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Regulated Intron Removal Integrates Motivational State and Experience.

ABSTRACT: Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen identified pasilla, the fly ortholog of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single-nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.

SUBMITTER: Gill J

PROVIDER: S-EPMC5527978 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Regulated Intron Removal Integrates Motivational State and Experience.

Gill Jason J Park Younshim Y McGinnis J P JP Perez-Sanchez Consuelo C Blanchette Marco M Si Kausik K

Cell 20170501 5

Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-cod ...[more]

PMID: 28525754

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Project description:BACKGROUND:An unresolved debate lingers over the effect of past behavior on motivational patterns and future behavior stability in the exercise context. Theorists argue that past behavior has a residual effect on future behavior; however, empirical studies have shown that past behavior displays significant power in predicting behavior recurrence in the future. The present research aimed to examine the effect of past behavior and motivational determinants on future exercise adherence. METHODS:Data from 437 Portuguese gym exercisers (female = 235; male = 202) aged between 18 and 53 years (M = 31.14; SD = 9.47), with exercise experience ranging from 6 to 12 months (M = 9.41; SD = 1.33) were considered for research. Participants completed a multi-section survey measuring interpersonal behaviors, basic psychological needs, behavioral regulations, and intentions. Data from past behavior and future exercise adherence were collected using computerized records of their attendance at the gym. RESULTS:Positive and significant correlations paths were evidenced among perceived supportive behaviors, needs satisfaction, autonomous motivation, intentions and future exercise adherence. Similar results were presented among perceived thwarting behaviors, needs frustration, and controlled motivation. Regression paths showed that perceived supportive behavior, basic needs satisfaction, and autonomous motivation displayed positive and significant effects on future behaviors; thus, past behavior displayed the highest coefficient on future exercise adherence. Fitness professionals should aim at creating supportive environments, thus, improving the likelihood of being perceived by exercisers as need-supportive individuals. By doing so, as a result, exercisers would experience increased levels of autonomous motivation and higher rates of future exercise attendance at the gym. Hence, exercisers will gradually form their positive past exercise experience, increasing the probability of engaging in an exercise in the future.

Project description:To investigate the relationship between hypercholesterolemia, foam cell formation and inflammation, we performed lipidomic and transcriptomic analyses of elicited peritoneal macrophages in wild type (WT) or LDL receptor knockout (LDLR KO) mice fed either a normal cholesterol, normal fat (NCNF) diet or a high cholesterol, high fat (HCHF) 'Western' style diet. The combination of the LDLR KO genotype and the HCHF diet results in the formation of macrophage foam cells in the elicited peritoneal macrophage population. Analysis of macrophages from the above four experimental groups revealed massive reprogramming of the lipidome in response to both diet and genotype. These studies confirmed and extended prior knowledge regarding the roles of SREBP and LXR signaling in cholesterol and fatty acid homeostasis. Unexpectedly, peritoneal macrophage foam cells exhibited a strongly 'deactivated' phenotype, with marked suppression of pro-inflammatory mediators that are normally characteristic of the inflammatory responses associated with atherosclerotic lesions. Many of these changes in gene expression and lipid metabolism appear to be related to the paradoxical accumulation of high levels of desmosterol, the last intermediate in the Bloch pathway of cholesterol biosynthesis. WT or LDLR KO mice were fed either a NCNF diet or a HCHF diet for twelve weeks to establish four experimental groups (WT-NCNF diet, WT-HCHF diet, KO-NCNF diet, and KO-HCHF diet). As expected, the combination of the HCHF diet and LDLR KO genotype resulted in a synergistic effect on serum lipid levels. Elicited peritoneal macrophages (92-96% F4/80-positive) were immediately prepared for analysis, thereby preserving in vivo gene expression and lipid profiles. Macrophages derived from LDLR KO mice fed the HCHF diet contained nearly four-fold more total cholesterol than cells from WT mice fed the same diet. Quantitative analysis of 245 lipid species revealed significant changes in nearly all major lipid classes. Using a two-way ANOVA model, we found that 176 (72%) of the lipids analyzed were significantly affected by the HCHF diet, 133 (54%) by the LDLR KO genotype, and 114 (46%) by interactions between the HCHF diet and LDLR KO genotype. Many of the observed interactions (60%) were synergistic.

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Regulated Intron Removal Integrates Motivational State and Experience.

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Regulated Intron Removal Integrates Motivational State and Experience.

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