TY - JOUR
T1 - Chronic intermittent hypoxia enhances glycinergic inhibition in nucleus tractus solitarius
AU - Jia, Shuping
AU - Rybalchenko, Nataliya
AU - Kunwar, Kishor
AU - Farmer, George E.
AU - Little, Joel T.
AU - Toney, Glenn M.
AU - Cunningham, J. Thomas
N1 - Funding Information:
This study was supported by grants P01 HL088052 and R01 HL155977 to G.E.F., G.M.T., and J.T.C.
Publisher Copyright:
Copyright © 2022 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - GABA
KW - astrocytes
KW - chemoreceptor
KW - protein trafficking
UR - http://www.scopus.com/inward/record.url?scp=85142403338&partnerID=8YFLogxK
U2 - 10.1152/jn.00241.2022
DO - 10.1152/jn.00241.2022
M3 - Article
C2 - 36321700
AN - SCOPUS:85142403338
SN - 0022-3077
VL - 128
SP - 1383
EP - 1394
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 6
ER -