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Chronic intermittent hypoxia (CIH) alters the neuronal response to norepinephrine (NE) in the pre‐Bötzinger complex (pre‐BötC)
Author(s) -
Garcia Alfredo J.,
Prabhakar Nanduri,
Ramirez JanMarino
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.755.1
Subject(s) - bursting , brainstem , electrophysiology , population , norepinephrine , chemistry , extracellular , endocrinology , medicine , premovement neuronal activity , hypoxia (environmental) , neuroscience , catecholamine , biology , oxygen , biochemistry , environmental health , organic chemistry , dopamine
The impact of CIH on mechanisms underlying the rhythmogenesis of breathing is poorly understood. This ongoing study, tests the hypothesis that CIH disrupts normal neuronal activity in the pre‐BötC. Neonatal mice (P0–P1) were exposed to ~8hrs. of intermittent hypoxia for 7–10 days. After exposure to CIH, brainstem slices containing the pre‐BötC were prepared for either electrophysiological or biochemical experiments. Extracellular recordings from the pre‐BötC show that CIH causes an increase in the irregularity of population burst frequency. Moreover, application of norepinephrine (NE) produces unstable augmentation of population burst amplitude. Intracellular recordings from within the CIH‐conditioned pre‐BötC demonstrate that individual neurons reliably firing action potentials in phase with the rhythm, intermittently fail to produce action potentials when exposed NE. These findings indicate that CIH promotes a state where the coupling of individual neurons to the rest the neuronal network is decreased leading to the unstable amplitude modulation of population bursts during exposure to NE. Biochemical analysis reveals that CIH activates HIF‐1 alpha and increases lipid peroxidation within the pre‐BötC. Hence, the changes in the neuronal response to NE may be the result of adaptations to repeated hypoxic and oxidative stresses produced by CIH.