Cellular mechanisms regulating the timing of organizational effects of sex steroid hormones.

Social behavior and the neural circuits that regulate it are organized by sex steroid hormones during critical periods in development (i.e., sexual differentiation). Much is known about how exposure to testosterone and estradiol during the critical period drive lasting changes to the brain. However, relatively little is known about how the timing of critical periods for sexual differentiation is regulated. Given that many parts of the brain (e.g., sensory and cognitive circuitry) are shaped during critical periods, it is not surprising that the regulation of plasticity has been extensively addressed by systems neuroscientists. We advocate that those studying organizational effects of sex steroid hormones should investigate the neural populations, molecules, chemicals, and extracellular matrices that have been found to regulate critical period timing and plasticity in cortical and cognitive circuitry. In particular, we propose that it would be fruitful to investigate how cellular and molecular "brakes" in the preoptic area-hypothalamus and limbic system could stabilize the organizational effects of sex steroid hormones. Here, we provide an overview of organizational effects of sex steroid hormones and of mechanisms underlying the timing of critical periods in sensory and cognitive circuitry, emphasizing how brakes like perineuronal nets could restrict plasticity and cause organizational changes to persist. We also discuss how research on the song system in songbirds serves as an ideal interface between systems neuroscience and behavioral neuroendocrinology and as a powerful opportunity to understand the role of molecular brakes in the organization of social behaviors.