Conditioned Taste and Place Preferences Induced by Electrical Stimulation of the External Lateral Parabrachial Nucleus: A General Reinforcing Mechanism?

Abstract The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN.

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Rapid stimulation of sodium intake combining aldosterone into the 4th ventricle and the blockade of the lateral parabrachial nucleus

Neuroscience ◽

10.1016/j.neuroscience.2017.01.005 ◽

2017 ◽

Vol 346 ◽

pp. 94-101 ◽

Cited By ~ 1

Author(s):

S. Gasparini ◽

M.R. Melo ◽

G.F. Leite ◽

P.A. Nascimento ◽

G.M.F. Andrade-Franzé ◽

...

Keyword(s):

Sodium Intake ◽

Parabrachial Nucleus ◽

Lateral Parabrachial Nucleus ◽

Rapid Stimulation ◽

4Th Ventricle ◽

Stimulation Of

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Hyperglycemia induced by electrical stimulation of lateral part of dorsal parabrachial nucleus

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.254.4.e468 ◽

1988 ◽

Vol 254 (4) ◽

pp. E468-E475

Author(s):

T. Fujiwara ◽

K. Nagai ◽

S. Takagi ◽

H. Nakagawa

Keyword(s):

Electrical Stimulation ◽

Glucagon Secretion ◽

Light Period ◽

Parabrachial Nucleus ◽

Lateral Part ◽

Beta Adrenergic ◽

Adrenergic Mechanism ◽

Adrenergic Blocker ◽

Bilateral Lesions ◽

Stimulation Of

Electrical stimulation of the lateral part of the dorsal parabrachial nucleus (PBD) induces hyperglycemia by enhancing glucagon secretion and suppressing insulin secretion in rats. The mechanism of this effect in the light period was examined by use of blockers of the autonomic nervous system. Hexamethonium, a ganglion blocker, and propranolol, a beta-adrenergic blocker, markedly inhibited the hyperglycemic response to stimulation of the lateral part of the PBD (LPBD). In contrast, phenoxybenzamine, an alpha-adrenergic blocker, and atropine methylnitrate, a muscarinic blocker, had no effect. Because previous studies showed that bilateral lesions of the suprachiasmatic nucleus (SCN) eliminated hyperglycemia induced by intracranial injection of 2-deoxy-D-glucose and that blinding largely suppressed the hyperglycemia, the effects of these two treatments on hyperglycemia induced by electrical stimulation of the LPBD were examined. SCN lesions abolished the hyperglycemic response but did not affect the hyperglucagonemic response. Results 4 wk after orbital enucleation were similar to those after SCN lesions. These findings suggest that the SCN and a beta-adrenergic mechanism are involved in the hyperglycemic response to LPBD stimulation.

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Expression of c-fos protein in rat brain elicited by electrical stimulation of the pontine parabrachial nucleus

Journal of Neuroscience ◽

10.1523/jneurosci.12-09-03582.1992 ◽

1992 ◽

Vol 12 (9) ◽

pp. 3582-3590 ◽

Cited By ~ 94

Author(s):

TL Krukoff ◽

TL Morton ◽

KH Harris ◽

JH Jhamandas

Keyword(s):

Electrical Stimulation ◽

Rat Brain ◽

Parabrachial Nucleus ◽

Fos Protein ◽

Stimulation Of

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Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

Endocrinology ◽

10.1210/en.2015-2081 ◽

2016 ◽

Vol 157 (6) ◽

pp. 2380-2392 ◽

Cited By ~ 11

Author(s):

Yang Liu ◽

Ying Huang ◽

Tiemin Liu ◽

Hua Wu ◽

Huxing Cui ◽

...

Keyword(s):

Food Intake ◽

Parabrachial Nucleus ◽

Designer Drug ◽

Male Mice ◽

Moderate Dose ◽

Related Peptide ◽

Lateral Parabrachial Nucleus ◽

Melanocortin 4 Receptor ◽

Double Immunohistochemistry ◽

Stimulation Of

Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia.

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