scholarly journals TrkB-expressing paraventricular hypothalamic neurons suppress appetite through multiple neurocircuits

2019 ◽  
Author(s):  
Juan Ji An ◽  
Clint E. Kinney ◽  
Guey-Ying Liao ◽  
Eric J. Kremer ◽  
Baoji Xu
Keyword(s):  
Energy Balance ◽  
Severe Obesity ◽  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Neuronal Population ◽  
Parabrachial Nucleus ◽  
Trkb Receptor ◽  
Lateral Parabrachial Nucleus ◽  
Its Gene ◽  
Neural Substrate

ABSTRACTThe TrkB receptor is critical for the control of energy balance, as mutations in its gene (NTRK2) lead to hyperphagia and severe obesity in humans and mice. The main neural substrate mediating the appetite-suppressing activity of TrkB, however, remains unknown. Here, we demonstrate that selective Ntrk2 deletion within the paraventricular hypothalamus (PVH) leads to severe hyperphagic obesity. Furthermore, chemogenetic activation or inhibition of TrkB-expressing PVH (PVHTrkB) neurons suppresses or increases food intake, respectively. PVHTrkB neurons project to multiple brain regions, including the ventromedial hypothalamus (VMH) and the lateral parabrachial nucleus (LPBN). We found that PVHTrkB neurons projecting to LPBN are distinct from those projecting to VMH, yet Ntrk2 deletion in PVH neurons projecting to either VMH or LPBN results in hyperphagia and obesity. Therefore, TrkB signaling is a key regulator of a previously uncharacterized and heterogenous neuronal population within the PVH that impinges upon multiple circuits to govern appetite.

scholarly journals Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

2019 ◽  
Author(s):  
Michael C. Chiang ◽  
Eileen K. Nguyen ◽  
Andrew E. Papale ◽  
Sarah E. Ross
Keyword(s):  
Ventromedial Hypothalamus ◽  
Parabrachial Nucleus ◽  
Projection Neurons ◽  
Pain Response ◽  
Neural Pathways ◽  
Bed Nucleus ◽  
Lateral Parabrachial Nucleus ◽  
Efferent Projections ◽  
Efferent Neurons ◽  
Nociceptive Input

ABSTRACTThe lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.HIGHLIGHTSSpatially segregated neurons in the lPBN collateralize to distinct targets.Distinct output pathways give rise to separate aspects of the pain response.Dynorphin neurons within the lPBN convey noxious information across subdivisions.eTOC BLURBChiang et al. reveal that neurons in spatially segregated regions of the lateral parabrachial nucleus collateralize to distinct targets, and that activation of distinct efferents gives rise to separate components of the nocifensive response.

Glucagon-Like Peptide-1-, but not Growth and Differentiation Factor 15-, Receptor Activation Increases the Number of Interleukin-6-Expressing Cells in the External Lateral Parabrachial Nucleus

2019 ◽  
Vol 109 (4) ◽  
pp. 310-321 ◽  
Author(s):  
Fredrik Anesten ◽  
Devesh Mishra ◽  
Adrià Dalmau Gasull ◽  
Linda Engström-Ruud ◽  
Jakob Bellman ◽  
...  
Keyword(s):  
Energy Balance ◽  
Mrna Level ◽  
Intraperitoneal Administration ◽  
Receptor Activation ◽  
Parabrachial Nucleus ◽  
Differentiation Factor ◽  
Lateral Parabrachial Nucleus ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Anorexigenic Peptide

Interleukin (IL)-6 in the hypothalamus and hindbrain is an important downstream mediator of suppression of body weight and food intake by glucagon-like peptide-1 (GLP-1) receptor stimulation. CNS GLP-1 is produced almost exclusively in prepro-glucagon neurons in the nucleus of the solitary tract. These neurons innervate energy balance-regulating areas, such as the external lateral parabrachial nucleus (PBNel); essential for induction of anorexia. Using a validated novel IL-6-reporter mouse strain, we investigated the interactions in PBNel between GLP-1, IL-6, and calcitonin gene-related peptide (CGRP, a well-known mediator of anorexia). We show that PBNel GLP-1R-containing cells highly (to about 80%) overlap with IL-6-containing cells on both protein and mRNA level. Intraperitoneal administration of a GLP-1 analogue exendin-4 to mice increased the proportion of IL-6-containing cells in PBNel 3-fold, while there was no effect in the rest of the lateral parabrachial nucleus. In contrast, injections of an anorexigenic peptide growth and differentiation factor 15 (GDF15) markedly increased the proportion of CGRP-containing cells, while IL-6-containing cells were not affected. In summary, GLP-1R are found on IL-6-producing cells in PBNel, and GLP-1R stimulation leads to an increase in the proportion of cells with IL-6-reporter fluorescence, supporting IL-6 mediation of GLP-1 effects on energy balance.

scholarly journals Central Noradrenergic Neurotransmission and Weight Loss 6 Months After Gastric Bypass Surgery in Patients with Severe Obesity

