Although there is obvious variation in brain organization across vertebrate species, the basic brain blueprint has remained remarkably stable for millions of years, as have the mechanistic principles associated with how it regulates various functions, including behavior. That conservation includes the presence of common circuits across vertebrates that are critical for social regulation. In my lab, we explore the molecular, cellular, and behavioral mechanisms through which two types of molecules, sex steroids and neuropeptides in the vasopressin/oxytocin family, act within those circuits to influence social behaviors associated with reproduction.
Non-genomic Sex Steroid Mechanisms and Social RegulationImmunohistochemical labeling of GPR30, a membrane estrogen receptor (red) and the peptide isotocin (green) showing that the same cells in the preoptic area make both molecules.
We know a great deal about the genomic mechanisms through which androgens and estrogens influence behavior; by turning genes on and off and thus affecting levels of proteins in cells, they slowly sculpt the brain circuits and peripheral structures required to produce social output. However, we now recognize that steroids can also rapidly modulate how those circuits respond to social stimuli by acting on receptors on neuronal membranes, a non-genomic mechanism. Steroids thus play dynamic roles in social regulation. We are currently trying to identify the membrane receptors that mediate rapid effects of androgens and estrogens on behavioral and physiological processes related to courtship in goldfish, as well as to determine if these steroids rapidly affect early stages of sensory processing in ways that amplify neural responses to social stimuli. We are also beginning to explore if sex steroids have similar, rapid effects in closely related zebrafish. If so, we will be able to take advantage of the genetic tools developed in that species to increase the resolution with which we can examine non-genomic steroid mechanisms.
Nonapeptides and Socialiality
In vertebrates, 9-amino acid containing peptides in the vasopressin/oxytocin family all evolved from a common ancestral molecule, vasotocin, in which a gene mutation gave rise to the mammalian homologue, vasopressin. Gene duplications and subsequent mutations also led to the evolution of numerous sister nonapeptides across vertebrates, including isotocin in teleost fish and oxytocin in mammals. All are structurally similar, produced in the brain, and play important roles in social regulation across vertebrates, though they can influence behavior differently depending on the species, sex and social context. In reproductive contexts in male goldfish, vasotocin inhibits approach responses towards other males, but not towards ovulating females. We have characterized the circuit that mediates its ability to promote social withdrawal, and we are now exploring the mechanisms that turn that circuit off when males interact with females. Specifically, we are exploring the possibility that unique social cues differentially regulate expression of the gene for the vasotocin receptor and/or for related proteins that may dimerize with the receptor and thus modulate its binding and/or cell signaling properties, either of which could change the peptide’s behavioral effects across social contexts.
We are also exploring how intranasal vasopressin, which crosses the blood brain barrier in humans, influences subjective responses to faces in men and women and, through a collaboration with James Rilling at Emory University, how vasopressin modulates brain responses to those stimuli. These studies have indicated that, as in other vertebrates, vasopressin’s social effects in humans are sex-specific and differ as a function of social context. They have also suggested that a single, intranasal dose of vasopressin may produce lasting effects on some social responses.