hypothalamus, the central pathways mediating these reflexes have, until quite recently, remained elusive. In this brief review, ongoing attempts to delineate these pathways are summarized. Evidence for plasticity and local modulation of magnocellular reflexes in response to prolonged stimulation, such as chronic dehydration and lactation, is also presented.

Animals↗
PubMed1991

Development of intrastriatal striatal grafts and their afferent innervation from the host.

The morphological maturation of cell suspension grafts of fetal striatal tissue (obtained from 14-15-day-old rat fetuses) was followed from two days to eight weeks after implantation into intact and ibotenic acid-lesioned striata of adult rats. The development of host afferent innervation of the grafts from the substantia nigra (tyrosine hydroxylase immunoreactive), mesencephalic raphe (serotonin immunoreactive), and the frontal cortex (anterogradely labelled with Phaseolus vulgaris leucoagglutinin) were revealed by immunohistochemistry. During the first weeks post-grafting, the striatal implants consisted of a mixture of mature- and immature-looking cell clusters. Grafts implanted into ibotenic acid-lesioned striatum grew rapidly (about five-fold) in volume over the first week. The areas of immature (probably proliferating) cells gradually disappeared, and by six to eight weeks the grafts had a fully mature appearance with patches of neurons which stained densely for DARPP-32 (i.e. were striatum-like) embedded within areas of essentially DARPP-32-negative (i.e. non-striatum-like) tissue. Peripheral clusters of grafted cells gradually intermingled with nearby areas of the surrounding lesioned host, and already by two to four days after implantation, coarse and densely immunoreactive host fibres from the substantia nigra, mesencephalic raphe and frontal cortex were present within the grafts. By four to five days the first DARPP-32-immunoreactive neurons appeared in patches within the mature portions of the grafts, and one to two days later the tyrosine hydroxylase-positive fibres began to sprout thin axons selectively within the DARPP-32-positive patches. Similarly, the serotonergic and cortical fibres in the grafts increased in number over the next two weeks, but they showed no preference for the DARPP-32-positive regions. Rich terminal networks were established by two to three weeks post-grafting, and by six to eight weeks the nigral, raphe and cortical afferents had reached terminal densities similar to those seen previously in long-term surviving grafts. Grafts implanted into dopamine-denervated hosts showed a normal morphological maturation of both DARPP-32-positive and -negative areas, although no tyrosine hydroxylase-positive innervation appeared within the grafts. Grafts implanted into non-lesioned striata did not grow beyond their initial size. The implanted cells showed less intermingling with the surrounding host striatum, thus resulting in sharply delineated graft-host borders. DARPP-32-positive patches developed, but they were smaller in size and generally present only in the most peripheral graft portions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Localization of interleukin-1 receptor messenger RNA in murine hippocampus.

The cytokine interleukin-1 (IL-1) has numerous actions in brain, including pronounced neuroendocrine effects. Recent radioligand binding studies have identified high-affinity binding sites for 125I-recombinant human IL-1 alpha in the hippocampus with characteristics similar to those of IL-1 receptors in immune cells. The present study employed in situ hybridization histochemistry with 35S-labeled anti-sense cRNA probes derived from a full-length murine T-cell IL-1 receptor cDNA to identify cells producing IL-1 receptor mRNA in the murine hippocampus. An intense signal was observed over granule cells in the dentate gyrus. A weak to moderate signal was observed over the pyramidal cell layer of the hilus and CA3 region. Other aspects of the hippocampal formation, including the CA2 and CA1 regions, the subiculum, and the entorhinal area, displayed no signal above background. This distribution of IL-1 receptor mRNA was similar to that of 125I-IL-1 alpha binding sites and supports the growing body of evidence implicating IL-1 as a neurotransmitter/neuromodulator in brain.

Animals↗
PubMed1991

Fourth nerve paresis and ipsilateral relative afferent pupillary defect without visual sensory disturbance. A sign of contralateral dorsal midbrain disease.

We describe a patient with a left trochlear nerve paresis and a left relative afferent pupillary defect despite normal visual acuity, color vision, visual fields, and fundus examination. Magnetic resonance imaging revealed a lesion in the right dorsal midbrain extending from the brachium of the superior colliculus to the inferior colliculus. The anatomy and physiology of the pupillary light reflex are reviewed, as are possible mechanisms for the laterality of afferent pupillary defects with midbrain lesions. The presence of a trochlear nerve paresis with an ipsilateral relative afferent pupillary defect and an otherwise normal ophthalmic exam indicates a lesion in the contralateral dorsocaudal midbrain.

Adult↗
PubMed1990

Organization of adrenergic inputs to the paraventricular and supraoptic nuclei of the hypothalamus in the rat.

