Role of NMDA receptors in development of respiratory control

Abstract

The N-methyl-D-aspartate (NMDA) receptor has many functions throughout the central nervous system (CNS) including its role within the centers controlling respiration. Although NMDA receptors are important for normal breathing, they are specifically active under conditions of stress, such as hypoxia. Consistent with its role in other neurological functions, the NMDA receptor is also important to the prenatal development of normal neurological pathways for the control of ventilation. The importance of NMDA receptors to both normal breathing and stress responses is demonstrated by recent observations of antenatal effects of disturbances to the NMDA receptor which disrupts normal breathing as well as causing reduced ventilatory responses during stress in newborns. These characteristics fit with the known NMDA influences on neuronal development and plasticity. The methods used to evaluate these functions have mainly included pharmacological agents for activation (agonists) or depression (antagonists) of NMDA receptors. NMDA receptor expression has also been measured histologically, and more recently knockout animal models have been used to provide additional functional information.