Circadian rhythms generated in the brain synchronize physiological and behavioral responses to environmental light / dark cycles, including the maintenance of autonomic tone and key reflex pathways. The hypothalamic suprachiasmatic nucleus (SCN) is the master brain clock and achieves rhythmicity through endocrine and neural control of the autonomic nervous system. While many studies have focused on understanding rhythm generation in the SCN, much less is known about extra-SCN clock mechanisms. The purpose of this study was to investigate the nucleus of the solitary tract (NTS) of the brainstem as a key candidate for the extra-SCN rhythmic control of the autonomic nervous system and feeding.
The NTS receives direct visceral inputs through the vagus nerve and is directly responsive to circulating factors and hormones; positioning it as a key integrator of circadian rhythms and visceral status. In these studies we utilized molecular biology (qPCR), PER1 driven in vitro luciferase imaging, and whole cell patch-clamp electrophysiology on primary vagal afferent neurons and brainstem slices containing the solitary tract from rats and mice.
To begin, we investigated the basic components of the molecular circadian clock using quantitative PCR and in vitro luciferase activity as reporters of clock gene expression. From these approaches we determined the NTS expresses a robust molecular clock mechanism that can persist for many days independent of extrinsic coordination from the light / dark cycle or SCN. We extended these results using patch-clamp electrophysiology and demonstrated the additional presence of rhythmic glutamatergic neurotransmission onto NTS neurons.
Together these observations suggest the NTS possesses intrinsic clock mechanism that may contribute to circuit activity, feeding, and autonomic control throughout the day.