Transneuronal labeling of CNS neuropeptide and monoamine neurons after pseudorabies virus injections into the stellate ganglion

Jansen, A.S.P.; Wessendorf, Martin W.; Loewy, A.

doi:10.1016/0006-8993(95)00276-v

Cited by 222 publications

(177 citation statements)

References 112 publications

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“…We found NTS NPY but not POMC neurons innervate both liver and eWAT, and thus, they may be part of the common outflow to liver and eWAT. Finally, we identified dual-labeled neurons in the A5 region, an area containing catecholaminergic neurons, that have been implicated in sympathetic outflow to many organs (27,36). Our findings also confirm those from prior tracing studies from white fat or liver in other species (9,19).…”

Section: Discussionsupporting

confidence: 86%

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Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically

Stanley

Pinto

Segal

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

159

134

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The autonomic nervous system regulates fuel availability and energy storage in the liver, adipose tissue, and other organs; however, the molecular components of this neural circuit are poorly understood. We sought to identify neural populations that project from the CNS indirectly through multisynaptic pathways to liver and epididymal white fat in mice using pseudorabies virus strains expressing different reporters together with BAC transgenesis and immunohistochemistry. Neurons common to both circuits were identified in subpopulations of the paraventricular nucleus of the hypothalamus (PVH) by double labeling with markers expressed in viruses injected in both sites. The lateral hypothalamus and arcuate nucleus of the hypothalamus and brainstem regions (nucleus of the solitary tract and A5 region) also project to both tissues but are labeled at later times. Connections from these same sites to the PVH were evident after direct injection of virus into the PVH, suggesting that these regions lie upstream of the PVH in a common pathway to liver and adipose tissue (two metabolically active organs). These common populations of brainstem and hypothalamic neurons express neuropeptide Y and proopiomelanocortin in the arcuate nucleus, melanin-concentrating hormone, and orexin in the lateral hypothalamus and in the corticotrophin-releasing hormone and oxytocin in the PVH. The delineation of this circuitry will facilitate a functional analysis of the possible role of these potential commandlike neurons to modulate autonomic outflow and coordinate metabolic responses in liver and adipose tissue.autonomic nervous system | neuronal tracing | pseudorabies virus T he autonomic nervous system plays a prominent role in modulating carbohydrate and lipid metabolism. The original theories of sympathetic activation (1) proposed a body-wide increase in sympathetic outflow. However, later studies suggested differential sympathetic activation on specific organs through distinct autonomic projections, which permits more finely tuned control of metabolism (2, 3).The liver and adipose tissue play important roles in fuel storage and release. These organs respond to altered energy availability with a set of homeostatic responses mediated by humoral factors and autonomic outflow. For example, activation of hepatic sympathetic aminergic and peptidergic innervation increases glucose output and modulates fatty acid transport. Conversely, parasympathetic activity decreases hepatic glucose output and increases carbohydrate storage (4). Likewise, the sympathetic innervation of white adipose tissue induces lipolysis (5) and alters glucose uptake. Thus, in general, parasympathetic activity favors fuel storage, whereas sympathetic activity increases the fuel available for immediate use.Many CNS regions regulate autonomic outflow to hepatic or adipose tissue to influence peripheral energy homeostasis. In particular, the ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), lateral hypothalamus (LH), and nucleus of the solitary tract (NTS) (6)...

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Section: Discussionsupporting

confidence: 86%

“…Within the PVH, dual-labeled neural subpopulations express CRH and OT. These populations have also been implicated in autonomic outflow through the stellate ganglion (27). In addition, both intracerebral CRH and OT modify autonomic activity (28,29).…”

Section: Discussionmentioning

confidence: 99%

Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically

Stanley

Pinto

Segal

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

159

134

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“…Thus, such neurons appear to be pluripotent with regard to their ability to sense and integrate signals relating to the metabolic status of the periphery. Given their connections with autonomic and hypophysial output pathways (10,(57)(58)(59)(60), ARC NPY and POMC neurons represent a class of neurons that is uniquely equipped to act as a central clearing station for such information.…”

Section: Discussionmentioning

confidence: 99%

Localization of glucokinase gene expression in the rat brain.

