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 (0.1 Hz) to ultra-fast ripples (600 Hz). 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 24 h (< 0.001 Hz). 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.

The circadian clock: a tale of genetic–electrical interplay and synaptic integration

“…This current is driven by the rhythmic expression of NCA Localization Factor -1, providing an example of signaling pathway linking the molecular clock to ion channel function [9]. This channel pathway is a new addition to the families of cation channels that provide depolarizing forces to SCN neurons during the day, elevating their resting membrane potential and increasing firing rate [10–12]. The L-type calcium channel is another key cation channel involved in sustaining excitation in SCN neurons [1,8].…”

“…This provides yet another example of a pathway where the TTFL can influence ion channel activity. Some potassium channels may reduce their conductivity to support such depolarization during the day [10–12]. For example, a reduction in the activity of the small-conductance calcium-activated potassium channels transits a proportion of daytime SCN neurons into hyperexcitation and depolarization blockade states, where they ceased firing [1,14].…”

“…In the evening, the activity of a number of potassium currents peaks to hyperpolarize and silence clock neurons [10–12]. Reduction of Per1 activity by antisense oligonucleotides suppressed firing of SCN neurons by reducing intracellular calcium levels and the conductance of the large calcium-activated potassium currents (BK; [15]).…”

Copper in the suprachiasmatic circadian clock: A possible link between multiple circadian oscillators

“…A unique feature of the SCN is the diurnal increase in neuronal activity and action potential firing rate that peaks around midsubjective day (rev. in Belle & Diekman, ; Herzog et al., ). The clock regulates the resting membrane potential of SCN neurons, hence their circadian electrical activity rhythms, by day–night changes in expression, localization, and function of various ion channels, transporters/pumps, and extra‐neuronal factors (Belle & Diekman, ; Colwell, ; Farajnia, Meijer, & Michel, ; Wang, Yang, & Huang, ).…”

Daytime light enhances the amplitude of circadian output in a diurnal mammal

“…In mammals, near 24h (circadian) rhythms in physiology and behaviour are orchestrated by a master clock located in the hypothalamic suprachiasmatic nuclei (SCN) (1,2). The SCN clock generates a circadian rhythm in electrical activity, with neurons significantly more excited during the day (up-state) than at night (down-state) (3,4). This endogenous rhythm is synchronised (entrained) to the external 24h light-dark cycle via input from the retina (5).…”