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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Astrocytic modulation of glutamatergic synaptic transmission is reduced in NTS of rats submitted to short-term sustained hypoxia

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Accorsi-Mendonca, Daniela [1] ; Bonagamba, Leni G. H. [1] ; Machado, Benedito H. [1]
Total Authors: 3
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Journal of Neurophysiology; v. 121, n. 5, p. 1822-1830, MAY 2019.
Web of Science Citations: 0

Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the arterial partial pressure of O-2 back to the physiological range. We evaluated the effect of SH (fraction of inspired O-2 = 0.10, 24 h) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarii (NTS). Tractus solitarius (TS) fiber stimulation induced glutamatergic currents in neurons and astrocytes. SH increased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) {[}-183 +/- 122 pA (n = 10) vs. -353 +/- 101 pA (n = 10)] and N-methyl-D-aspartate (NMDA) current amplitude {[}61 +/- 10 pA (n = 7) vs. 102 +/- 37 pA (n = 10)]. To investigate the effects of SH, we used fluoroacetate (FAC), an astrocytic inhibitor, which revealed an excitatory modulation on AMPA/kainate current and an inhibitory modulation of NMDA current in control rats. SH blunted the astrocytic modulation of AMPA {[}artificial cerebrospinal fluid (aCSF): -353 +/- 101 pA vs. aCSF +/- FAC: -369 +/- 76 pA (n = 10)] and NMDA currents {[}aCSF: 102 +/- 37 pA vs. aCSF + FAC: 108 +/- 32 pA (n = 10)]. SH increased AMPA current density {[}control: -6 +/- 3.5 pA/pF (n = 6) vs. SH: -20 +/- 12 pA/pF (n = 7)], suggesting changes in density, conductance, or affinity of AMPA receptors. SH produced no effect on astrocytic resting membrane potential, input resistance, and AMPA/kainate current. We conclude that SH decreased the neuron-astrocyte interaction at the NTS level, facilitating the glutamatergic transmission, which may contribute to the enhancement of cardiovascular and respiratory responses to baro- and chemoreflexes activation in SH rats. NEW \& NOTEWORTHY Using an electrophysiological approach, we have shown that in nucleus tractus solitarii (NTS) from control rats, astrocytes modulate the AMPA and NMDA currents in NTS neurons, changing their excitability. Sustained hypoxia (SH) increased both glutamatergic currents in NTS neurons due to 1) a reduction in the astrocytic modulation and 2) an increase in the density of AMPA receptors. These new findings show the importance of neuron-astrocyte modulation in the excitatory synaptic transmission in NTS of control and SH rats. (AU)

FAPESP's process: 13/06077-5 - Changes in the neural networks involved with the generation and control of sympathetic and respiratory activities in different experimental models of hypoxia
Grantee:Benedito Honorio Machado
Support type: Research Projects - Thematic Grants