Neuronal circuit mechanisms for learning during social interactions

 描述(由应聘者提供)：即使是短暂的社交互动也能产生持久的记忆，并深刻地塑造未来的行为。例如，言语、语言和其他文化传播的行为都是从社会经验中学习的。解决大脑如何形成并保持对社会经验的长期记忆是神经科学的一个重要目标，因为它可以为我们如何相互学习和如何沟通提供基本的见解。除了人类的言语和语言学习，鸟类的歌唱学习提供了一个最明显的例子。只需一只成年鸟的短暂辅导，一只幼年鸣鸟就会建立起对成年模特歌曲的准确而持久的记忆，这一点从几周后，以及在某些物种，几个月和几年后对这首歌的精确发声模仿就可以证明。识别编码和保留这些持久表征的神经元回路的一个主要挑战是，我们无法远程监控和操纵与社会互动和学习一致的时间尺度上的神经元活动。使用条件靶向神经元的光遗传操作、语音识别软件和神经元活动的光学成像，我们已经克服了这些方法障碍。这项研究将通过辅导、视遗传抑制和幼鸟神经元活动的双光子成像来识别编码和存储发声模仿所需的导师歌曲记忆的特定神经元。有几条证据表明，歌曲运动前核团HVC与导师的歌曲记忆有关。然而，目前还不清楚HVC或HVC下游的一类神经元，包括听觉前脑中的神经元，是否具有编码这种记忆的功能。这项建议的目的是通过识别编码导师歌曲记忆的特定一类或几类神经元，揭示它在青少年大脑中的功能表现，并研究歌曲记忆如何与评估歌唱表现的重要回路相互作用来解决这个问题。在这项建议的第一个目标中，我们将使用抑制性光敏通道的条件表达来暂时沉默这些大脑区域中不同类别的神经元，以测试它们在辅导歌曲学习中的必要性。 在第二个目标中，我们将使用神经活动的活体成像来检查导师歌曲的感觉体验是如何在大脑中功能和空间上呈现的。在第三节 目的我们将在发声排练过程中使用光遗传抑制来确定编码导师歌曲记忆的神经元如何与听觉反馈电路相互作用。通过这些目标，我们将提供关于大脑如何编码和保留声乐模型的记忆以及这些记忆如何塑造未来行为的基本见解。

 DESCRIPTION (provided by applicant): Even brief social interactions can lead to long lasting memories that profoundly shape future behavior. For example, speech, language, and other culturally transmitted behaviors are learned from social experiences. Resolving how the brain forms and retains long-lasting memories of social experiences is an important goal in neuroscience because it can provide fundamental insights into how we learn from one another and how we communicate. Aside from human speech and language learning, song learning in birds provides one of the clearest examples of this. Following only brief tutoring from an adult bird, a juvenile songbird will establish an accurate, long-lasting memory of the adult model's song, as evidenced by the precise vocal imitation of this song many weeks, and in some species, months and years, later. A major challenge to identifying the neuronal circuits that encode and retain these lasting representations has been our inability to remotely monitor and manipulate neuronal activity on time scales congruent with social interactions and learning. Using optogenetic manipulation of conditionally targeted neurons, voice recognition software and optical imaging of neuronal activity, we have overcome these methodological road blocks. This research will identify the specific neurons that encode and store the memory of the tutor's song needed for vocal imitation using tutoring contingent optogenetic inhibition and two-photon imaging of neuronal activity in juvenile birds. Several lines of evidence have implicated the song premotor nucleus HVC in tutor song memory. However, it is not clear whether a single class of neurons in HVC or downstream of HVC, including those in the auditory forebrain, function to encode this memory. The objective of this proposal is to resolve this issue by identifying the specific class or classes of neurons that encode the tutor song memory, revealing how it is functionally represented in the juvenile brain, and examining how the song memory interacts with circuits important for evaluating singing performance. In the first aim of this proposal we wil use the conditional expression of an inhibitory light sensitive channel to transiently silence different classes of neurons in these brain regions to test their necessity in tutor song learning. In the second aim we will use in vivo imaging of neuronal activity to examine how sensory experience of the tutor's song is functionally and spatially represented in the brain. In the third aim we will use optogenetic inhibition during vocal rehearsal to identify how neurons encoding the tutor song memory interact with auditory feedback circuits. Through these aims we will provide fundamental insights into how the brain encodes and retains memories of vocal models and how these memories shape future behaviors.