Neuronal and genetic imprints of male mating experience

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PROJECT SUMMARY Understanding the mechanisms and behavioral relevance of synaptic plasticity has been an active area of research for decades. However, how neural plasticity modulates innate behaviors, such as mating behaviors, is largely unexplored. In addition, cellular and molecular mechanisms of presynaptic neural circuit plasticity remain elusive. Both knowledge gaps will be addressed in this proposal, which focuses on the mechanisms of presynaptic plasticity of a hypothalamic circuit that governs male sexual behavior. Male mice improve in their mating performance after sexual experience, but the underlying neural circuit mechanisms are poorly understood. We observed a dramatic increase of presynaptic axonal termini in the projection from bed nucleus of stria terminalis (BNST) neurons expressing tachykinin 1 (BNSTTac1) to preoptic hypothalamus (POA), a circuit that is essential for male mating behavior. We hypothesize that this structural plasticity in BNSTTac1àPOA projections is critical for the enhancement of mating behavior following sexual experience. We will first characterize the cellular (presynaptic bouton dynamics) and electrophysiological (synaptic transmission efficacy) mechanisms of this plasticity with chronic in vivo imaging and slice recording. Further, we aim to dissect the molecular pathways underlying this plasticity with deep RNA sequencing and genetic manipulations. Lastly, we will perform behavioral tests to study how this plasticity modulates the display of male sexual behaviors. Our results will uncover the specific mechanisms modulating a key brain circuit for controlling mating behavior, which may inspire potential therapeutic approaches to alleviate low libido in humans.