Brainstem distribution of neurons with efferent projections in the cervical vagus of the dog

The distribution within the brainstem of cell bodies and efferent fibers projecting in the cervical vagus was studied with retrograde transport of horseradish peroxidase (HRP). Five to eight days after multiple microinjections of HRP into either the cervical vagosympathetic trunk or the nodose ganglion the brainstems and nodose ganglia were perfused and processed by the tetramethyl benzidine method. HRP-positive neurons were found in three brainstem regions: a dorsal cell column comprising the dorsal motor nucleus of the vagus (dmnX), a ventrolateral group in the region of nucleus ambiguus (nA), and scattered cells along a line between these columns. The density of labeled neurons was greatest within dmnX. Axons from cells of the ventrolateral column projected dorsomedially; just ventral to dmnX they turned laterally to exit the medulla in multiple rootlets. Within nA labelled neurons were distributed according to size, with larger cells more medial and smaller ones more lateral. Caudal to nA in nucleus retroambigualis and nucleus dorsalis medialis cell bodies appeared segregated into clusters.     

Extranuclear axon collaterals of paraventricular neurons in the rat hypothalamus: Intracellular staining, immunocytochemistry and electrophysiology

Recent studies have suggested that some paraventricular nucleus (PVN) neurons projected to more than one target and, thereby, perhaps coordinate some aspects of seemingly diverse functions. We have systematically investigated the existence, location, hormonal contents and functional integrity of some axon collaterals arising from PVN neurons. This was done using intracellular injections of the fluorescent dye, Lucifer Yellow, extracellular ejections of horseradish peroxidase (HRP), immunocytochemistry with antisera directed against vasopressin (VP) and oxytocin (OX) and electrophysiological analysis of synaptic activation of perifornical neurons in response to electrical stimulation of the PVN in hypothalamic slices. Each of the three morphological techniques revealed clear axon collaterals, arising in the lateral hypothalamus and generally ventrolateral to the PVN. Most branching axons appeared to have a small number of branch points, and many collaterals appeared to terminate near their parent axon. Electrical stimulation of the PVN was found to activate synaptically perifornical neurons located in the areas where the other methods revealed collaterals. Stimulation outside of the nucleus was ineffective unless current intensities were increased 10-30-fold over those applied to the PVN. We conclude that many PVN neurons, at least some of these containing OX and other VP, give rise to axons that branch in the perifornical and more ventral lateral hypothalamus, and that some of their collaterals probably terminate on neurons close to the PVN.     

Autonomic control and bariatric procedures

The sudden improvement of metabolic profile and the remission of type 2 diabetes after bariatric surgery, well before weight loss, raise important new questions regarding glycemic control. Currently, various types of bariatric procedures target type 2 diabetes in obese and non-obese patients. Nevertheless, the origin of the dramatic metabolic improvements, including glucose homeostasis, is poorly understood, and the role of the gastrointestinal (GI) tract remains relatively speculative, as well as why these procedures are variably effective. One neglected explanation is that such interventions disrupt neural networks mediating GI–brain communication and could alter the autonomic output to the visceral organs, including the liver. Incretins, e.g., glucagon-like peptide 1 (GLP-1), have major influence on the central nervous system. Moreover, the level of GLP-1 is observed to significantly increase after bariatric surgery and could be a key factor in the weight-independent, anti-diabetic effect. Therefore, this review will evaluate the effect of GLP-1 on the central nervous system, with emphasis on the cellular effects of GLP-1, and will provide an overview of the autonomic control of the liver.     

Cells of origin of corticospinal projections to phrenic and thoracic respiratory motoneurones in the cat as shown by retrograde transport of HRP

A combined electrophysiological and histological approach was employed to identify neurones within the motor cortex which project to the vicinity of spinal respiratory motoneurones, and which may be involved in the alteration of the pattern of breathing under certain conditions. Recording of respiratory phased activity from phrenic, or from thoracic motoneurones within either the upper (T3-4) or lower (T8-9) segments, was followed by the iontophoretic injection of HRP at these recording sites. After injections within the cervical or thoracic ventral horn, 219 cells were retrogradely labelled in 14 experiments. The majority of these cells (88%) were labelled contralateral to the injection site. Following the injection of HRP into the phrenic nucleus, labelling was observed at two major sites within the anterior sigmoid gyrus (ASG), one along the anterolateral edge of the cruciate sulcus, and the other along the ventrolateral border of the ASG. In contrast, cells labelled after injections into the thoracic ventral grey matter were located more medially within the ASG and the posterior sigmoid gyrus (PSG). The populations of cells labelled following phrenic and thoracic injections overlapped, primarily at the lateral edge of the cruciate sulcus. The somas of labelled cells were pyramidal, round or oval. The mean diameters of cortical cells labelled after injections into the lower or upper thoracic segments were 30.5 +/- 6.2 and 31.5 +/- 5.6 respectively, which were not significantly different in size. However, they were significantly larger than the mean diameter of the cells labelled from injections into the phrenic nucleus (22.7 +/- 4.2 micron).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fos induction in selective hypothalamic neuroendocrine and medullary nuclei by intravenous injection of urocortin and corticotropin-releasing factor in rats