et al. 2000

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The brain contains a subpopulation of glucosensing neurons that alter their firing rate in response to elevated glucose concentrations. In pancreatic ␤-cells, glucokinase (GK), the rate-limiting enzyme in glycolysis, mediates glucose-induced insulin release by regulating intracellular ATP production. A similar role for GK is proposed to underlie neuronal glucosensing. Via in situ hybridization, GK mRNA was localized to hypothalamic areas that are thought to contain relatively large populations of glucosensing neurons (the arcuate, ventromedial, dorsomedial, and paraventricular nuclei and the lateral area). GK also was found in brain areas without known glucosensing neurons (the lateral habenula, the bed nucleus stria terminalis, the inferior olive, the retrochiasmatic and medial preoptic areas, and the thalamic posterior paraventricular, interpeduncular, oculomotor, and anterior olfactory nuclei). Conversely, GK message was not found in the nucleus tractus solitarius, which contains glucosensing neurons, or in ependymal cells lining the third ventricle, where others have described its presence. In the arcuate nucleus, >75% of neuropeptide Y-positive neurons also expressed GK, and most GK + neurons also expressed KIR6.2 (the pore-forming subunit of the ATP-sensitive K + channel). The anatomic distribution of GK mRNA was confirmed in micropunch samples of hypothalamus via reverse transcription-polymerase chain reaction (RT-PCR). Nucleotide sequencing of the recovered PCR product indicated identity with nucleotides 1092-1411 (within exon 9 and 10) of hepatic and ␤-cell GK. The specific anatomic localization of GK mRNA in hypothalamic areas known to contain glucosensing neurons and the coexpression of KIR6.2 and NPY in GK + neurons support a role for GK as a primary determinant of glucosensing in neuropeptide neurons that integrate multiple signals relating to peripheral energy metabolism. Diabetes 49:693-700, 2000 M ammalian feeding behavior and general energy homeostasis appear to be regulated by circulating levels of nutrients (glucose) and peptides (e.g., leptin, insulin). Sensors to detect levels of these factors have been found to reside within specific nuclei of the hypothalamus (1-8), where central regulation of energy homeostasis is believed to be coordinated. For example, large changes in blood glucose are correlated with centrally mediated responses such as thermogenesis through activation of the sympathetic nervous system. These changes are monitored by the brain (9-11), and such responses are altered in obesity-prone animals (11-13). Moreover, lesions of the ventromedial hypothalamus (VMH) prevent the hypoglycemic activation of the sympathetic response (14). Thus, available data indicate that glucose detection by hypothalamic neurons may play an important role in regulating energy homeostasis.Glucosensing neurons are among the best characterized of such metabolic sensors. Unlike most neurons, they use glucose as a signaling molecule to alter their firing rate in response to changes in ambient glucose le...

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“…Because pH-sensitive RTN neurons are located near the ventral surface of the RTN and extend projections along the marginal layer (Mulkey et al, 2004), the presence within this layer of large numbers of serotonergic terminals containing substance P strongly suggests that these chemosensitive neurons receive at least part of their serotonergic input from raphe pallidus, obscurus, or the parapyramidal area, which are the only raphe subdivisions that express preprotachykinin A (Sasek et al, 1990;Jansen et al, 1995;Li et al, 2005). However, even within these subdivisions of the medullary raphe, retrogradely labeled serotonergic neurons were still very scattered.…”

Section: Origin Of the Serotonergic Innervation Of Rtnmentioning

confidence: 99%

“…TRH-expressing serotonergic neurons innervate a large fraction of the brainstem and spinal cord, including regions involved in autonomic regulation (Batten, 1995;Jansen et al, 1995;Sun et al, 1995;Talley et al, 2000). These neurons are a plausible source of the TRH innervation of RTN.…”

Section: Origin Of the Serotonergic Innervation Of Rtnmentioning

confidence: 99%

Serotonergic Neurons Activate Chemosensitive Retrotrapezoid Nucleus Neurons by a pH-Independent Mechanism

Mulkey¹,

Rosin²,

West³

et al. 2007

J. Neurosci.

140

188

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Serotonin activates respiration and enhances the stimulatory effect of CO 2 on breathing. The present study tests whether the mechanism involves the retrotrapezoid nucleus (RTN), a group of medullary glutamatergic neurons activated by extracellular brain pH and presumed to regulate breathing. We show that the RTN is innervated by both medullary and pontine raphe and receives inputs from thyrotropin-releasing hormone (TRH) and substance P-expressing neurons. Coexistence of serotonin and substance P in terminals within RTN confirmed that lower medullary serotonergic neurons innervate RTN. In vivo, unilateral injection of serotonin into RTN stimulated inspiratory motor activity, and pH-sensitive RTN neurons were activated by iontophoretic application of serotonin or substance P. In brain slices, pH-sensitive RTN neurons were activated by serotonin, substance P, and TRH. The effect of serotonin in slices was ketanserin sensitive and persisted in the presence of glutamate, GABA, glycine, and purinergic ionotropic receptor antagonists. Serotonin and pH had approximately additive effects on the discharge rate of RTN neurons, both in slices and in vivo. In slices, serotonin produced an inward current with little effect on conductance and had no effect on the pH-induced current. We conclude that (1) RTN receives input from multiple raphe nuclei, (2) serotonin, substance P, and TRH activate RTN chemoreceptors, and (3) excitatory effects of serotonin and pH are mediated by distinct ionic conductances. Thus, RTN neurons presumably contribute to the respiratory stimulation caused by serotonergic neurons, but serotonin seems without effect on the cellular mechanism by which RTN neurons detect pH.

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Transneuronal labeling of CNS neuropeptide and monoamine neurons after pseudorabies virus injections into the stellate ganglion

Cited by 222 publications

References 112 publications

Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically

Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically

Localization of glucokinase gene expression in the rat brain.

Serotonergic Neurons Activate Chemosensitive Retrotrapezoid Nucleus Neurons by a pH-Independent Mechanism

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