Interdisciplinary Initiatives Program Round 5 – 2010

Juan Santiago, Mechanical Engineering
Robert Sapolsky, Neurology & Neurological Sciences   
Helen Blau, Microbiology & Immunology

Oxytocin is a potent hormone involved in many human experiences including maternal bonding to infants, and human mothers with low oxytocin release in response to infant cues such as smiling and crying are less attentive to their infants. Oxytocin is being tested as a treatment for autism and social phobia, and thus oxytocin-based treatment options for low-oxytocin mothers may soon be available, however excess oxytocin causes side-effects including desensitization and impaired memory in humans and mice, the latter mediated by stress hormones. Conversely, delivery of oxytocin during viewing of faces enhances memory of those faces. Thus timing of oxytocin signaling is critical: It has memory-impairing effects after a stressful event, and memory-enhancing effects during a social event. Thus, the evidence suggests that the benefits of oxytocin supplementation can be maximized, and the negative learning and memory side effects minimized, with oxytocin delivery during relevant behaviors and events. Specifically, since oxytocin is released in human mothers exposed to infant cues, and oxytocindeficient mice lack mothering behavior, we hypothesize that delivering oxytocin to oxytocin-deficient mice in synchrony with pup ultrasonic vocalizations will restore mothering behavior and prevent the negative side effects on learning and memory of stressful cues, as compared to flat-rate delivery or saline control. We will test this hypothesis using a new mouse-implantable remote-control system for behavior-based drug delivery which we recently developed.

If successful, this research will provide motivation for clinical studies to test delivery of oxytocin to low-oxytocin human mothers exclusively during interactions with their infants to enhance maternal bonding while minimizing side effects, and validate our novel behavior-based drug delivery system as a valuable tool for a broad range of biomedical applications.