Circadian regulation of glutamate release pathways shapes synaptic throughput in the brainstem nucleus of the solitary tract (NTS)

Abstract

Circadian regulation of autonomic reflex pathways pairs physiological function with the daily light cycle. The brainstem nucleus of the solitary tract (NTS) is a key candidate for rhythmic control of the autonomic nervous system. Here we investigated circadian regulation of NTS neurotransmission and synaptic throughput using patch-clamp electrophysiology in brainstem slices from mice. We found that spontaneous quantal glutamate release on to NTS neurons showed strong circadian rhythmicity, with the highest rate of release during the light phase and the lowest in the dark, that were sufficient to drive day / night differences in constitutive postsynaptic action potential firing. In contrast, afferent-evoked action potential throughput was enhanced during the dark and diminished in the light. Afferent-driven synchronous release pathways showed a similar decrease in release probability that did not explain the enhanced synaptic throughput during the night. However, analysis of postsynaptic membrane properties revealed diurnal changes in conductance; which, when coupled with the circadian changes in glutamate release pathways, tuned synaptic throughput between the light and dark phases. These coordinated pre- / postsynaptic changes encode nuanced control over synaptic performance and pair NTS action potential firing and vagal throughput with time of day.

Sleep tight, beat right: Does nucleus of the solitary tract circadian rhythmicity influence blood pressure and sleep regulation?

“…As noted by Ragozzino et al. (2023), higher rates of synaptic transmission and basal NTS firing rates during the daytime reflect increased sensitivity to incoming signals. Greater spontaneous firing during the daytime when the mouse is at rest ensures the NTS is persistently activated, contributing to lowered blood pressure at rest.…”

“…Spontaneous vesicle release may regulate synaptic tone and decrease postsynaptic sensitivity to incoming peripheral afferent feedback, such as an increase in blood pressure from baroreceptor firing. This would lead to a relatively weak baroreflex response, with less parasympathetic stimulation and sympathetic inhibition than in the absence of spontaneous release (Ragozzino et al., 2023). While blood pressure and end‐organ function oscillate throughout the day, it is unknown to what effect neurophysiological fluctuations within NTS might modify their functioning.…”

“…In a recent article published in The Journal of Physiology , Ragozzino et al. (2023) investigated whether pre‐ and postsynaptic processes in the NTS varied across the circadian cycle. The authors isolated brainstems and nodose ganglia at six time points from mice kept in 12:12 h light–dark or 12:12 h dark–dark environments.…”

“…The study by Ragozzino et al. (2023) provides insight into the integrative regulation of both cardiovascular function and sleep–wake brain states in healthy and clinical populations. It has been shown that specific NTS neurons respond to increased blood pressure, subsequently promoting a reduction in heart rate and blood pressure, and prompting transitions from wakefulness to sleep (Yao et al., 2022).…”

“…The work by Ragozzino et al. (2023) provides context to the relevance of these NTS circuits during phases of inactivity when blood pressure is known to dip. Ragozzino et al.…”