scholarly journals Rapid stimulus-bound suppression of intake in response to an intraduodenal nonnutritive sweetener after training with nutritive sugars predicting malaise

2012 ◽  
Vol 302 (11) ◽  
pp. R1351-R1363 ◽  
Author(s):  
Lindsey A. Schier ◽  
Terry L. Davidson ◽  
Terry L. Powley
Keyword(s):  
Signaling Pathways ◽  
Taste Aversion ◽  
Lithium Chloride ◽  
Negative Feedback ◽  
Sweet Taste ◽  
Taste Stimulus ◽  
Physiol Regul Integr Comp

In a previous report (Schier et al., Am J Physiol Regul Integr Comp Physiol 301: R1557–R1568, 2011), we demonstrated with a new behavioral procedure that rats exhibit stimulus-bound suppression of intake in response to an intraduodenal (ID) bitter tastant predicting subsequent malaise. With the use of the same modified taste aversion procedure, the present experiments evaluated whether the sweet taste properties of ID stimuli are likewise detected and encoded. Thirsty rats licked at sipper spouts for hypotonic NaCl for 30 min and received brief (first 6 min) yoked ID infusions of either the same NaCl or an isomolar lithium chloride (LiCl) solution in each session. An intestinal taste cue was mixed directly into the LiCl infusate for aversion training. Results showed that rats failed to detect intestinal sweet taste alone (20 mM Sucralose) but clearly suppressed licking in response to a nutritive sweet taste stimulus (234 mM sucrose) in the intestine that had been repeatedly paired with LiCl. Rats trained with ID sucrose in LiCl subsequently generalized responding to ID Sucralose alone at test. Replicating this, rats trained with ID Sucralose in compound with 80 mM Polycose rapidly suppressed licking to the 20 mM Sucralose alone in a later test. Furthermore, ID sweet taste signaling did not support the rapid negative feedback of sucrose or Polycose on intake when their digestion and transport were blocked. Together, these results suggest that other signaling pathways and/or transporters engaged by caloric carbohydrate stimuli potentiate detection of sweet taste signals in the intestine.

scholarly journals LTD at amygdalocortical synapses as a novel mechanism for hedonic learning

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Melissa S Haley ◽  
Stephen Bruno ◽  
Alfredo Fontanini ◽  
Arianna Maffei
Keyword(s):  
Taste Aversion ◽  
Insular Cortex ◽  
Taste Stimulus ◽  
Taste Aversion Learning ◽  
Direct Role ◽  
Hedonic Value ◽  
Basolateral Nucleus ◽  
Synaptic Responses

A novel, pleasant taste stimulus becomes aversive if associated with gastric malaise, a form of learning known as conditioned taste aversion (CTA). CTA is common to vertebrates and invertebrates and is an important survival response: eating the wrong food may be deadly. CTA depends on the gustatory portion of the insular cortex (GC) and the basolateral nucleus of the amygdala (BLA) however, its synaptic underpinnings are unknown. Here we report that CTA was associated with decreased expression of immediate early genes in rat GC of both sexes, and with reduced amplitude of BLA-GC synaptic responses, pointing to long-term depression (LTD) as a mechanism for learning. Indeed, association of a novel tastant with induction of LTD at the BLA-GC input in vivo was sufficient to change the hedonic value of a taste stimulus. Our results demonstrate a direct role for amygdalocortical LTD in taste aversion learning.

scholarly journals Conditioned taste aversion and motion sickness in cats and squirrel monkeys

1990 ◽  
Vol 68 (2) ◽  
pp. 269-278 ◽  
Author(s):  
Robert A. Fox ◽  
Merylee Corcoran ◽  
Kenneth R. Brizzee
Keyword(s):  
Taste Aversion ◽  
Motion Sickness ◽  
Lithium Chloride ◽  
Conditioned Taste Aversion ◽  
Area Postrema ◽  
Conditioned Aversion ◽  
Squirrel Monkeys ◽  
The Relationship

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7 – 12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.Key words: area postrema, conditioned taste aversion, motion sickness, nausea, emesis.

