GABA and Glycine: Fine Tuning for Inhibitory Control of Brainstem RVLM Neurons

Abstract

Presympathetic neurons in the rostral ventrolateral medulla (RVLM) are best known for their contribution to the control of sympathetic nervous system and homeostatic functions of the body. Both glycine and GABA were identified as fast inhibitory neurotransmitters in the RVLM. GABA is essential for the control of the excitability of neurons, while glycine also inhibits neurons in the RVLM, and thus control sympathetic output. Despite the critical role of GABA and glycine as inhibitory neurotransmitters, surprisingly little is known about the mechanisms of GABA and glycine release and/or co‐release. Using whole‐cell patch‐clamp recordings from presympathetic neurons identified with PRV‐152, we examined GABAergic and glycinergic inhibitory mechanisms in rat brainstem slices containing RVLM neurons. We tested the hypothesis that the release of glycine is associated with the activity of neuronal network. We found that inhibitory postsynaptic currents (IPSCs) recorded from RVLM neurons composed from both GABAergic and glycinergic events. In steady state conditions, GABA is the predominant inhibitory neurotransmitter in the RVLM. Interestingly, after activation of the inhibitory network, we found that GABAergic and glycinergic neurotransmission were reversed. Under resting condition, the proportion of glycinergic IPSCs was less than 10% of the total IPSCs. Activation of the inhibitory network produced saturation of inhibitory events mediated by GABA and increased the average frequency of glycine‐mediated IPSCs. After network activation, glycinergic IPSCs represent more than half of the total IPSCs in the RVLM. Our data suggest that after saturation of GABA, glycinergic inhibition provides a secondary synaptic inhibition in presympathetic RVLM neurons. This novel mechanism has the potential for fine tuning of the sympathetic output controlling homeostatic functions.Support or Funding InformationSupported by NHLBI R01HL122829