The Journal of Neuroscience, 0000, 20:RC73:1-6
RAPID COMMUNICATION
NMDA Receptor Activity In Utero Averts Respiratory
Depression and Anomalous Long-Term Depression in Newborn
Mice
Chi-Sang
Poon1,
Zhongren
Zhou1, and
Jean
Champagnat2
1 Harvard-MIT Division of Health Sciences and
Technology, Massachusetts Institute of Technology, Cambridge,
Massachusetts 02139, and 2 Neurobiologie
Génétique et Intégrative, Centre National de la
Recherche Scientifique, 91198 Gif-sur-Yvette, France
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.
Key words:
NMDA receptor; NR1 knock-out; synaptic long-term
depression; respiratory failure; nucleus tractus solitarius; prenatal
neural development; newborn mice
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