In search of the template: the neural substrate of birdsong memory

PROJECT SUMMARY When learning a new motor skill, like playing an instrument or speaking, we benefit from the experience of a mentor. We first memorize our mentor’s actions, forming a template, and then we try to imitate this template memory. Historically, researchers have sought to understand how episodic memories (facts and events) are formed by identifying their neural representations, or engrams, in the hippocampus. In contrast, the neural basis for template memories—the foundation of all imitative learning, remains unknown. Songbirds, like humans, exhibit vocal learning via imitation, as they form an auditory template of their father’s song that guides song learning. Zebra finches have become a popular model to study vocal learning due to their highly stereotyped song and dedicated neural circuit known as the “song system”. Ever since imitative learning was described in songbirds six decades ago, researchers have hunted for the auditory template, as it forms the foundation for learning new motor skills through imitation. Past studies have not yielded clear answers, so I propose a novel strategy to identify the template by investigating its role in song learning. In this framework, I hypothesize the existence of a ‘comparator’ that evaluates vocal output against the template during imitation. This comparison is then used to compute an error signal that guides learning. Recently, my sponsor discovered that dopamine neurons in the ventral tegmental area encodes this error signal. By pioneering dopaminergic fiber photometry in awake, freely moving songbirds, he has enabled easy and chronic access to the key output of the comparator’s evaluation—the error signal—uniquely positioning us to study the neural basis of this comparison. I propose that to identify the template, we first locate the ‘comparator’– the brain region that compares the template to ongoing vocal activity – as the template must be accessed during this comparison. I have identified a candidate comparator within the auditory region known as Avalanche through its connectivity to both the song system and different auditory areas. In Aim 1, I will lesion Avalanche and use dopamine fiber photometry in singing birds to assess its role in computing the error signal. I have already established consistent stereotactic coordinates to target Avalanche and have started recording dopamine in singing birds. In Aim 2, I will use high density electrophysiology to record from Avalanche during error computation to examine how it makes comparisons during song. These experiments will identify a comparator in the brain, making major strides in locating the neural substrate for the template. In addition, avian and mammalian circuits are conserved, so these results could offer insight into neurological disorders in which motor learning is impaired, such as Parkinson’s disease. My research plan will be conducted at Columbia University’s Zuckerman Institute, a highly collaborative environment that supports multidisciplinary projects. Through the guidance of my sponsor, Prof. Vikram Gadagkar, and co- sponsor, Prof. Larry Abbott, I will receive the best training for achieving my goal of conducting neuroscience research as an independent investigator.