Anterograde transport, retrograde transport, and immunohistochemical techniques were used to characterize the organization of neural inputs to the paraventricular (PVH) and supraoptic (SO) nuclei from the C1, C2, and C3 adrenergic cell groups in the rostral medulla. The results are as follows: 1) Phenylethanolamine-N-methyltransferase-immunoreactive (PNMT-IR) fibers and terminals were distributed to all parts of the parvicellular division of the PVH; the dorsal and dorsal medial subdivisions received the most prominent inputs, the lateral and ventral medial parts the least. Sparse terminal fields were found consistently in the magnocellular division of the PVH and in the SO. 2) A combined retrograde transport-immunohistochemical method was used to estimate the number and proportion of cells in the regions of the C1, C2, and C3 cell groups that contribute to the PNMT-IR innervation of the PVH. On average, 232 +/- 37 retrogradely labeled cells in the C1 cell group, 73 +/- 32 in the C2 cell group, and 96 +/- 26 in the C3 group stained positively for PNMT-IR. These values comprised 70%, 84%, and 89%, respectively, of all retrogradely labeled neurons in these regions. 3) Fibers and terminals arising from the regions of each of the three adrenergic cell groups were labeled by local injections of the anterogradely transported plant lectin PHA-L. Each component projection was found to distribute in a very similar fashion and to mimic the overall distribution of PNMT-IR; differential projection patterns within the PVH or SO were not seen consistently following deposits in any of the individual adrenergic cell groups or at different rostrocaudal levels of any individual cell group. 4) A dual anterograde tracing (PHA-L)-immunohistochemical (PNMT) labeling method revealed an appreciable number of varicosities arising from the regions of C1, C2, and C3 cell groups to contain PNMT-IR. These results suggest that adrenergic inputs to the PVH and SO, while arising from distinct medullary cell groups and presumably relaying different types of sensory information, are in a position to influence similar groups of parvicellular neurosecretory and/or autonomic-related projection neurons.

Adrenergic Fibers↗
PubMed1990

Central neural control of esophageal motility: a review.

We review recent studies on the central neural control of esophageal motility, emphasizing the anatomy and chemical coding of esophageal pathways in the spinal cord and medulla. Sympathetic innervation of the proximal esophagus is derived primarily from cervical and upper thoracic paravertebral ganglia, whereas that of the lower esophageal sphincter and proximal stomach is derived from the celiac ganglion. In addition to noradrenaline, many sympathetic fibers in the esophagus contain neuropeptide Y (NPY), and both noradrenaline and NPY appear to decrease blood flow and motility. Preganglionic neurons innervating the cervical and upper thoracic ganglia are located at lower cervical and upper thoracic spinal levels. The preganglionic innervation of the celiac ganglion arises from lower thoracic spinal levels. Both acetylcholine (ACh) and enkephalin (ENK) have been localized in sympathetic preganglionic neurons, and it has been suggested that ENK acts to pre-synaptically inhibit ganglionic transmission. Spinal afferents from the esophagus are few, but have been described in lower cervical and thoracic dorsal root ganglia. A significant percentage contain calcitonin gene-related peptide (CGRP) and substance P (SP). The central distribution of spinal afferents, as well as their subsequent processing within the spinal cord, have not been addressed. Medullary afferents arise from the nodose ganglion and terminate peripherally both in myenteric ganglia, where they have been postulated to act as tension receptors, and, to a lesser extent, in more superficial layers. Centrally, these afferents appear to end in a discrete part of the nucleus of the solitary tract (NTS) termed the central subnucleus. The transmitter specificity of the majority of these afferents remains unknown. The central subnucleus, in turn, sends a dense and topographically discrete projection to esophageal motor neurons in the rostral portion of the nucleus ambiguous (NA). Both somatostatin-(SS) and ENK-related peptides have been localized in this pathway. Finally, motor neurons from the rostral NA innervate striated portions of the esophagus. In addition to ACh, these esophageal motor neurons contain CGRP, galanin (GAL), N-acetylaspartylglutamate (NAAG), and brain natriuretic peptide (BNP). The physiological effect of these peptides on esophageal motility remains unclear. Medullary control of smooth muscle portions of the esophagus have not been thoroughly investigated.

Esophagus↗
PubMed1989

A circumscribed projection from the nucleus of the solitary tract to the nucleus ambiguus in the rat: anatomical evidence for somatostatin-28-immunoreactive interneurons subserving reflex control of esophageal motility.

Axonal transport and immunohistochemical methods were used to investigate the anatomical and biochemical organization of projections from the nucleus of the solitary tract (NTS) to the rostral, esophageal, part of the nucleus ambiguus (NA) in the rat. Discrete iontophoretic deposits of a retrogradely transported tracer, fluorogold, placed in the rostral NA labeled a column of cells within the NTS, termed the central part of the NTS (after Ross et al., 1985), situated just medial to the solitary tract and extending from about 300 to 1000 microns rostral to the obex. Iontophoretic deposits of the anterogradely transported tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), placed in the central part of the NTS gave rise to dense and topographically restricted projections to the rostral NA. More caudal and ventral aspects of the NA did not receive prominent inputs from the central part of the NTS, and deposits that spared the central part of the NTS gave rise to only sparse projections to the rostral NA. Antisera against somatostatin-28 (SS-28) stained cell bodies within the central part of the NTS. In addition, a double-labeling procedure, capable of colocalizing anterogradely transported PHA-L and endogenous peptides to individual fibers and/or terminals, demonstrated an appreciable number of SS-28-immunoreactive terminals within the rostral NA that arose from the NTS. Correspondingly, unilateral lesions that involved the central part of the NTS resulted in a marked depletion of SS-28 immunoreactivity in the ipsilateral rostral NA. These data provide evidence for a discrete, partly somatostatinergic, projection from the central part of the NTS to the rostral NA. Anatomical and physiological studies implicating the central part of the NTS and the rostral NA in esophageal function suggest this pathway to be involved in the reflex control of esophageal motility.

