Social Status-dependent regulation of an identified brain circuit

East Carolina University, Greenville NC

Investigators

Abstract

Social hierarchies are organizing agents for all social animals. They allow the peaceful yet unequal division of natural resources based on the dominance rank of group members. As social hierarchies mature, animals begin to alter their behavior according to their social rank. This project advances understanding of the neural mechanisms that underlie social aggression and how social experience shapes animal behavior based on social rank. Using zebrafish as a model organism and an integrative approach of behavioral, cellular, including electrophysiological, and molecular analysis, the investigators study how social experience regulates identified brain centers involved in modulation of behavioral output according to their social rank. Specifically, investigators study how social status is encoded in brain and the mechanisms through which it regulates the startle escape response. Zebrafish are an ideal model organism to address these key questions because they are highly social animals and form stable dominant-subordinate relationships that can readily be investigated. Moreover, zebrafish can be modified genetically to pinpoint specific pathways that control specific motor responses. Results from this project will provide a better understanding of the neural mechanisms underlying social aggression and how social information is encoded within the brain to alter motor activity. In addition, the project provides extensive research experiences for undergraduate students from diverse backgrounds, as well as includes science educational activities for middle and high school students. This project investigates the interplay between hypothalamic dopaminergic nuclei and their modulation of the Mauthner neural circuit that underlies escape responses in zebrafish. The Mauthner neurons are a single pair of reticulospinal neurons activated by auditory stimuli and innervate contralateral spinal motor neurons. Supra-threshold stimuli activate the Mauthner neurons and leads to the startle response. The startle response is also prone to descending dopaminergic (DA) modulatory input from the hypothalamus. Building on evidence that DA plays an important role in social aggression, motivation, and stress, this project investigates the mechanisms by which DA controls escape behavior in animals of different social status. To this end, a combination of molecular, electrophysiological and calcium imaging, histological, genetic, pharmacological, and behavioral approaches are utilized. Additionally, the project examines the role of nuclear progestin receptor in regulating dopaminergic activity. Hypothalamic DA neurons express the nuclear progestin receptor (Pgr), a transcriptional factor that regulates expression of target genes involved in hormonal regulation. Prompted by preliminary data indicating a regulatory role of Pgr on DA pathways, experiments are undertaken to elucidate the underlying neural and hormonal signals that determine social regulation of the descending dopaminergic input to the Mauthner escape circuit. Collectively, the studies will advance understanding of the mechanisms that underlie modulation of behavior by social information. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.