Estrogen dependant mechanisms for enhanced social auditory recognition

 描述(申请人提供)：动物的生理状态如何在分子水平上影响社会听觉线索的识别和学习，代表着关于我们的大脑如何偏爱社会信息的知识缺口。动物的生理状态不仅改变了行为反应和后来对同种发声的识别，还调节了听觉皮质的可塑性，增强了行为学习。研究表明，激素，如雌激素(E)，能够促进社交互动，并增强听觉社交线索学习和记忆形成。我们的中心假设是，动物处理和记忆行为相关声音的能力取决于其荷尔蒙状态，荷尔蒙状态反过来会导致在记忆编码时可检测到的分子和行为变化，并增强未来对相同声音的识别。我们通过控制一种主要的母体激素：E.我们将确定E依赖的机制和发声的听觉体验在听觉皮质神经元中诱导了哪些可塑性和记忆相关的分子变化，从而在小鼠发声声音学习的母体模型中研究了这一点。这项拟议的研究具有重要意义，因为它将首次研究建立(目标1)和维持(目标2)记忆的关键分子信号通路是否在依赖经验的交流声音学习过程中在哺乳动物的听觉皮质中受到E的调制。 我们的长期目标是阐明社会听觉学习的神经调节促进作用。揭示E在社会听觉学习中的作用，将加强对我们社会大脑的了解，并找到新的治疗靶点，以改善成人的社会听觉注意和学习。与美国国立卫生研究院的使命一致，针对E下游效应器的治疗靶向有可能改善患者群体的社会听觉注意力和语言学习。

 DESCRIPTION (provided by applicant): How the physiological state of an animal can influence social auditory cue recognition and learning at a molecular level represents a gap in knowledge of how our brains favor social information. The physiological state of an animal not only alters the behavioral response and later recognition of conspecific vocalizations, but also modulates auditory cortex plasticity and enhances behavioral learning. Research indicates that hormones, such as estrogen (E), are capable of facilitating social interactions and enhancing auditory social cue learning and memory formation. Our central hypothesis is that an animal's ability to process and remember behaviorally relevant sounds is dependent on its hormonal state, which in turn enacts molecular and behavioral changes detectable at the time of memory encoding and enhances future recognition of the same sounds. We investigate this in a maternal model of vocalization sound learning in mice by controlling a major maternal hormone: E. We will determine what plasticity and memory associated molecular changes are induced in auditory cortical neurons by E-dependent mechanisms and auditory experience with the vocalizations. The proposed research is significant because it will investigate for the first time whether critical molecular signaling pathways for establishing (Aim 1) and maintaining (Aim 2) memories are modulated by E in the mammalian auditory cortex during experience-dependent, communication sound learning. Our long-term goal is to elucidate the neuromodulatory facilitation of social auditory learning. Exposing E's role in social auditory learning will enhance the understanding of our social brain, and identify new therapeutic targets to improve social auditory attention and learning in adults. In line with the mission of NIH, the therapeutic targeting of downstream effectors of E has the potential to improve social auditory attention and language learning in patient populations.