PROJECT SUMMARY Vocalization (i.e., cry) is the first and most intense behavior manifestation in the life of a neonate. Neonates vocalize when isolated from their primary caregivers, attracting their attention to receive comfort, care, and nutrition. In humans, atypical cry behavior is symptomatic of neurodevelopmental disorders, such as autism and Angelman syndrome. However, how the immature neonatal brain controls vocal behavior is a fascinating question in developmental neurobiology that remains unsolved. The goal of this proposal is to elucidate neural circuits that transiently modulate the emission of vocalizations in neonatal mammals. The hypothalamus is a region in the bottom of the mammalian brain suggested to mediate vocalization based on experiments using electric stimulation of this brain region. In the hypothalamus, there is a region called the arcuate nucleus, which contains two populations of neurons that produce either Agouti-related peptide (Agrp) or Proopiomelanocortin (POMC). Our preliminary experiments suggest these two populations of neurons exert a modulatory role in the emission of neonatal vocalizations. Thus, in this proposal, we will use state-of-the-art approaches in circuit neurosciences applied to the neonatal brain to investigate the mechanistic details involved in the control of neonatal vocal behavior by Agrp and POMC neurons. At its conclusion, this project will reveal novel neuronal circuits that control precise behavior outputs in the developing mammalian brain. This project will also shed new light on how vocal behavior dynamically changes during early postnatal life. In addition to illuminating fundamental principles of behavior control early in life, the mechanistic insights revealed in this project might also aid the understanding of impaired vocal behavior in several neurodevelopmental diseases.