The synaptic basis for social context specific auditory memory formation

社会背景特定听觉记忆形成的突触基础

• 批准号: 10553589
• 负责人: Audrey Ann Mercer
• 金额: $ 7.64万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553589
• 关键词: Acoustic Stimulation; Acute; Adolescent; Adult; Affect; Age; Animals; Architecture; Attention; Auditory; Auditory Evoked Potentials; Behavior; Behavioral; Birds; Brain; Calcium; Cell Nucleus; Cells; Child; Communication; Complex; Cues; Dopamine; Electrophysiology (science); Fellowship; Finches; Genetic; Goals; Human; Human Development; Image; In Vitro; Inhibitory Synapse; Interneurons; Investments; Language; Learning; Link; Mammals; Measurement; Measures; Memory; Mentors; Mentorship; Methods; Midbrain structure; Modeling; Monitor; Motor Cortex; Mus; Neurobiology; Neurons; Output; Parents; Population; Primates; Property; Prosencephalon; Publications; Pupil; Research; Research Personnel; Resolution; Scientist; Siblings; Signal Transduction; Site; Slice; Social Environment; Social Interaction; Songbirds; Speech; Speech Sound; Synapses; Synaptic plasticity; System; Testing; Training; Universities; Viral; Work; balance testing; experience; experimental study; in vivo; in vivo calcium imaging; in vivo imaging; male; optogenetics; patch clamp; peer; relating to nervous system; response; social; sound; tool; tutoring; two-photon; vocal learning; vocalization; zebra finch

PROJECT SUMMARY As children, we learn to speak by listening to the speech of our parents, forming memories of these sounds, and precisely matching our vocal output to these auditory memories. How these auditory memories are formed is not well understood, but auditory memory formation is highly dependent on social context: We learn to selectively copy human speech even if we are raised with other vocal animals. Similarly, juvenile zebra finches learn to sing by first memorizing and then vocally copying the song of an adult zebra finch tutor. Juvenile finches need to know which sounds (i.e., an adult zebra finch’s song; not the song of another bird species) to memorize and copy, which requires a learning mechanism that integrates social context with auditory information. The songbird brain contains a circuit specialized for song learning, making it a tractable system in which to study how social and auditory cues are integrated to form auditory memories. The research proposed here will combine in vitro electrophysiology, optogenetics, and in vivo calcium imaging and behavior to investigate the synaptic basis for the social context-specific formation of the lifelong auditory memories that drive vocal learning in zebra finches. This research will focus on the sensorimotor song region HVC, which is directly involved in tutor song memory formation and which receives social context information via dopamine (DA)-releasing midbrain neurons and tutor song information from auditory cortical inputs. Various lines of evidence lend support to a model in which auditory synapses onto HVC interneurons are a crucial site for encoding tutor song memories. Here I propose to systematically measure the effects of DA on the intrinsic and synaptic properties of identified HVC neurons in vitro, paying particular attention to how DA modulates optogenetically-targeted auditory synapses onto HVC interneurons. I will then use two-photon calcium imaging to measure auditory activity in HVC neurons in juveniles during normal tutoring experience or while pairing DA and tutor song playback, allowing me to directly monitor how auditory memories necessary to vocal learning are stored in the brain. These experiments will be conducted under the mentorship of Dr. Richard Mooney in the Duke University Department of Neurobiology. Dr. Mooney is an experienced mentor with an excellent publication record using a wide variety of cellular, systems, and behavioral approaches to study vocal communication in songbirds and mice. The proposed research will allow me to continue to build on my expertise in electrophysiology from my graduate work, develop expertise in optogenetics and imaging, and continue to progress intellectually as a scientist. In these ways, this fellowship will help me achieve my goal of becoming a successful academic researcher.

项目摘要 作为孩子，我们通过听父母的讲话来学习说话，形成对这些声音的记忆， 并精确地将我们的声音输出与这些听觉记忆相匹配。这些听觉记忆是如何形成的 听觉记忆的形成高度依赖于社会环境：我们学会 选择性地模仿人类的语言，即使我们是和其他发声的动物一起长大的。同样，幼年斑胸草雀 学习唱歌，首先要记住，然后用声音模仿一只成年斑胸草雀导师的歌声。少年 雀类需要知道哪些声音（即，一种成年斑胸草雀的歌声;不是另一种鸟类的歌声）， 记忆和复制，这需要一个学习机制，将社会背景与听觉相结合， 信息.鸣禽的大脑中含有一个专门用于学习歌曲的回路，这使得它成为一个易于处理的系统， 研究社会和听觉线索如何整合形成听觉记忆。研究提出， 这里将结合联合收割机体外电生理学、光遗传学和体内钙成像和行为， 研究终身听觉记忆的社会背景特异性形成的突触基础， 驱动斑胸草雀的发声学习。这项研究将集中在感觉运动歌曲区HVC，这是 直接参与家教歌曲记忆的形成，并通过多巴胺接收社会背景信息 （DA）-释放中脑神经元和家教歌曲信息从听觉皮层输入。各种各样的 证据支持这样一种模型，即HVC中间神经元上的听觉突触是HVC神经元的关键部位。 编码家教歌曲记忆。在这里，我建议系统地测量DA对内在和 突触特性的鉴定HVC神经元在体外，特别注意如何DA调节 HVC中间神经元上的光遗传学靶向听觉突触。我会用双光子钙成像 在正常辅导期间或配对DA时，测量青少年HVC神经元的听觉活动 和辅导歌曲播放，让我直接监测如何听觉记忆必要的声乐学习 都储存在大脑里这些实验将在理查德·穆尼博士的指导下进行， 杜克大学神经生物学系。穆尼博士是一位经验丰富的导师， 出版物记录使用各种各样的细胞，系统，和行为的方法来研究声乐 鸣禽和老鼠的交流。拟议的研究将使我能够继续发展我的 从我的研究生工作电生理学的专业知识，发展光遗传学和成像的专业知识， 作为一名科学家继续在智力上取得进步。在这些方面，这个奖学金将帮助我实现我的目标， 成为一名成功的学术研究者。