CRF and urocortin, administrated systemically, exert peripheral biological actions which may be mediated by brain pathways. We identified brain neuronal activation induced by intravenous (i.v.) injection of CRF and urocortin in conscious rats by monitoring Fos expression 60 min later. Both peptides (850 pmol/kg, i.v.) increased the number of Fos immunoreactive cells in the paraventricular nucleus of the hypothalamus, supraoptic nucleus, central amygdala, nucleus tractus solitarius and area postrema compared with vehicle injection. Urocortin induced a 4-fold increase in the number of Fos-positive cells in the supraoptic nucleus and a 3.4-fold increase in the lateral magnocellular part of the paraventricular nucleus compared with CRF. Urocortin also elicited Fos expression in the accessory hypothalamic neurosecretory nuclei, ependyma lining the ventricles and choroid plexus which was not observed after CRF. The intensity and pattern of the Fos response were dose-related (85, 255 and 850 pmol/kg, i.v.) and urocortin was more potent than CRF. Neither CRF nor urocortin induced Fos expression in the lateral septal nucleus, Edinger-Westphal nucleus, dorsal raphe nucleus, locus coeruleus, or hypoglossal nucleus. These results show that urocortin, and less potently CRF, injected into the circulation at picomolar doses activate selective brain nuclei involved in the modulation of autonomic/endocrine function; in addition, urocortin induces a distinct activation of hypothalamic neuroendocrine neurons.     

Vagal neurons and pathways to the rat's lower viscera: An electrophysiological study

The vagal pathways to the rat's pancreas are anatomically difficult to describe. A stimulation/recording technique has been used on various segments of the vagus to trace vagal pathways to the lower viscera, and a microelectrode recording technique to locate vagal neurons of origin in the brain stem's dorsal motor nucleus (DMX). The two main pathways (right cervical vagus to dorsal celiac branch and left cervical vagus to ventral celiac branch) are supplemented by two accessory ones where each cervical vagus gives some fibers to its contralateral homologue at the diaphragmatic level. These pathways consist almost exclusively of C-fibers. Neurons of origin of the dorsal vagal trunk fibers have been identified by the collision test and occupy the caudal half of the DMX; those of the dorsal celiac branch fibers originate from the medial part of that area.     

Fos expression in the brain induced by peripheral injection of CCK or leptin plus CCK in fasted lean mice

We previously reported a synergistic interaction between leptin and cholecystokinin (CCK) to reduce food intake through CCK-A receptors in lean mice fasted for 24 h. To identify the activated neuronal pathways, we investigated changes in Fos expression in brain nuclei 2 h after single or combined intraperitoneal (i.p.) injections of leptin (120 μg/kg) and sulfated CCK-8 (3.5 μg/kg) in male lean mice (C57BL/6) fasted for 24 h using immunohistochemistry for Fos, the protein product of the early gene, c-fos. Leptin did not increase Fos expression in the brain compared with vehicle-treated mice. CCK increased the numbers of Fos-positive neurons in the nucleus of the solitary tract (NTS)/area postrema (AP), central nucleus of the amygdala (CeA) and, to a smaller extent, in the paraventricular nucleus of the hypothalamus (PVN) (5.2-, 2.3- and 0.3-fold respectively). Injections of leptin–CCK further enhanced Fos expression by 40% in the PVN compared with that induced by CCK alone, but not in the other nuclei. Devazepide (a CCK-A receptor antagonist, 1 mg/kg, i.p.) prevented the increase in Fos expression induced by leptin–CCK in the PVN and by CCK alone in the PVN, CeA and NTS/AP. These results indicate that in fasted mice, i.p. injection of CCK increases Fos expression in specific brain nuclei through CCK-A receptors while leptin alone had no effect. Leptin in conjunction with CCK selectively enhanced Fos expression in the PVN. The PVN may be an important site mediating the synergistic effect of leptin–CCK to regulate food intake.     

Spontaneous and osmotically-stimulated activity in slices of rat hypothalamus

HATTON, G. I., W. E. ARMSTRONG AND W. A. GREGORY. Spontaneous and osmotically stimulated activity in slicesof rat hypothalamus. BRAIN RES. BULL. 3(5) 497–508, 1978.—Single unit activity was recorded from 400–500 μm thick slices of rat hypothalamus, using either NaCl- or horseradish peroxidase-filled glass micropipettes. Spontaneous activity was present in the following hypothalamic loci: anterior hypothalamic-preoptic area, nucleus circularis, nucleus of the diagonal band of Broca, paraventricular accessory nucleus, paraventricular nucleus (all portions), periventricular regions of the anterior hypothalamus, and the suprachiasmatic nucleus. The supraoptic nucleus was the only major cell group studied to exhibit no spontaneous activity. Cells of the paraventricular and circularis nuclei were spontaneously active, displayed firing rates and patterns of activity similar to those recorded in vivo for magnocellular elements of the hypothalamus, and in some cases responded to increases in the osmolality of the bathing medium with altered firing rates and/or patterns of activity. Many cells in these preparations were characterized by phasic, bursting patterns of activity. Slow, irregular and regular, continuous activity was also frequently observed, as is typical in vivo. Median firing rates were in the range of 4–6 spikes/sec, somewhat faster than the rates usually reported for anesthetized in vivo preparations. These rates are more similar to those observed in unanesthetized monkeys or rats with diencephalic islands. Extracellular HRP marking provided a high degree of localization for many of the recorded cells. These results indicate that the hypothalamic slice preparation is useful for studies in which it is desirable to eliminate extrahypothalamic connections and in which it is necessary to exercise a fine degree of control over the extracellular environment of the cells.     

