Project Summary Steroid hormones enrich behavior through actions on sensory and motor circuits, but it remains unclear how these parallel actions are coordinated to generate a coherent behavioral phenotype. This proposal will investigate the effects of steroids on neurons that convey predictive motor signals, termed corollary discharges (CD), which modify sensory processing to account for the sensory feedback predicted to arise from an animal’s own actions, termed reafference. CDs are ubiquitous in sensorimotor systems, and their disruption is thought to underlie some behavioral and sensory deficits in psychiatric conditions including schizophrenia and autism. Hormonal regulation of CD is especially intriguing given that steroid hormone levels also appear to be dysregulated in these conditions. However, the mechanisms by which steroids regulate CD circuitry in nonpathological states remain unknown. The central hypothesis of this proposal is that steroid hormones directly alter the physiology of corollary discharge neurons to match internal motor representations to altered reafferent feedback. This hypothesis will be tested using a well-characterized CD that modulates sensory processing in mormyrid electric fish. Mormyrids communicate using a stereotyped electric pulse known as an electric organ discharge (EOD). Self- generated EODs and EODs of nearby fish activate electroreceptors in the skin, which project to a dedicated communication pathway. To ensure that this pathway only responds to EODs of other fish, a CD signals the timing of EOD production to selectively inhibit responses to self-generated EODs. EODs are elongated in response to increases in testosterone (T) levels in male mormyrids during the breeding season. This T-induced EOD elongation delays electroreceptor activation, shifting the timing of reafferent sensory feedback. To match these shifts in sensory feedback, T concurrently acts in the brain to delay and elongate CD inhibition. Preliminary data from extracellular recordings reveal the locus in the CD pathway whereby activity is delayed and elongated by T. Importantly, the hormonal pathways and physiological mechanisms underlying timing shifts at this site are still unknown. The experiments in Aim 1 will identify the steroid receptors that drive CD plasticity and determine whether these receptors act directly in CD neurons. The experiments in Aim 2 will reveal the physiological mechanisms by which T shifts CD timing in affected neurons. By focusing on a hormone-sensitive circuit that conveys a simple internal model, the timing of EOD production, these investigations will yield mechanistic insight into the seasonal effects of steroid hormones on gene expression and neural excitability in the context of a quantifiable behavioral change. Further, the results of these experiments promise to offer insight into the neural basis of multiple psychiatric conditions in which steroid hormone levels and CD appear to be dysregulated. With the...