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.

scholarly journals Divergent Neural Pathways Emanating from the Lateral Parabrachial Nucleus Mediate Distinct Components of the Pain Response

Neuron ◽  
2020 ◽  
Vol 106 (6) ◽  
pp. 927-939.e5 ◽  
Author(s):  
Michael C. Chiang ◽  
Eileen K. Nguyen ◽  
Martha Canto-Bustos ◽  
Andrew E. Papale ◽  
Anne-Marie M. Oswald ◽  
...  
Keyword(s):  
Parabrachial Nucleus ◽  
Pain Response ◽  
Neural Pathways ◽  
Lateral Parabrachial Nucleus

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.

Lateral parabrachial subnucleus lesions abolish feeding induced by mercaptoacetate but not by 2-deoxy-D-glucose

1993 ◽  
Vol 265 (5) ◽  
pp. R1168-R1178 ◽  
Author(s):  
N. Y. Calingasan ◽  
S. Ritter
Keyword(s):  
Area Postrema ◽  
Ibotenic Acid ◽  
Metabolic Inhibitors ◽  
Parabrachial Nucleus ◽  
Cresyl Violet ◽  
Neural Pathways ◽  
Lateral Parabrachial Nucleus ◽  
Cresyl Violet Staining ◽  
Electrolytic Lesions ◽  
Pass Through

Lesions of the area postrema/nucleus of the solitary tract (AP/NTS) region abolish feeding induced by mercaptoacetate (MA) and 2-deoxy-D-glucose (2DG), metabolic inhibitors that selectively impair fatty acid and glucose utilization, respectively. Because the AP/NTS region is important for both MA- and 2DG-induced feeding, the present experiment investigated the involvement of the lateral parabrachial nucleus (1PBN), which is innervated by AP/NTS neurons, in these feeding responses. Electrolytic and ibotenic acid lesions were directed at the entire parabrachial nucleus or at specific lateral parabrachial subnuclei. Rats with electrolytic lesions were tested for feeding in response to 0.9% NaCl (subcutaneous or intraperitoneal), MA (400, 600, and 800 mumol/kg ip), and 2DG (100 and 200 mg/kg sc). Ibotenate-lesioned rats were tested with NaCl and MA only. Lesions were verified either by cresyl violet staining or by glial fibrillary acidic protein immunohistochemistry. Bilateral destruction of the 1PBN severely impaired or abolished MA-induced feeding. Cell bodies important for MA-induced feeding appear to be localized in the dorsal-central 1PBN subnuclear area, because both electrolytic and cytotoxin microlesions centered in this area abolished feeding in response to MA. Fibers of passage important for MA-induced feeding appear to pass through the external and superior 1PBN because electrolytic but not cytotoxin lesions of these subnuclei disrupted the feeding response. In contrast, 2DG-induced feeding did not differ significantly from sham-lesioned controls in any of the 1PBN lesion groups. These results indicate that 2DG and MA stimulate feeding by activating separate central neural pathways and, perhaps, distinct metabolic controls of food intake.

scholarly journals A spinoparabrachial circuit defined by Tacr1 expression drives pain

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Arnab Barik ◽  
Anupama Sathyamurthy ◽  
James H Thompson ◽  
Mathew Seltzer ◽  
Ariel J Levine ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Negative Emotions ◽  
Parabrachial Nucleus ◽  
Projection Neurons ◽  
Spinal Neurons ◽  
Lateral Parabrachial Nucleus ◽  
Ongoing Pain ◽  
And Behaviors ◽  
Noxious Stimuli ◽  
Pain Responses

Painful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here we describe a pathway from spinal cord to brain for ongoing pain. Activation of a subset of spinal neurons expressing Tacr1 evokes a full repertoire of somatotopically-directed pain-related behaviors in the absence of noxious input. Tacr1 projection neurons (expressing NKR1) target a tiny cluster of neurons in the superior lateral parabrachial nucleus (PBN-SL). We showed that these neurons, which also express Tacr1 (PBN-SLTacr1), are responsive to sustained but not acute noxious stimuli. Activation of PBN-SLTacr1 neurons alone did not trigger pain responses but instead served to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SLTacr1 neurons ignored long-lasting noxious stimuli. Together, these data reveal new details about this spinoparabrachial pathway and its key role in the sensation of ongoing pain.

scholarly journals A spinoparabrachial circuit defined by Tacr1 expression drives pain