大鼠下丘脑室旁核小胶质细胞对次声的反应

目的探讨次声作用后大鼠下丘脑室旁核小胶质细胞与星形胶质细胞的变化及其相互关系。方法将SD大鼠反复暴露于声压级16Hz130dB的次声环境中。用抗大鼠Ⅲ型补体受体标志物（0X42）和抗胶质细胞原纤维酸性蛋白（GFAP）的免疫组化方法，观察次声作用后即刻，7d，14d大鼠下丘脑室旁核小胶质细胞与星形胶质细胞的变化及其相互关系。结果正常大鼠下丘脑室旁核的小胶质细胞和星形胶质细胞的数量较少，一般为静息性形态，胞体小，突起细长，染色浅淡。次声作用后大鼠下丘脑小胶质细胞被激活，胞体变大，突起短粗，染色深，7d以后逐渐减弱；次声作用后第7d起星形胶质细胞变多，胞体变大，突起变粗，染色深，第14d达到高潮；小胶质细胞和星形胶质细胞之间的关系密切。结论次声作用后小胶质细胞比星形胶质细胞早被激活；两者的关系密切。     

Neuronal control of the ventromedial nucleus from the periventricular nucleus in the hypothalamic slice of the rat

A neuronal pathway between periventricular nucleus and ventromedial hypothalamus (VMH) was investigated by both anatomical and electrophysiological methods. Horseradish peroxidase (HRP)-labelled clusters were observed in the periventricular nucleus after application of HRP into the VMH. Periventricular nucleus stimulation produced mainly excitation of VMH neurones with a latency of 3 msec. These results suggest that periventricular nucleus sends information in the cerebro-spinal fluid to the VMH.     

Direct vagal input to neurons in the area postrema which project to the parabrachial nucleus: An electron microscopic-HRP study in the cat

This study in cat examines the synaptic relationship of vagal afferents to parabrachial projecting neurons in the area postrema (AP) using anterograde and retrograde transport of horseradish peroxidase (HRP). Wheat germ agglutinin-HRP injected into the parabrachial nucleus (PBN) produced retrograde neuronal labeling in the AP and in the nucleus of the tractus solitarius bilaterally, but with an ipsilateral predominance. Labeled neurons were confined mainly to the caudal 2/3's of the AP. Following injection of WGA-HRP into the PBN and HRP into the nodose ganglion in the same animal, examination of sections of the AP with the electron microscope revealed anterogradely labeled axon terminals in apposition to retrogradely labeled somata and dendrites. In some instances, labeled terminals were observed to form synaptic contacts with retrogradely labeled neurons. We conclude that in the cat a vagal input to neurons in the AP is monosynaptically relayed to the PBN.     

Reciprocal circuits involved in nitroglycerin-induced neuronal activation of autonomic regions and pain pathways: a double immunolabeling and tract-tracing study

This study uses tract-tracing protocols to determine the circuitry of specific nuclei involved in nitroglycerin-induced activation. Combined retrograde and anterograde tracers were injected into nuclei which consistently demonstrate robust Fos expression following our systemic nitroglycerin injection paradigm. The nuclei, which conform to these criteria, that we have evaluated in this study are the locus coeruleus, parabrachial nucleus and paraventricular nucleus of the hypothalamus. Dual Fos/tracer immunocytochemistry in treated animals documented the existence of a subset of autonomic nuclei which are activated by nitroglycerin injection and have reciprocal connections. From the nature of this rich interconnection we suggest that nitroglycerin activates autonomic responses involved in cardiovascular pressor mechanisms. Nuclei which show strong Fos labeling following nitroglycerin administration, but not traced in this study, include the nucleus trigeminalis caudalis and the ventrolateral column of the periaqueductal gray, both of which mediate nociceptive modalities. These data confirm and expand on our previous findings and demonstrate that nitroglycerin activates a complex set of structures that are functionally and structurally interconnected to articulate an integrated response.     

The pretectal complex of the cat: cells of origin of projections to the pulvinar nucleus

The pretectal projection to the pulvinar nucleus in the cat was examined ussing the retrograde transport of wheat germ agglutinin—horseradish peroxidase. These data show that both visual and non-visual areas of the pretectal complex contribute to the projection. Specifically, large numbers of labeled neurons are located within the pretectal olivary nucleus with a substantial number of labeled neurons observed within the nucleus of the optic tract. Labeled neurons are also located within the medial, anterior and posterior nuclei, but not to the degree observed in the other pretectal nuclei. Morphometric analysis of labeled and Nissl-stained neurons indicate that the pretectopulvinar pathway is not correlated to any single cell size.