Catecholamine systems, which include dopamine and noradrenaline, are fundamental to the processes of social incentive and reward, but relevant studies have focused almost exclusively on the mesolimbic dopamine system, which influences behavioral responses to highly processed representations of environmental stimuli However, catecholamine projections are also observed to sensory areas of the brainstem and even to the auditory periphery, suggesting that social incentive processes may begin with the modulation of responsiveness in the auditory periphery and primary sensory areas of the brain. Most studies that have investigated steroid regulation of tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis, have focused on long term effects of estrogen replacement on the mesocorticolimbic dopaminergic system, but not in primary sensory processing areas. The objective of this proposal is to discover how steroid hormones interact with catecholamines in circuits important for normal auditory-driven social behavioral interactions. By employing a simple but powerful vertebrate model system in a robust behavioral experiment that involves an unambiguous response to a social auditory stimulus, the activation of specific brain nuclei with homologous neurochemical contents and connections to mammals and humans will be analyzed. Furthermore, by experimental manipulation of circulating steroid hormones, a better understanding will be gained of how steroids, such as estrogen, regulate catecholamines within peripheral, primary and secondary auditory processing centers. The contribution of the proposed research is expected to provide a greater understanding of the involvement of catecholaminergic neurons during behavioral response to social auditory signals, and the mechanisms of chronic and acute steroid regulation of catecholamines in the central and peripheral auditory system. This contribution will be significant because it will become the foundation for future research that will provide insight to the role of catecholamines and their regulation by steroids in brain circuits required for normal social function. The proposed project is innovative, in our opinion, because it employs a simple vertebrate model system and has the advantage of measuring an unambiguous behavioral response to an important social auditory stimulus that is not tenable in mammalian models.
These findings will help delineate important, highly conserved neurochemicals, and their regulation by steroid hormones, in brain circuitry necessary for proper auditory-driven social function. This may be especially relevant to human disorders such as Asperger's syndrome and autism, which are characterized by poor orientation to social vocalizations.
