Patterns of neural activity are critical for sculpting the immature brain, and disrupting this activity is believed to underlie neurodevelopmental disorders [1-3]. Neural circuits undergo extensive activity-dependent postnatal structural and functional changes [4-6]. The different forms of neural plasticity [7-9] underlying these changes have been linked to specific patterns of spatiotemporal activity. Since maternal behavior is the mammalian infant's major source of sensory-driven environmental stimulation and the quality of this care can dramatically affect neurobehavioral development [10], we explored, for the first time, whether infant cortical activity is influenced directly by interactions with the mother within the natural nest environment. We recorded spontaneous neocortical local field potentials in freely behaving infant rats during natural interactions with their mother on postnatal days ∼12-19. We showed that maternal absence from the nest increased cortical desynchrony. Further isolating the pup by removing littermates induced further desynchronization. The mother's return to the nest reduced this desynchrony, and nipple attachment induced a further reduction but increased slow-wave activity. However, maternal simulation of pups (e.g., grooming and milk ejection) consistently produced rapid, transient cortical desynchrony. The magnitude of these maternal effects decreased with age. Finally, systemic blockade of noradrenergic beta receptors led to reduced maternal regulation of infant cortical activity. Our results demonstrate that during early development, mother-infant interactions can immediately affect infant brain activity, in part via a noradrenergic mechanism, suggesting a powerful influence of the maternal behavior and presence on circuit development.