Neuronal oscillations on an ultra-slow timescale: daily rhythms in electrical activity and gene expression in the mammalian master circadian clockwork.

Abstract

Neuronal oscillations of the brain, such as those observed in the cortices and hippocampi of behaving animals and humans, span across wide frequency bands, from slow delta waves (0.1Hz) to ultra-fast ripples (600Hz). Here, we focus on ultra-slow neuronal oscillators in the hypothalamic suprachiasmatic nuclei (SCN), the master daily clock that operates on interlocking transcription-translation feedback loops to produce circadian rhythms in clock gene expression with a period of near 24h (<0.001Hz). This intracellular molecular clock interacts with the cell's membrane through poorly understood mechanisms to drive the daily pattern in the electrical excitability of SCN neurons, exhibiting an up-state during the day and a down-state at night. In turn, the membrane activity feeds back to regulate the oscillatory activity of clock gene programs. In this review, we emphasise the circadian processes that drive daily electrical oscillations in SCN neurons, and highlight how mathematical modelling contributes to our increasing understanding of circadian rhythm generation, synchronisation and communication within this hypothalamic region and across other brain circuits.