Postnatal age influences how Intermittent Hypoxia impacts hippocampal synaptic plasticity and NMDA receptor subunit expression.

The ability to scale synaptic strength supports the robustness and flexibility of learning and memory throughout a lifetime. Intermittent Hypoxia (IH) is a hallmark of several clinical conditions such as sleep apnea and apneas of prematurity. These conditions are associated with neurocognitive deficits. We recently demonstrated that IH phenocopies aging by causing oxidative stress and suppressing NMDAr-dependent synaptic plasticity. However, the basis of these IH-dependent phenomena appears to be driven through a mechanism independent of aging where IH causes downregulation of GluN1, the obligatory subunit of NMDAr. Based on these findings, we sought do determine how IH exposure during early postnatal life impacts hippocampal neurophysiology. Electrophysiological studies and protein analyses were performed using hippocampal brain slices taken from mice (P14-P15) exposed to ten days of neonatal IH (nIH, starting at P4-P5). In contrast to the IH-mediated effects in the adult hippocampus, nIH neither suppressed GluN1 expression nor eliminated NMDAr-dependent synaptic plasticity, but rather caused NMDAr subunit remodeling by causing GluN2A downregulation and GluN2B upregulation. Moreover, the preserved synaptic plasticity after nIH was maintained was dependent on a larger contribution of GluN2B. These findings indicate that postnatal age is a significant factor influencing the mechanistic consequences of IH on hippocampal neurophysiology.