The synaptic basis for social context specific auditory memory formation

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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.