AMPA glutamate receptors and respiratory control in the developing rat: anatomic and pharmacological aspects

Abstract

The developmental role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate receptors in respiratory regulation remains undefined. To study this issue, minute ventilation (V(E)) was measured in 5-, 10-, and 15-day-old intact freely behaving rat pups using whole body plethysmography during room air (RA), hypercapnic (5% CO(2)), and hypoxic (10% O(2)) conditions, both before and after administration of the non-N-methyl-D-aspartate (NMDA) receptor antagonist 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX; 10 mg/kg ip). In all age groups, V(E) during RA was unaffected by NBQX, despite reductions in breathing frequency (f) induced by increases in both inspiratory and expiratory duration. During hypoxia and hypercapnia, V(E) increases were similar in both NBQX and control conditions in all age groups. However, tidal volume was greater and f lower after NBQX. To determine if AMPA receptor-positive neurons are recruited during hypoxia, immunostaining for AMPA receptor (GluR2/3) and c-fos colabeling was performed in caudal brain stem sections after exposing rat pups at postnatal ages 2, 5, 10, and 20 days, and adult rats to room air or 10% O(2) for 3 h. GluR2/3 expression increased with postnatal age in the nucleus of the solitary tract (NTS) and hypoglossal nucleus, whereas a biphasic pattern emerged for the nucleus ambiguus (NA). c-fos expression was enhanced by hypoxia at all postnatal ages in the NTS and NA and also demonstrated a clear maturational pattern. However, colocalization of GluR2/3 and c-fos was not affected by hypoxia. We conclude that AMPA glutamate receptor expression in the caudal brain stem is developmentally regulated. Furthermore, the role of non-NMDA receptors in respiratory control of conscious neonatal rats appears to be limited to modest, albeit significant, regulation of breathing pattern.

PDGF-β Receptor Expression in the Dorsocaudal Brainstem Parallels Hypoxic Ventilatory Depression in the Developing Rat

“…1 and 2). As previously shown (2,7,15,16), an age-dependent increase in the magnitude of the HVR was apparent. However, the magnitude of HVR was unchanged by pretreatment with CGP 57148B (Figs.…”

“…For hypercapnic ventilatory challenges, 5% CO 2 balance room air was administered for 30 min after the same experimental template as that described for hypoxic runs. This time frame provides adequate expression of HVD and does not modify the ventilatory response to a subsequent challenge (7,15,16).…”

“…However, whereas glutamate receptors are critical to HVR in the adult rat (20,21), their contribution emerges as much more modest in the neonatal rat (15,16). Although reduced expression of glutamate receptors within some of the caudal brainstem regions involved in HVR may certainly play a role in the developmental characteristics of HVR, it is clear that after the peak excitatory ventilatory effects of hypoxia have occurred, HVD will emerge rather rapidly in the immature rat.…”

Postnatal expression of neurotransmitters, receptors, and cytochrome oxidase in the rat pre-Bötzinger complex

“…It is maximal at P7 in the spinal trigeminal tract but at P17 in the hippocampal commissure (25). Significant maturation of the ventilatory control system in the rat occurs between P10 and P15 (49).…”

Protein tyrosine kinase regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons

“…Antagonists of the AMPA receptor have been shown to attenuate injuries to neuron or glia cells during brain hypoxia (Follett et al, 2000). Hypoxia respiratory responses were inhibited after the AMPA receptor was blocked (Whitney et al, 2000). Microinjection of an AMPA receptor agonist in the nucleus tractus solitaries increased ventilation by 50% under sustained hypoxia, while an AMPA receptor antagonist abolished this effect.…”