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 onto 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 behaviours 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 signalling and autonomic function.

Keywords: autonomic; clock genes; synaptic throughput; vagus.