The synaptic basis for social context specific auditory memory formation

项目总结 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， 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 但听觉记忆的形成高度依赖于社会背景：我们学习 即使我们是和其他发声动物一起长大的，也要有选择地模仿人类的语言。同样，幼年斑马雀 学习唱歌的方法是先记住一只成年斑马雀导师的歌，然后用声音模仿。少年 雀类需要知道哪种声音(即，成年斑马雀的歌声；而不是另一种鸟类的歌声) 记忆和复制，这需要一种将社会背景与听觉相结合的学习机制 信息。鸣鸟的大脑包含一个专门用于歌曲学习的电路，使其成为一个易于管理的系统 研究社交和听觉线索是如何整合形成听觉记忆的。这项研究建议 这里将结合体外电生理学、光遗传学和体内钙成像和行为来 研究特定于社会背景的终生听觉记忆形成的突触基础 推动斑马雀的发声学习。这项研究将集中在感觉运动歌区HVC，即 直接参与导师歌曲记忆的形成，并通过多巴胺接收社会背景信息 (Da)-从听觉皮质输入释放中脑神经元和辅导歌曲信息。各行各业 证据支持一种模型，在该模型中，与HVC中间神经元的听觉突触是 对辅导歌曲记忆进行编码。在这里，我建议系统地测量DA对内在性和 体外鉴定的HVC神经元的突触特性，特别关注DA是如何调节的 以光基因为靶点的听觉突触连接到HVC中间神经元。然后我会用双光子钙成像 在正常辅导或配对DA时测量青少年HVC神经元的听觉活动 和辅导歌曲播放，让我可以直接监控听觉记忆对声乐学习的必要性 储存在大脑中。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，具有出色的 使用各种细胞、系统和行为方法研究声乐的出版记录 鸣禽和老鼠之间的交流。拟议的研究将使我能够继续在我的 从我的研究生工作中获得的电生理学专业知识，发展光遗传学和成像方面的专业知识，以及 作为一名科学家，继续在智力上取得进步。通过这些方式，这笔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。

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.