Dopamine regulation of infant perceptual motor development and communication

Project Summary Healthy development in children relies on social recognition of caregivers and communication of needs, which requires evaluating sensory information and making appropriate and intentional movements. Although this process, referred to as perceptual motor development, is critical for infant social bonding, cognitive development, and lifelong wellbeing, the neuronal basis remains largely unknown. This severe gap in knowledge stems, in part, from the difficulty in manipulating neonate brains and a paucity of robust neonate behaviors as reliable motor outputs in traditional laboratory animals. To address this deficit, this research aims to uncover basic brain mechanisms of neonate social-motor displays using social tadpoles that beg their parents for food by dancing. We combine this novel research organism and behavioral paradigm with advanced neurogenetic tools to interrogate the neuronal substrates of perceptual motor development for infant communication. Recent data from our lab shows that parental recognition is based on olfactory cues, the begging motor display is regulated by dopamine signaling, and the fragile X protein FMRP is enriched specifically in begging neurons. Based on this robust preliminary data, we propose to test the hypothesis that FMRP regulates the dopaminergic signaling required for perceptual motor development. As social recognition is a critical component of infant communication towards caregivers, we will determine how olfactory cues encode caregiver recognition and gate the activity of dopaminergic neurons necessary for begging displays using in vivo imaging and cell ablation experiments. We will also test the role of FMRP in tuning dopaminergic signaling by examining transcriptional changes in dopamine-sensitive cells in FMRP knockout tadpoles compared to wild type animals. Finally, voluntary motor movements likely involve striatal neurons and preliminary suggests begging tadpoles have increased striatal activity. We will functionally test the role of the dopaminergic inputs into the striatum in executing begging behavior and determine how FMRP tunes striatal dopamine signaling. Together, the proposed experiments will systematically dissect the mechanisms by which FMRP and dopamine neurons regulate infant social recognition and communication in a research organism with experimental tractability and a robust social-motor output that is difficult to achieve in other research organisms. As the molecular factors and overall brain organization of social-motor behaviors are conserved across vertebrates, this research will identify generalizable principles of perceptual motor development, a behavior critical for infant survival and life-long wellbeing.