Investigating Orbitofrontal Circuit Mechanisms of Social Rank and Dominance Behavior

NIH RePORTER · NIH · K00 · $5,541 · view on reporter.nih.gov ↗

Abstract

Throughout the animal kingdom, social species establish social hierarchies and use social rank to guide the appropriate expression of dominance behaviors that are critical for survival. Neurobiological investigations have identified a key role for medial prefrontal cortex to lateral hypothalamus projection circuits in representing social ranks and mediating the expression of social dominance behaviors. The orbitofrontal cortex (OFC) has also been shown to process social information. OFC processes are thought to be mediated by vast neuromodulatory innervation from subcortical structures known to regulate sociability, such as the dorsal raphe nucleus (DRN). Serotonergic (5-HT) DRN neurons have been identified as a key neural substrate for mediating social interaction behaviors and they provide the majority of serotonergic innervation to the OFC. However, it is unclear whether DRN5-HT-OFC circuits can process social ranking information to influence behaviors dictated by social ranks. Our research proposal aims to characterize the largely unexplored role of OFC in representing social ranks as well as reveal for the first time whether OFC interactions with serotonergic systems regulate the expression of social dominance behaviors during social competition. The central hypothesis of this project is that OFC encodes social ranking information during social competition and that serotonergic input from DRN modulates the expression of dominance behaviors. To test this, this research will use machine learning tools to automatically track and classify social competition behaviors in multiple animals. This research will then characterize behavioral states that are encoded by OFC neurons by measuring population dynamics aligned to classified social competition behaviors. Finally, experiments in this project will activate DRN5-HT-OFC projection terminals and establish how manipulating serotonergic circuit activity changes the expression of social dominance behaviors during social competition. Project findings will establish a novel, circuit-specific mechanism for how the brain processes social ranking information to adjust behavior accordingly during social competition. Developing a better understanding of the neuronal mechanisms governing the appropriate expression of social behaviors will provide great value to clinicians and translational researchers wanting to treat social behavior control deficits observed in psychiatric disease. Execution of this proposal will be made possible by the Tye lab’s expertise in social behaviors and neural circuit dissection as well by expanding upon candidate’s prior training in calcium imaging, optogenetics, and computational analysis.

Key facts

NIH application ID
10670442
Project number
5K00MH132569-04
Recipient
SALK INSTITUTE FOR BIOLOGICAL STUDIES
Principal Investigator
Christian Cazares
Activity code
K00
Funding institute
NIH
Fiscal year
2023
Award amount
$5,541
Award type
5
Project period
2020-12-03 → 2023-08-31