Impaired experience-dependent maternal care in presynaptic active zone protein CAST-deficient dams

Although sociological studies affirm the importance of parental care in the survival of offspring, maltreatment-including child neglect-remains prevalent in many countries. While child neglect is well known to affect child development, the causes of maternal neglect are poorly understood. Here, we found that female mice with a deletion mutation of CAST (a presynaptic release-machinery protein) showed significantly reduced weaning rate when primiparous and a recovered rate when multiparous. Indeed, when nurturing, primiparous and nulliparous CAST knock out (KO) mice exhibited less crouching time than control mice and moved greater distances. Contrary to expectations, plasma oxytocin (OXT) was not significantly reduced in CAST KO mice even though terminals of magnocellular neurons in the posterior pituitary expressed CAST. We further found that compared with control mice, CAST KO mice drank significantly less water when nurturing and had a greater preference for sucrose during pregnancy. We suggest that deficiency in presynaptic release-machinery protein impairs the facilitation of some maternal behaviours, which can be compensated for by experience and learning.