The nucleus of the solitary tract (NTS) receives inputs from both arterial chemoreceptors and central noradrenergic neural structures activated during hypoxia. We investigated norepinephrine (NE) modulation of chemoreceptor afferent integration after a chronic exposure to sustained hypoxia (CSH) (7-8 d at 10% FI0 2). Whole-cell recordings of NTS second-order neurons identified by DiA (1,1′dilinoleyl-3,3,3′, 3′ -tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate) labeling of carotid bodies were obtained in a brain slice. Electrical stimulation of the solitary tract was used to evoke EPSCs. CSH exposure increased evoked EPSC (eEPSC) amplitude via both presynaptic and postsynaptic mechanisms. NE dose dependently decreased the amplitude of eEPSCs. NE increased the paired-pulse ratio of eEPSCs and reduced the frequency of miniature EPSCs, suggesting a presynaptic mechanism. EC 50 of NE inhibition of eEPSCs was lower in CSH cells (3.0 ± 0.9 μM; n = 5) than in normoxic (NORM) cells (7.6 ± 1.0 μM;n = 7; p < 0.01). NE (10 μM) elicited greater inhibition of eEPSCs in CSH cells (63 ± 2%; n = 16) than NORM cells (45 ± 3%; n = 21; p < 0.01 ). The a-adrenoreceptor antagonist phentolamine abolished NE inhibition of eEPSCs. CSH enhanced the α2-adrenoreceptor agonist clonidine-mediated inhibition (3 μM; NORM, 23 ±2%, n = 5 vs CSH, 44 ± 5%, n = 4;p < 0.05) but attenuated al-adrenoreceptor agonist phenylephrine-mediated inhibition (40 μM; NORM, 36 ± 2%, n = 11 vs CSH, 26 ± 4%, n = 6; p< 0.05). The a2-adrenoreceptor antagonist yohimbine abolished CSH-induced enhancement of NE inhibition of eEPSCs. These results demonstrate that CSH increases evoked excitatory inputs to NTS neurons receiving arterial chemoreceptor inputs. CSH also enhances NE inhibition of glutamate release from inputs to these neurons via presynaptic α2-adrenoreceptors. These changes represent central neural adaptations to CSH.
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