Dataset Information

Interactions between human orbitofrontal cortex and hippocampus support model-based inference.

ABSTRACT: Internal representations of relationships between events in the external world can be utilized to infer outcomes when direct experience is lacking. This process is thought to involve the orbitofrontal cortex (OFC) and hippocampus (HPC), but there is little evidence regarding the relative role of these areas and their interactions in inference. Here, we used a sensory preconditioning task and pattern-based neuroimaging to study this question. We found that associations among value-neutral cues were acquired in both regions during preconditioning but that value-related information was only represented in the OFC at the time of the probe test. Importantly, inference was accompanied by representations of associated cues and inferred outcomes in the OFC, as well as by increased HPC-OFC connectivity. These findings suggest that the OFC and HPC represent only partially overlapping information and that interactions between the two regions support model-based inference.

SUBMITTER: Wang F

PROVIDER: S-EPMC6974031 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Interactions between human orbitofrontal cortex and hippocampus support model-based inference.

Wang Fang F Schoenbaum Geoffrey G Kahnt Thorsten T

PLoS biology 20200121 1

Internal representations of relationships between events in the external world can be utilized to infer outcomes when direct experience is lacking. This process is thought to involve the orbitofrontal cortex (OFC) and hippocampus (HPC), but there is little evidence regarding the relative role of these areas and their interactions in inference. Here, we used a sensory preconditioning task and pattern-based neuroimaging to study this question. We found that associations among value-neutral cues we ...[more]

PMID: 31961854

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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.

Project description:Shared neuronal variability has been shown to modulate cognitive processing. However, the relationship between shared variability and behavioral performance is heterogeneous and complex in frontal areas such as the orbitofrontal cortex (OFC). Mounting evidence shows that single-units in OFC encode a detailed cognitive map of task-space events, but the existence of a robust neuronal ensemble coding for the predictability of choice outcome is less established. Here, we hypothesize that the coding of foreseeable outcomes is potentially unclear from the analysis of units activity and their pairwise correlations. However, this code might be established more conclusively when higher-order neuronal interactions are mapped to the choice outcome. As a case study, we investigated the trial-to-trial shared variability of neuronal ensemble activity during a two-choice interval-discrimination task in rodent OFC, specifically designed such that a lose-switch strategy is optimal by repeating the rewarded stimulus in the upcoming trial. Results show that correlations among triplets are higher during correct choices with respect to incorrect ones, and that this is sustained during the entire trial. This effect is not observed for pairwise nor for higher than third-order correlations. This scenario is compatible with constellations of up to three interacting units assembled during trials in which the task is performed correctly. More interestingly, a state-space spanned by such constellations shows that only correct outcome states that can be successfully predicted are robust over 100 trials of the task, and thus they can be accurately decoded. However, both incorrect and unpredictable outcome representations were unstable and thus non-decodeable, due to spurious negative correlations. Our results suggest that predictability of successful outcomes, and hence the optimal behavioral strategy, can be mapped out in OFC ensemble states reliable over trials of the task, and revealed by sufficiency complex neuronal interactions.

Dataset Information

Interactions between human orbitofrontal cortex and hippocampus support model-based inference.

Publications

Interactions between human orbitofrontal cortex and hippocampus support model-based inference.

Similar Datasets

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