The long-term goal of the proposed project is to understand how steroid hormones modify the functional properties of neurons and neuronal circuits to produce sexually distinct behavior patterns. In this project, the link between steroid hormones, neuronal function, and behavior will be investigated by using the vocal behavior of the African clawed frog as a model. Male and female frogs produce sexually distinct vocalizations that are regulated by steroid hormones. The vocalizations of male and female Xenopus are produced by the sex-specific firing rates of laryngeal motoneurons that control the vocal organ. Thus, in this system, the challenge of understanding the neural mechanisms of behavior can be reduced to a problem of understanding generation of stereotyped rhythmic spike patterns by motoneurons. The proposed research will investigate how biophysical and structural properties of laryngeal motoneurons and premotor neurons are modified by steroid hormones, and how these changes help shape the motor output that underlies sex-specific vocal production. Ultimately, understanding how steroids modulate the excitability of neurons will be important in unraveling the mechanisms of numerous human diseases including such common and important problems as epilepsy. Recent data suggests that certain steroids may be used as anti-epileptic drugs while in some patients, steroid hormones clearly increase the incidence of epileptic seizure. In addition, seizures can be linked to the menstrual cycle. However, there is very little known about how steroids can induce a sudden synchronous firing among neurons that causes seizure nor how they can be used to prevent such a storm of activity. By studying a well-defined neural system in which neuronal excitability is clearly regulated by androgen, as proposed here, we can better understand the cellular mechanisms that trigger bursts of neuronal activity. This more detailed understanding of cellular activity is necessary for further progress to be made in developing therapeutic approaches to epilepsy.
