Enhancement of the Evoked Excitatory Transmission in the Nucleus Tractus Solitarius Neurons after Sustained Hypoxia in Mice Depends on A2A Receptors

first synapses of the afferents of peripheral chemoreceptors are located in the Nucleus Tractus Solitarius (NTS) and there is evidence that short-term sustained hypoxia (SH - 24 h, FiO2 0.1) facilitates glutamatergic transmission in NTS neurons of rats. Adenosine is an important neuromodulator of synaptic transmission and hypoxia contributes to increase its extracellular concentration. The A2A receptors mediate the excitatory actions of adenosine and are active players in the modulation of neuronal networks in the NTS. Herein, we used knockout mice for A2A receptors (A2AKO) and electrophysiological recordings of NTS neurons were performed to evaluate the contribution of these receptors in the changes in synaptic transmission in NTS neurons of mice submitted to SH. The membrane passive properties and excitability of NTS neurons were not affected by SH and were similar between A2AKO and wild-type mice. The overall amplitude of spontaneous glutamatergic currents in NTS neurons of A2AKO mice was lower than in Balb/c WT mice. SH increased the amplitude of evoked glutamatergic currents of NTS neurons from WT mice by a non-presynaptic mechanism, but this enhancement was not observed in NTS neurons of A2AKO mice. Under normoxia, the amplitude of evoked glutamatergic currents was similar between WT and A2AKO mice. The data indicate that A2A receptors (a) modulate spontaneous glutamatergic currents, (b) do not modulate the evoked glutamatergic transmission in the NTS neurons under control conditions, and (c) are required for the enhancement of glutamatergic transmission observed in the NTS neurons of mice submitted to SH.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.