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Co‐release of inhibitory neurotransmitters in the RVLM
Author(s) -
Gao Hong,
Desmoulins Lucie D.,
Zsombok Andrea,
Derbenev Andrei V.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04868
Subject(s) - rostral ventrolateral medulla , glycine receptor , strychnine , inhibitory postsynaptic potential , gabaergic , photostimulation , bicuculline , chemistry , postsynaptic potential , neuroscience , gaba receptor antagonist , 4 aminopyridine , medulla oblongata , antagonist , glycine , biology , receptor , endocrinology , central nervous system , biochemistry , potassium channel , amino acid
Sympathetic nerve activity (SNA) and blood pressure (BP) are largely determined by the level of excitability of presympathetic neurons (C1 neurons) in the rostral ventrolateral medulla (RVLM). GABAergic inhibition in the RVLM is the primary mechanism for depressor and sympathoinhibitory responses; however, the role of glycinergic inhibition in the control of RVLM excitability is unknown. There is evidence that both, GABA and glycine efficiently inhibit RVLM neurons, but functional evidence for their co‐release or the mechanism of co‐inhibition is lacking. In our study we used both male and female glycine transporter 2 Cre (GlyT2‐Cre) mice. Glycinergic neurons sending projections to the RVLM were identified with viral labeling. Targeted expression of channelrhodopsin 2 (ChR2) in GlyT2‐expressing neurons and whole‐cell recordings from presympathetic RVLM neurons were used to study the mechanism of glycine release. We found that under steady‐state conditions spontaneous inhibitory postsynaptic current (sIPSC) are primarily mediated by GABA. Photostimulation of glycinergic fibers expressing GlyT2 in the RVLM resulted in evoked IPSCs with both glycinergic and GABAergic components. The time course of synaptic signaling were identical for the two transmitters. Bath application of GABA A receptors antagonist bicuculline (10 μM) or glycine receptor antagonist strychnine (1 μM) revealed that ~40% of the evoked inhibitory currents are GABAergic. High frequency photostimulation (20 Hz) of co‐releasing inhibitory fibers produced a short‐term synaptic depression. Blockade of GlyT2 prevented the glycinergic component of the light evoked IPSCs. In this study we showed that GABA and glycine are co‐released in the RVLM. Our findings suggest that the two neurotransmitters may be functionally interchangeable or complement each other, and thus provide diverse mechanisms for maintaining inhibitory homeostasis.