2020 ◽  
Author(s):  
Arnab Barik ◽  
Anupama Sathyamurthy ◽  
James Thompson ◽  
Mathew Seltzer ◽  
Ariel Levine ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Negative Emotions ◽  
Parabrachial Nucleus ◽  
Projection Neurons ◽  
Coping Behaviors ◽  
Lateral Parabrachial Nucleus ◽  
Spinal Projection ◽  
Ongoing Pain ◽  
And Behaviors ◽  
Noxious Stimuli

AbstractPainful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here we describe a pathway from spinal cord to brain for ongoing pain. Activation of a defined subset of spinal projection neurons expressing Tacr1 evokes a full repertoire of somatotopically-directed coping behaviors in the absence of noxious input. These cells project to a tiny cluster of Tacr1-positive neurons in the superior lateral parabrachial nucleus (PBN-SL) that themselves are responsive to sustained but not acute noxious stimuli. Activation of these PBN-SLTacr1 neurons alone does not trigger pain responses but instead serves to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SLTacr1 neurons ignore long-lasting noxious stimuli. These data reveal a spinoparabrachial pathway that plays a key role in the sensation of ongoing pain.

scholarly journals Enhanced synaptic transmission in the extended amygdala and altered excitability in an extended amygdala to brainstem circuit in a Dravet syndrome mouse model

2020 ◽  
Author(s):  
Wen Wei Yan ◽  
Maya Xia ◽  
Alyssa Levitt ◽  
Nicole Hawkins ◽  
Jennifer Kearney ◽  
...  
Keyword(s):  
Sudden Death ◽  
Early Onset ◽  
Dravet Syndrome ◽  
Parabrachial Nucleus ◽  
Projection Neurons ◽  
Stria Terminalis ◽  
Respiratory Dysfunction ◽  
Bed Nucleus ◽  
Extended Amygdala ◽  
Spontaneous Seizures

ABSTRACTObjectiveDravet syndrome (DS) is a severe, early-onset epilepsy with an increased incidence of sudden death. Evidence of interictal breathing deficits in DS suggest that alterations in subcortical projections to brainstem nuclei may exist, which might be driving comorbidities in DS. The aim of this study was to determine if a subcortical structure, the bed nucleus of the stria terminalis (BNST) in the extended amygdala, is activated by seizures, exhibits changes in excitability, and expresses any alterations in neurons projecting to a brainstem nucleus associated with respiration, stress response and homeostasis.MethodsExperiments were conducted using F1 mice generated by breeding 129.Scn1a+/- mice with wildtype C57BL/6J mice. Immunohistochemistry was performed to quantify neuronal c-fos activation in DS mice after observed spontaneous seizures. Whole cell patch clamp and current clamp electrophysiology recordings were conducted to evaluate changes in intrinsic and synaptic excitability in the BNST.ResultsSpontaneous seizures in DS mice significantly enhanced neuronal c-fos expression in the BNST. Further, the BNST had altered AMPA/NMDA postsynaptic receptor composition and showed changes in spontaneous neurotransmission, with greater excitation and decreased inhibition. BNST to parabrachial nucleus (PBN) projection neurons exhibited intrinsic excitability in wildtype mice, while these projection neurons were hypoexcitable in DS mice.SignificanceThe findings suggest that there is altered excitability in neurons of the BNST, including BNST to PBN projection neurons, in DS mice. These alterations could potentially be driving comorbid aspects of DS outside of seizures, including respiratory dysfunction and sudden death.SIGNIFICANCE STATEMENTDravet syndrome (DS) is an early-onset epilepsy with an increased risk of sudden death. We determined that there are alterations in a subcortical nucleus, the bed nucleus of the stria terminalis (BNST) of the extended amygdala, in a murine DS model. The BNST is involved in stress, anxiety, feeding, and respiratory function. We found enhanced activation in the BNST after seizures and alterations in basal synaptic neurotransmission–with enhanced spontaneous excitatory and decreased spontaneous inhibitory postsynaptic events. Evaluating those neurons that project to the parabrachial nucleus (PBN), a nucleus with multiple homeostatic roles, we found them to be hypoexcitable in DS. Alterations in BNST to brainstem projections could be implicated in comorbid aspects of DS, including respiratory dysfunction and sudden death.

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 Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior

2018 ◽  
Vol 115 (45) ◽  
pp. E10730-E10739 ◽  
Author(s):  
Bokyeong Kim ◽  
Sehyoun Yoon ◽  
Ryuichi Nakajima ◽  
Hyo Jin Lee ◽  
Hee Jeong Lim ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Inhibitory Neurons ◽  
Stria Terminalis ◽  
Neural Pathways ◽  
Impulsive Behavior ◽  
Central Amygdala ◽  
Dopamine System ◽  
Addictive Disorders ◽  
Bed Nucleus

Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2−/−)normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA → BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.

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