Abstract
Chronic intermittent hypoxia (CIH), an animal model of sleep apnea, has been shown to alter the activity of second-order chemoreceptor neurons in the caudal nucleus of the solitary tract (cNTS). Although numerous studies have focused on excitatory plasticity, few studies have explored CIH-induced plasticity impacting inhibitory inputs to NTS neurons, and the roles of GABAergic and glycinergic inputs on heightened cNTS excitability following CIH are unknown. In addition, changes in astrocyte function may play a role in cNTS plasticity responses to CIH. This study tested the effects of a 7-day CIH protocol on miniature inhibitory postsynaptic currents (mIPSCs) in cNTS neurons receiving chemoreceptor afferents. Normoxia-treated rats primarily displayed GABA mIPSCs, whereas CIH-treated rats exhibited a shift toward combined GABA/glycine-mediated mIPSCs. CIH increased glycinergic mIPSC amplitude and area. This shift was not observed in dorsal motor nucleus of the vagus neurons or cNTS cells from females. Immunohistochemistry showed that strengthened glycinergic mIPSCs were associated with increased glycine receptor protein and were dependent on receptor trafficking in CIH-treated rats. In addition, CIH altered astrocyte morphology in the cNTS, and inactivation of astrocytes following CIH reduced glycine receptor-mediated mIPSC frequency and overall mIPSC amplitude. In cNTS, CIH produced changes in glycine signaling that appear to reflect increased trafficking of glycine receptors to the cell membrane. Increased glycine signaling in cNTS associated with CIH also appears to be dependent on astrocytes. Additional studies will be needed to determine how CIH influences glycine receptor expression and astrocyte function in cNTS.NEW & NOTEWORTHY Chronic intermittent hypoxia (CIH) has been used to mimic the hypoxemia associated with sleep apnea and determine how these hypoxemias influence neural function. The nucleus of the solitary tract is the main site for chemoreceptor input to the CNS, but how CIH influences NTS inhibition has not been determined. These studies show that CIH increases glycine-mediated miniature IPSCs through mechanisms that depend on protein trafficking and astrocyte activation.