Social Dominance Reorganizes the Transcriptomic Neuropeptidome in a Highly Social Cichlid Fish

Abstract

Complex behavioral phenotypes, such as social status, emerge from the genome across biological levels, with many of the fundamental neural mechanisms shared across vertebrates. While various aspects of the brain have been implicated in modulating social behavior, critical regulators include cells of the preoptic area (POA) and hypothalamus, which by applying cellular-resolution transcriptomic approaches allows for greater exploration of cellular dynamics in these cells. Yet, how complex gene networks function between and within cell types to regulate complex social behavior is still poorly understood. Importantly, when considering functionally relevant neuronal classes of genes such as neuropeptides, understanding the inherent complexity that emerges from the interaction of these genes in the transcriptomic neuropeptidome can provide unique insight into how social behavior is regulated. Here, we used single-nucleus RNA-sequencing in the hypothalamus and POA of a highly social cichlid fish, Astatotilapia burtoni, to understand the effect that social status has on cellular-level transcriptomic profiles. Males of this species are well known for their highly plastic phenotypes related to social status, which allows for a hypothesis-driven approach. We demonstrate how social status manifests in changes of gene co-expression networks across neuronal populations and highlight transcriptomic signatures of social dominance when targeting known functional differences among AVP neuronal cell types. We implement a novel approach to relate how differences in social state translate to the integration of the transcriptomic neuropeptidome. Taken together, this research provides insights into how gene expression networks that modulate social behavior, including neuropeptide networks, function at the cellular level.