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Next-generation sequencing of anterior cingulate cortex neurons in a social problem setting in rats

ABSTRACT: We studied the brain mechanisms of ‘social problem’ where a worker’s credit is exploited in a group setting. A stable ‘worker-parasite’ relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the ‘worker,’ engaged in lever-pressing while the other ‘parasitic’ rats profited by crowding the feeder in anticipation. c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. ACC inactivation suppressed the worker’s lever-press behavior under the social dilemma settings. Importantly, our RNA sequencing and the differential expression analysis showed that GABA- and potassium channel-related mRNA expressions decreased in the worker’s ACC. In contrast, network disinhibition induced-activity responsive genes such as Cyr61, Arc, and Klf are upregulated. These results suggest that downregulation and upregulation of network inhibitory and excitatory factors, respectively, in the ACC of the worker compared to parasite rats.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE153649 | GEO | 2021/11/12

REPOSITORIES: GEO

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Project description:BACKGROUND: Social insects, such as honey bees, use molecular, physiological and behavioral responses to combat pathogens and parasites. The honey bee genome contains all of the canonical insect immune response pathways, and several studies have demonstrated that pathogens can activate expression of immune effectors. Honey bees also use behavioral responses, termed social immunity, to collectively defend their hives from pathogens and parasites. These responses include hygienic behavior (where workers remove diseased brood) and allo-grooming (where workers remove ectoparasites from nestmates). We have previously demonstrated that immunostimulation causes changes in the cuticular hydrocarbon profiles of workers, which results in altered worker-worker social interactions. Thus, cuticular hydrocarbons may enable workers to identify sick nestmates, and adjust their behavior in response. Here, we test the specificity of behavioral, chemical and genomic responses to immunostimulation by challenging workers with a panel of different immune stimulants (saline, Sephadex beads and Gram-negative bacteria E. coli). RESULTS: While only bacteria-injected bees elicited altered behavioral responses from healthy nestmates compared to controls, all treatments resulted in significant changes in cuticular hydrocarbon profiles. Immunostimulation caused significant changes in expression of hundreds of genes, the majority of which have not been identified as members of the canonical immune response pathways. Furthermore, several new candidate genes that may play a role in cuticular hydrocarbon biosynthesis were identified. Finally, we identified common genes regulated by pathogen challenge in honey bees and other insects, suggesting that immune responses are conserved at the molecular level. CONCLUSIONS: These studies suggest that honey bee genomic responses to immunostimulation are substantially broader than expected, and may mediate the behavioral changes associated with social immunity by orchestrating changes in chemical signaling.

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Next-generation sequencing of anterior cingulate cortex neurons in a social problem setting in rats

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