Tonic GABAergic inhibition of RVLM neurons: a novel target for sympathetic control (1172.3)

Abstract

The rostral ventrolateral medulla (RVLM) is a critical component of the sympathetic nervous system regulating homeostatic functions including arterial blood pressure (ABP). GABAA receptors mediate the majority of inhibition in the brain and GABAergic inhibition of preautonomic neurons in the RVLM is well accepted. Decreased inhibition of RVLM neurons increases sympathetic nervous system activity and thereby elevates ABP. Despite our increasing understanding of the functional significance of GABAA receptors in the regulation of neuronal excitability, the mechanisms underlining synaptic and extrasynaptic control of preautonomic neurons in the RVLM is unknown. Using the transsynaptic retrograde viral tracer, PRV‐152, we identified preautonomic neurons in the RVLM. We found that RVLM neurons displayed persistent, tonic current to GABA, via GABAA receptors, in the absence of large‐scale phasic neurotransmission using whole‐cell patch‐clamp recordings. Application of the GABAA receptor blocker bicuculline (30 µM), revealed a robust somatic tonic inhibitory current mediated by extrasynaptic GABAA receptors with an average amplitude of 196.3 ± 39.3 pA. Our data suggest that extrasynaptic tonic current mediated by GABAA receptors plays a major role in determining the resting membrane potential and firing activity of preautonomic neurons in the RVLM.Grant Funding Source: NIH P30GM103337