ABSTRACT Human parents and non-parents show sharply distinct patterns of brain activity in response to infant cries or laughter. How is this change in brain responses accomplished? Receiving parental care is essential for appropriate physical, cognitive, and emotional development in infants. Failure to care for an infant predisposes the individual to neurodevelopmental and psychiatric disorders. Caregiving behavior is mediated by neural circuits that promote bonding with infants. Past research has primarily focused on neural mechanisms in mothers associated with pregnancy, parturition, and lactation that facilitate parenting. However, many species show bi-parental care, suggesting that additional mechanisms drive infant care in males. Recent studies have identified neural circuits involved in pro- and anti-parental behavior in both males and females. In this proposal, we aim to leverage our knowledge about these molecularly defined circuits involved in pro- and anti- parental behavior in mice to reveal how hypothalamic circuits nodes directly interact to coordinate infant- directed behavior across behavioral states. How does circuit activity in molecularly defined populations correlate with infant-directed behavior? In Aim 1, we will address this question by determining the relationship of two molecularly defined circuit nodes critical for infant-directed behavior using in vivo fiber photometry and chemogenetic manipulations. What synaptic mechanisms underlie observed behaviorally relevant circuit activity? In Aim 2, we will address this question using electrophysiological (whole cell recording with optogenetic or pharmacological manipulations) techniques to dissect cell intrinsic and plasticity mechanisms within this molecularly defined microcircuit in behaviorally phenotyped animals. These experiments are designed to disentangle intrinsic mechanisms and plasticity induced by synaptic or neuropeptidergic effects across behavioral states in both sexes. What molecules underlie behaviorally relevant circuit and synaptic mechanisms? In Aim 3, we will address this question using translating ribosome affinity purification followed by RNASeq to identify candidate genes for specific mechanisms underlying behavioral, circuit, and synaptic effects. These genes will be validated by in situ hybridization. Together, these experiments will uncover the common or dissociable neural circuit mechanisms underlying adaptive infant-directed behavior across sexes and behavioral states and provide the initial electrophysiological characterization of this neuropeptidergic hypothalamic microcircuitry. With the increased recognition of a dedicated circuit for negative infant-directed behavior, it is critical to have a mechanistic understanding of the neurobiological and physiological interactions among circuitry underlying pro- and anti-parental behaviors. Understanding the mechanisms for caregiving allows us to identify key entry points for intervention to support healt...