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

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. KEY POINTS: Vagal afferent neurons relay information from peripheral organs to the brainstem nucleus of the solitary tract (NTS) to initiate autonomic reflex pathways as well as providing important controls of food intake, digestive function, and energy balance. Vagally mediated reflexes and behaviors are under strong circadian regulation. Diurnal fluctuations in presynaptic vesicle release pathways and postsynaptic membrane conductances provide nuanced control over NTS action potential firing and vagal synaptic throughput. Coordinated pre- / postsynaptic changes represent a fundamental mechanism mediating daily changes in vagal afferent signaling and autonomic function. Abstract figure legend Circadian regulation of presynaptic glutamate release and postsynaptic membrane resistance shape basal action potential firing and synaptic throughput across the light / dark cycle at vagal afferent to NTS synapses. During the light phase afferent spontaneous glutamate release is elevated and the postsynaptic NTS neuron is depolarized resulting in constitutive postsynaptic action potential firing. Whereas in the dark phase presynaptic glutamate release is lower and the postsynaptic NTS membrane is hyperpolarized with a greater membrane resistance. This results in lower basal action potential firing but greater afferent to NTS synaptic throughput. These coordinated pre- and postsynaptic neurophysiological changes translate circadian rhythms to functional changes in synaptic. This article is protected by copyright. All rights reserved.