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An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory
Edwards CM, Guerrero IE, Thompson D, Dolezel T, Rinaman L (2024) An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory. bioRxiv 2024.04.09.588717. doi: 10.1101/2024.04.09.588717 PMID: 38645069
Objective: To investigate the role of a gut vagal afferent-to-central noradrenergic pathway in modulating the retrieval of conditioned passive avoidance memory in rats.
Summary: This study explores how visceral sensory feedback via vagal afferents and central noradrenergic neurons influences passive avoidance memory retrieval. By lesioning specific neural pathways in adult male rats, the researchers demonstrate that disruption of these circuits significantly increased conditioned passive avoidance behavior, suggesting a critical role for these pathways in integrating interoceptive signals with contextual cues to modulate learned avoidance behaviors.
Usage: 250 ng of CCK-SAP (IT-31) was bilaterally injected into the nodose ganglion to selectively lesion gastrointestinal vagal afferents. 80 ng of Anti-DBH-SAP (IT-03) was injected bilaterally into the ventrolateral bed nucleus of the stria terminalis (vlBNST) to selectively lesion noradrenergic inputs to the anterior vlBNST.
Related Products: CCK-SAP (Cat. #IT-31), Anti-DBH-SAP (Cat. #IT-03)
Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating
McDougle M, de Araujo A, Singh A, Yang M, Braga I, Paille V, Mendez-Hernandez R, Vergara M, Woodie LN, Gour A, Sharma A, Urs N, Warren B, de Lartigue G (2024) Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab 36:1-15. doi: 10.1016/j.cmet.2023.12.014 PMID: 38242133
Objective: To investigate the separate gut-brain circuits for sugar and fat reinforcement and their combined effect on overeating.
Summary: This study reveals that intestinal fats and sugars are sensed by distinct vagal populations, each engaging separate central reward circuits to cause dopamine release and reinforcement. Combining fat and sugar triggers both circuits, leading to increased dopamine efflux and promoting overeating, highlighting a subconscious drive to consume obesogenic diets.
Usage: 0.5 µl of CCK-SAP (IT-31) or Blank-SAP as a negative control (IT-21) were injected bilaterally into the nodose ganglion for selective vagal deafferentation of the upper GI tract of mice.
Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)
Sensory spinal interoceptive pathways and energy balance regulation
Münzberg H, Berthoud HR, Neuhuber WL (2023) Sensory spinal interoceptive pathways and energy balance regulation. Mol Metab 78:101817. doi: 10.1016/j.molmet.2023.101817 PMID: 37806487
Objective: To review and discuss the roles of spinal sensory pathways, specifically dorsal root ganglia (DRG) afferents, in energy balance regulation, highlighting their contributions to metabolic homeostasis in health and disease.
Summary: This comprehensive review explores the emerging significance of spinal sensory neurons, beyond traditional gut-brain and adipose tissue-to-brain signaling pathways, in regulating energy intake and metabolism. It delves into the anatomy and functions of spinal sensory pathways, emphasizing the potential of DRG afferents in providing metabolic information to the brain. The review suggests that identifying specific DRG neurons and understanding their molecular mechanisms are crucial steps toward developing targeted therapies for metabolic diseases, such as obesity, diabetes, and cancer.
Usage: The publication references that CCK-SAP (IT-31) injected into the nodose ganglia of mice and rats selectively ablates vagal afferent neurons expressing CCKA receptors.
Related Products: CCK-SAP (Cat. #IT-31)
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The gut-brain axis mediates bacterial driven modulation of reward signaling
Kim JS, Williams KC, Kirkland RA, Schade R, Freeman KG, Cawthon CR, Rautmann AW, Smith JM, Edwards GL, Glenn TC, Holmes PV, de Lartigue G, de La Serre CB (2023) The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab 26:101764. doi: 10.1016/j.molmet.2023.101764 PMID: 37380023
Objective: To investigate the role of gut microbiota and vagal signaling in modulating brain dopamine reward pathways and appetitive feeding behavior.
Summary: The study found that high-fat diet and transfer of high-fat microbiota to germ-free rats reduced dopamine signaling and motivated feeding behavior compared to chow-fed and low-fat microbiota groups. Vagal deafferentation restored dopamine signaling and feeding motivation in high-fat microbiota rats, indicating gut bacteria signals that dampen reward are vagally mediated.
Usage: Animals were injected bilaterally into the nodose ganglion with either Saporin or CCK-SAP. A pulled glass micropipette containing either CCK-SAP (240 ng/ml in 0.1 M phosphate buffer) or SAP alone was inserted under the sheath of the cervical vagus and into the NG, the injection was done with a pressure-injector into two sites (one proximal and one distal, total volume, 1 µl).
Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice
Chen CH, Tsai TC, Wu YJ, Hsu KS (2023) Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice. JCI Insight e161874. doi: 10.1172/jci.insight.161874 PMID: 37200091
Objective: This study aimed to characterize gut-to-brain signaling and brain circuitry responsible for anxiety-like behaviors in a mouse model of inflammatory bowel disease.
Summary: The researchers found that mice with experimental colitis induced by dextran sulfate sodium administration displayed increased anxiety-like behaviors, which were prevented by cutting the vagus nerve connecting the gut to the brain. Further experiments showed that silencing brain cells in the locus coeruleus that project to the basolateral amygdala reduced anxiety behaviors in the colitis mice.
Usage: CCK-SAP (250 ng/µl) or Blank-SAP (250 ng/µl) were unilaterally or bilaterally injected to rostral (0.5 µl) and caudal (0.5 µl) parts of the nodose ganglia using a beveled injection pipette controlled by a microprocessor-controlled injector at the speed of 50 nl/sec.
Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)
Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior
Krieger JP, Asker M, Van der Velden P, Börchers S, Richard JE, Maric I, Longo F, Singh A, De Larigue G, Skibicka KP (2022) Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior. Biological Psychiatry in press. doi: 10.1016/j.biopsych.2022.04.020
Objective: To determine how the sensing of gastrointestinal state affects anxiety.
Summary: Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. The article results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety.
Usage: 1.5 ul of CCK-SAP or Blank-SAP were delivered into each nodose ganglion at 250 ng/ul.
Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)
Vagal afferent cholecystokinin receptor activation is required for glucagon-like peptide-1-induced satiation
Vana V, Laerke MK, Rehfeld JF, Arnold M, Dmytriyeva O, Langhans W, Schwartz TW, Hansen HS (2022) Vagal afferent cholecystokinin receptor activation is required for glucagon-like peptide-1-induced satiation. Diabetes Obes Metab 24(2):268-280. doi: 10.1111/dom.14575
Objective: To investigate the effect of peripheral GLP-1 on food-intake control.
Summary: Endogenous CCK interacts with GLP-1 to promote satiation and that activation of the FFA1 receptor can initiate this interaction by stimulating the release of CCK.
Usage: Utilized CCK-SAP to selectively ablate the CCK receptor-expressing gastrointestinal vagal afferent neurones (VANs).
Related Products: CCK-SAP (Cat. #IT-31)
Learning of food preferences: mechanisms and implications for obesity & metabolic diseases
Berthoud HR, Morrison CD, Ackroff K, Sclafani A (2021) Learning of food preferences: mechanisms and implications for obesity & metabolic diseases. Int J Obes (Lond) 45(10):2156-2168. doi: 10.1038/s41366-021-00894-3
Objective: This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods.
Summary: There is a critical role for the vagal gut-to-brain axis in motivation and reward. An implication for obesity treatment is that bariatric surgery may alter vagal function.
Usage: Han et al. injected 0.5 µl of CCK-SAP (250 ng/µl) into the R-NG of VGlut2-ires-Cre mice.
See: Han W et al. A Neural Circuit for Gut-Induced Reward. Cell 175:665-678, 2018.
Related Products: CCK-SAP (Cat. #IT-31)
Dissection and surgical approaches to the mouse jugular-nodose ganglia
Han W, de Araujo IE (2021) Dissection and surgical approaches to the mouse jugular-nodose ganglia. STAR Protocols 2(2):100474. doi: 10.1016/j.xpro.2021.100474
Usage: Injected 0.5 µl of CCK-SAP (250 ng/µl) into the R-NG of VGlut2-ires-Cre mice.
Related Products: CCK-SAP (Cat. #IT-31)
For complete details on the use and execution of this protocol, please refer to Han et al.
See Also: Han W et al. A neural circuit for gut-induced reward. Cell 175:665-678, 2018.
Vagotomy and insights into the microbiota-gut-brain axis
Liu Y, Forsythe P (2021) Vagotomy and insights into the microbiota-gut-brain axis. Neurosci Res 168:20-27. doi: 10.1016/j.neures.2021.04.001
Objective: To review the use of vagotomy as a tool to explore the role of the vagus nerve in gut to brain signaling.
Summary: This review article is a summary of the knowledge gained from vagotomy, a surgical procedure that involves removing part of the vagus nerve. The article discusses using CCK-SAP to specifically ablate afferent vagal nerves in the gastrointestinal tract.
Usage: The article references a study by Diepenbroek et al. that used CCK-SAP in the following dosages: In vitro: each well was treated with a different dose of saporin conjugates (0, 2.4, 24, or 240 ng) for 24 h. In vivo: An equal volume (rat: 1 µl; mouse: 0.5 µl) of CCK-SAP (250 ng/µl) or Saporin (250 ng/µl) was injected at two sites rostral and caudal to the laryngeal nerve branch.
Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
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