Flt3/ITD Enhances Hematopoietic Cell Migration Towards Chemokine CCL2 Independent of Blocking the Negative Feedback Mechanism on Rho-Associated Kinase

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3597-3597
Author(s):  
Seiji Fukuda ◽  
Chie Onishi ◽  
Tomohiro Hirade ◽  
Mariko Abe ◽  
Takeshi Taketani ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Negative Feedback ◽  
Conflicts Of Interest ◽  
Feedback Mechanism ◽  
Hematopoietic Cell ◽  
Negative Feedback Mechanism ◽  
Chemokine Signaling ◽  
Qualitative Changes

Abstract Internal tandem duplication mutations in the Flt3 gene (Flt3/ITD) found in patients with AML is associated with extremely poor prognosis. Our previous report demonstrating Flt3/ITD-mediated enhancement of hematopoietic cell migration towards chemokine CXCL12 (SDF1) suggests that Flt3/ITD likely facilitates dissemination of AML cells in the patients. Following studies showed that CXCL12 transiently up-regulated the expression of Rho-associated kinase-1 (Rock1) but subsequently down-regulated Rock1 expression in the control cells, whereas this effect was abolished by Flt3/ITD. The results demonstrated that CXCL12 generates negative regulatory feedback on Rock1 expression to prevent excessive migration to CXCL12 in the control cells, whereas this mechanism is abrogated by Flt3/ITD, thereby inducing deregulated cell migration (Onishi et al. ASH 2012). However, it is not known if Flt3/ITD augments migration to other chemokines and whether Flt3/ITD-induced blockage of the negative feedback loop on Rock1 expression reflects a specific effect on CXCL12/CXCR4 signaling pathway or more global change by ITD-Flt3. We found that mRNA for CCR2, a receptor for chemokine CCL2, is expressed in human AML cells. Herein, we investigated the effect of Flt3/ITD on migration to CCL2 in hematopoietic cells. Expression of CCR2 was significantly higher in the M4 and M5 cases with AML compared to other FAB subtypes that are deposited in the public gene expression database. However, there was no difference in the mRNA level for CCR2 between Flt3/ITD+ and Flt3/ITDneg cases. Consistent with AML samples, expression of surface CCR2 protein in Ba/F3 cells transfected with Flt3/ITD is equivalent to the control cells lacking Flt3/ITD. While the control Flt3/ITDneg Ba/F3 cells failed to migrate towards 1, 5, 10 and 50ng/mL of CCL2, Flt3/ITD marginally but significantly enhanced the cell migration towards 5ng/mL of CCL2 in Ba/F3 cells within 4 hours compared to control. In the Flt3/ITDneg cells exposed to 5ng/mL of CCL2, the mRNA expression of Rock1 continued to increase without being down-regulated to the basal level within 4 hours, and did not show any biphasic changes. In the Flt3/ITD+ Ba/F3 cells, however, Rock1 expression was significantly elevated compared to Flt3/ITDneg cells prior to incubation with CCL2, but down-regulated to 50% of the original level by 5ng/mL of CCL2 within 30 minutes. In contrast, Rock1 expression was barely affected and remained elevated by CXCL12 in Flt3/ITD+ Ba/F3 cells. Elevated expression of CCR2 in the M4 and M5 AML suggests that CCR2 signaling pathways can regulate migration of AML cells with monocytic lineage. Similar to CXCL12, migration towards CCL2 was also enhanced by Flt3/ITD without up-regulating CCR2 expression, suggesting that the enhanced chemotaxis by Flt3/ITD is not specific to CXCL12 and likely attributed to qualitative changes in the CCL2/CCR2 signaling pathway rather than their quantitative increase. Down-regulation of Rock1 expression by CCL2 in Flt3/ITD+ Ba/F3 cells may represent one of the qualitative changes in the CCL2 signaling pathway. However, blocking the CXCL12-induced negative regulatory mechanism on Rock1 expression existing in the Flt3/ITD+ cells was not identified in the CCL2 signaling. These data indicate that while enhancement in cell migration to chemokines by Flt3/ITD is not specific to CXCL12, blocking the negative feedback mechanism on Rock1 expression is not necessarily used in other chemokine signaling pathways. Our data suggests that Flt3/ITD mutations regulate trafficking of AML cells by modulating various chemokine signaling, but divergent molecular mechanism is involved in regulating cell migration towards different chmeokines. Disclosures No relevant conflicts of interest to declare.

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