Estrogen dependant mechanisms for enhanced social auditory recognition

增强社会听觉识别的雌激素依赖性机制

• 批准号: 9124372
• 负责人: Amielle Moreno
• 金额: $ 4.36万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9124372
• 关键词: Acoustics; Address; Adult; Affect; Animals; Attention; Auditory; Auditory area; Autistic Disorder; Behavior; Behavioral; Birth; Brain; Caring; Cochlear Implants; Communication; Cues; Disease; Electrophysiology (science); Environment; Epigenetic Process; Estrogens; Female; Future; Genetic Transcription; Goals; Hearing; Histone Acetylation; Hormonal; Hormones; Human; Individual; Knowledge; Language Development; Lead; Learning; Longevity; Maintenance; Measures; Memory; Mission; Modeling; Modification; Molecular; Mothers; Mus; Neuromodulator; Neurons; Patients; Physiological; Process; Proteins; Research; Role; Schizophrenia; Shapes; Signal Pathway; Signal Transduction; Site; Social Facilitation; Social Interaction; Stimulus; Time; Ultrasonics; United States National Institutes of Health; Work; auditory stimulus; autism spectrum disorder; base; behavioral response; experience; improved; improved outcome; information processing; interest; long term memory; memory encoding; molecular recognition; neuroregulation; neurotropic; new therapeutic target; patient population; public health relevance; pup; response; sensory cortex; social; social learning; sound; therapeutic target; therapy design; vocalization

 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.

 描述（由申请人提供）：动物的生理状态如何在分子水平上影响社会听觉线索识别和学习，这代表了我们的大脑如何偏好社会信息的知识空白。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，而且还调节了听觉皮层的可塑性并增强了行为学习。研究表明，激素，如雌激素（E），能够促进社会互动，增强听觉社会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激素状态，这反过来又会在记忆编码时产生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。我们在小鼠发声声音学习的母体模型中通过控制一种主要的母体激素：E。我们将确定什么样的可塑性和记忆相关的分子变化，诱导听觉皮层神经元的E依赖机制和听觉经验的发声。这项研究意义重大，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经验依赖的交流声音学习过程中被哺乳动物听觉皮层中的E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增强对我们社会大脑的理解，并确定新的治疗靶点，以改善成年人的社会听觉注意力和学习。与NIH的使命一致，E下游效应物的治疗靶向具有改善患者群体的社会听觉注意力和语言学习的潜力。