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Orbitofrontal cortex supports behavior and learning using inferred but not cached values.

ABSTRACT: Computational and learning theory models propose that behavioral control reflects value that is both cached (computed and stored during previous experience) and inferred (estimated on the fly on the basis of knowledge of the causal structure of the environment). The latter is thought to depend on the orbitofrontal cortex. Yet some accounts propose that the orbitofrontal cortex contributes to behavior by signaling "economic" value, regardless of the associative basis of the information. We found that the orbitofrontal cortex is critical for both value-based behavior and learning when value must be inferred but not when a cached value is sufficient. The orbitofrontal cortex is thus fundamental for accessing model-based representations of the environment to compute value rather than for signaling value per se.

SUBMITTER: Jones JL

PROVIDER: S-EPMC3592380 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Orbitofrontal cortex supports behavior and learning using inferred but not cached values.

Jones Joshua L JL Esber Guillem R GR McDannald Michael A MA Gruber Aaron J AJ Hernandez Alex A Mirenzi Aaron A Schoenbaum Geoffrey G

Science (New York, N.Y.) 20121101 6109

Computational and learning theory models propose that behavioral control reflects value that is both cached (computed and stored during previous experience) and inferred (estimated on the fly on the basis of knowledge of the causal structure of the environment). The latter is thought to depend on the orbitofrontal cortex. Yet some accounts propose that the orbitofrontal cortex contributes to behavior by signaling "economic" value, regardless of the associative basis of the information. We found ...[more]

PMID: 23162000

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Project description:Recovery from opioid use disorder (OUD) and maintenance of abstinence from opioid use is hampered by perseverant drug cravings that may persist for months after cessation of drug use. Drug cravings can intensify during the abstinence period, a phenomenon referred to as the 'incubation of craving' that has been well-described in preclinical studies. We previously reported that animals that self-administered heroin at a dosage of 0.075 mg/kg/infusion (HH) paired with discrete drug cues displayed robust incubation of heroin craving behavior after 21 days (D) of forced abstinence, an effect that was not observed with a lower dosage (0.03 mg/kg/infusion; HL). Here, we sought to elucidate molecular mechanisms underlying long-term heroin seeking behavior by profiling microRNA (miRNA) pathways in the orbitofrontal cortex (OFC), a brain region that modulates incubation of heroin seeking. miRNAs are small noncoding RNAs with long half-lives that have emerged as critical regulators of drug seeking behavior but their expression in the OFC has not been examined in any drug exposure paradigm. We employed next generation sequencing to detect OFC miRNAs differentially expressed after 21D of forced abstinence between HH and HL animals, and proteomics analysis to elucidate miRNA-dependent translational neuroadaptations. We identified 55 OFC miRNAs associated with incubation of heroin craving, including miR-485-5p, which was significantly downregulated following 21D forced abstinence in HH but not HL animals. We bidirectionally manipulated miR-485-5p in the OFC to demonstrate that miR-485-5p can regulate long-lasting heroin seeking behavior after extended forced abstinence. Proteomics analysis identified 45 proteins selectively regulated in the OFC of HH but not HL animals that underwent 21D forced abstinence, of which 7 were putative miR-485-5p target genes. Thus, the miR-485-5p pathway is dysregulated in animals with a phenotype of persistent heroin craving behavior and OFC miR-485-5p pathways may function to support long-lasting heroin seeking.

Dataset Information

Orbitofrontal cortex supports behavior and learning using inferred but not cached values.

Publications

Orbitofrontal cortex supports behavior and learning using inferred but not cached values.

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