NMDA receptor activity in utero averts respiratory depression and anomalous long-term depression in newborn mice

Mutant mice lacking NMDA receptor 1 subunit (NR1) showed marked depression of respiratory and suckling activities in vivo and overexpression of synapt ic long-term depression (LTD) in a brainstem cardiorespiratory-related regi on (nucleus tractus solitarius) in vitro. Pharmacological blockade of NMDA receptors in normal newborn mice mimicked the depression in suckling activi ty but not respiratory depression in vivo or brainstem LTD in vitro. Result s at the behavioral and cellular levels demonstrate that NMDA receptor defi ciency during prenatal development may unleash an anomalous form of NMDA re ceptor-independent LTD along with life-threatening respiratory depression c onsequences in the newborn. These findings raise the specter of cardiorespi ratory dysregulation with increased risks of morbidity and mortality in the infant as a result of premature births or genetic or drug-induced NMDA rec eptor antagonism during pregnancy.