Developmental changes in NMDA receptor subunits alter burst frequency of neonatal rat brainstem slices containing the preBötzinger Complex

Abstract

N‐methyl‐d‐aspartate receptors (NMDARs) are crucial in controlling synaptic excitation and plasticity at glutamatergic synapses in the CNS. NMDARs are composed of multiple NR1 and at least one of four NR2 subunits and previous studies have shown development changes in NMDARs. In the perinatal brain, NR2B subunits predominate, however these subunits are supplemented with NR2A/NR2C subunits. We hypothesized that respiratory rhythm in the brainstem of postnatal rats (P0–P3), is developmentally modulated by NMDAR subunit changes in the preBötzinger Complex (pBC). We prepared pBC‐containing slices from Sprague Dawley rat pups (P0 to P5) and measured changes in hypoglossal (XII) rootlet output and characterized the switch from NR2B‐ to NR2A‐containing NMDARs by bath application of 10 μM ifenprodil, a noncompetitive inhibitor of the NR2B subunit. Our results show a significant decrease (p < 0.05; compared to baseline) in inter‐burst interval after application of ifenprodil in P0–P3 (n=3) slices with no significant change in animals > P3. This suggests that NR2B‐containing NMDARs play a role in the modulation of respiratory rhythm early in life. Support: This work was supported by NIH/NHLBI grant HL081622