Animals↗
PubMed1988

Inhibin beta in central neural pathways involved in the control of oxytocin secretion.

Inhibin (I) a gonadal hormone glycoprotein which suppresses follicle-stimulating hormone (FSH) secretion from the anterior pituitary, is a heterodimer consisting of an alpha subunit and one of two distinct beta subunits. S1 nuclease analysis has revealed that RNAs encoding all three subunits (alpha, beta A and beta B) are expressed in rat brain. We report here on the localization, and a potential function, of inhibin beta in the rat brain. A cell group centred in the nucleus of the solitary tract (NTS), a major recipient of visceral sensory information, was stained immunohistochemically with antisera against synthetic fragments of I beta, but not I alpha. The distribution of I beta-stained fibres is consistent with known NTS projections, and includes a prominent projection to oxytocinergic aspects of the magnocellular neurosecretory system.

Animals↗
PubMed1988

Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus.

The distribution of neural inputs to the paraventricular (PVH) and supraoptic (SO) nuclei from the regions of the A1, the A2, and the A6 (locus coeruleus) noradrenergic cell groups was investigated by using a plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L), as an anterogradely transported tracer. An immunofluorescence double-labeling procedure was used to determine the extent to which individual anterogradely labeled fibers and terminals in the PVH and the SO also displayed immunoreactive dopamine-beta-hydroxylase (DBH), a marker for catecholaminergic neurons. The results may be summarized as follows: (1) Projections from the A1 region were found primarily, and in some experiments almost exclusively, in those parts of the magnocellular division of the PVH and the SO known to contain vasopressinergic neurons. (2) Projections from the A2 region were distributed primarily throughout the parvicellular division of the PVH and were most dense in the dorsal medial part, a region known to contain a prominent population of corticotropin-releasing factor (CRF)-immunoreactive neurons. In addition, a less-dense projection to the magnocellular division of the PVH and to the SO was consistently found. (3) Fibers originating from the locus coeruleus were distributed almost exclusively to the parvicellular division of the PVH, with the most prominent input localized to the periventricular zone, a part of the PVH known to contain dopamine-, somatostatin-, and thyrotropin-releasing-hormone-containing neurons. We found no evidence for a projection from A6 to the SO. (4) The majority of fibers originating from the A1, the A2 or the A6 regions contained DBH immunoreactivity, although an appreciable number did not. These results suggest that each of the three brainstem noradrenergic cell groups that contribute to the innervation of the PVH and/or the SO is in a position to modulate the activity of anatomically and chemically distinct groups of neurosecretory neurons.

Afferent Pathways↗
PubMed1986

Laminar and synaptic organization of the projection from the thalamic nucleus centralis to primary visual cortex in the cat.

The projection from the nucleus centralis (an intralaminar thalamic nucleus) to the primary visual cortex was examined with anterograde and retrograde tracing techniques. After large injections of horseradish peroxidase into areas 17 and 18 almost one-half of the neurons in the nucleus centralis were retrogradely labeled. An injection of 3H-proline into the nucleus centralis led to sparse anterograde labeling in layers 5 and 6 of areas 17 and 18. Large injections of peroxidase-conjugated wheat germ agglutinin (WGA) into the nucleus centralis led to similar anterograde labeling of layers 5 and 6 and, in addition, to a band in layer 1. No retrogradely labeled cells were seen in areas 17 or 18. The WGA-labeled terminals in area 17 were examined in the electron microscope: they formed type 1 (asymmetric) synapses on dendritic spines. These observations suggest that the afferents from the nucleus centralis primarily contact pyramidal cells that project to subcortical targets. The findings are consistent with physiological studies suggesting that the nucleus centralis is involved in the modulation of cortical outflow with varying levels of arousal.

Afferent Pathways↗
PubMedDate not supplied

The Francis I. Proctor Foundation: the first fifty years.

September 15, 1997 marked the golden anniversary of the Francis I. Proctor Foundation, which was established in affiliation with the University of California in San Francisco. Over 50 years, 182 fellows from 27 countries have been trained in programs focusing on the study of infectious and inflammatory eye disease, and the prevention of blindness worldwide. Many of the people and events that have contributed to the success of the Proctor Foundation are presented in this brief essay.

Anniversaries and Special Events↗