2021 ◽  
Author(s):  
J. Marvin Soeder ◽  
Julia Luthardt ◽  
Michael Rullmann ◽  
Georg A. Becker ◽  
Mohammed K. Hankir ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Severe Obesity ◽  
Occipital Cortex ◽  
Brain Regions ◽  
General Tendency ◽  
Strong Positive Correlation ◽  
Reference Tissue ◽  
Efficient Treatment ◽  
Post Surgery

Abstract Purpose Roux-en-Y gastric bypass (RYGB) surgery is currently the most efficient treatment to achieve long-term weight loss in individuals with severe obesity. This is largely attributed to marked reductions in food intake mediated in part by changes in gut-brain communication. Here, we investigated for the first time whether weight loss after RYGB is associated with alterations in central noradrenaline (NA) neurotransmission. Materials and Methods We longitudinally studied 10 individuals with severe obesity (8 females; age 43.9 ± 13.1 years; body mass index (BMI) 46.5 ± 4.8 kg/m2) using (S,S)-[11C]O-methylreboxetine and positron emission tomography to estimate NA transporter (NAT) availability before and 6 months after surgery. NAT distribution volume ratios (DVR) were calculated by volume-of-interest analysis and the two-parameter multilinear reference tissue model (reference region: occipital cortex). Results The participants responded to RYGB surgery with a reduction in BMI of 12.0 ± 3.5 kg/m2 (p < 0.001) from baseline. This was paralleled by a significant reduction in DVR in the dorsolateral prefrontal cortex (pre-surgery 1.12 ± 0.04 vs. post-surgery 1.07 ± 0.04; p = 0.019) and a general tendency towards reduced DVR throughout the brain. Furthermore, we found a strong positive correlation between pre-surgery DVR in hypothalamus and the change in BMI (r = 0.78; p = 0.01). Conclusion Reductions in BMI after RYGB surgery are associated with NAT availability in brain regions responsible for decision-making and homeostasis. However, these results need further validation in larger cohorts, to assess whether brain NAT availability could prognosticate the outcome of RYGB on BMI. Graphical abstract

scholarly journals GLP-1 Receptor Stimulation of the Lateral Parabrachial Nucleus Reduces Food Intake: Neuroanatomical, Electrophysiological, and Behavioral Evidence

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4356-4367 ◽  
Author(s):  
Jennifer E. Richard ◽  
Imre Farkas ◽  
Fredrik Anesten ◽  
Rozita H. Anderberg ◽  
Suzanne L. Dickson ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Parabrachial Nucleus ◽  
Lateral Parabrachial Nucleus ◽  
Electrophysiological Studies ◽  
Glucagon Like Peptide 1 ◽  
Behavioral Evidence ◽  
Stimulation Of

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.

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

Neuroscience ◽  
2017 ◽  
Vol 346 ◽  
pp. 94-101 ◽  
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

scholarly journals Proteolytic Remodeling of Perineuronal Nets: Effects on Synaptic Plasticity and Neuronal Population Dynamics

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
P. Lorenzo Bozzelli ◽  
Seham Alaiyed ◽  
Eunyoung Kim ◽  
Sonia Villapol ◽  
Katherine Conant
Keyword(s):  
Population Dynamics ◽  
Synaptic Plasticity ◽  
Synaptic Input ◽  
Neuronal Plasticity ◽  
Population Level ◽  
Gamma Oscillations ◽  
Brain Regions ◽  
Neuronal Population ◽  
Perineuronal Nets ◽  
Perineuronal Net

The perineuronal net (PNN) represents a lattice-like structure that is prominently expressed along the soma and proximal dendrites of parvalbumin- (PV-) positive interneurons in varied brain regions including the cortex and hippocampus. It is thus apposed to sites at which PV neurons receive synaptic input. Emerging evidence suggests that changes in PNN integrity may affect glutamatergic input to PV interneurons, a population that is critical for the expression of synchronous neuronal population discharges that occur with gamma oscillations and sharp-wave ripples. The present review is focused on the composition of PNNs, posttranslation modulation of PNN components by sulfation and proteolysis, PNN alterations in disease, and potential effects of PNN remodeling on neuronal plasticity at the single-cell and population level.

scholarly journals Lateral parabrachial nucleus and opioid mechanisms of the central nucleus of the amygdala in the control of sodium intake

2017 ◽  
Vol 316 ◽  
pp. 11-17 ◽  
Author(s):  
Gláucia M.F. Andrade-Franzé ◽  
Silvia Gasparini ◽  
Laurival A. De Luca ◽  
Patrícia M. De Paula ◽  
Débora S.A. Colombari ◽  
...  
Keyword(s):  
Sodium Intake ◽  
Central Nucleus ◽  
Parabrachial Nucleus ◽  
Lateral Parabrachial Nucleus ◽  
Opioid Mechanisms

The lateral parabrachial nucleus controls hypertonic, not isotonic, NaCl intake

Appetite ◽  
2008 ◽  
Vol 51 (2) ◽  
pp. 362
Author(s):  
L.A. De Luca ◽  
R.B. David ◽  
A. Godino ◽  
L.M. Vivas ◽  
J. Antunes-Odrigues ◽  
...  
Keyword(s):  
Parabrachial Nucleus ◽  
Lateral Parabrachial Nucleus
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