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 synaptic long-term depression (LTD) in a brainstem cardiorespiratory-related region (nucleus tractus solitarius) in vitro. Pharmacological blockade of NMDA receptors in normal newborn mice mimicked the depression in suckling activity but not respiratory depression in vivo or brainstem LTD in vitro. Results at the behavioral and cellular levels demonstrate that NMDA receptor deficiency during prenatal development may unleash an anomalous form of NMDA receptor-independent LTD along with life-threatening respiratory depression consequences in the newborn. These findings raise the specter of cardiorespiratory dysregulation with increased risks of morbidity and mortality in the infant as a result of premature births or genetic or drug-induced NMDA receptor antagonism during pregnancy.