Molecular and Cellular Networks in The Suprachiasmatic Nuclei

Abstract

Why do we experience the ailments of jetlag when we travel across time zones? Why is working night-shifts so detrimental to our health? In other words, why can’t we readily choose and stick to non-24 h rhythms? Actually, our daily behavior and physiology do not simply result from the passive reaction of our organism to the external cycle of days and nights. Instead, an internal clock drives the variations in our bodily functions with a period close to 24 h, which is supposed to enhance fitness to regular and predictable changes of our natural environment. This so-called circadian clock relies on a molecular mechanism that generates rhythmicity in virtually all of our cells. However, the robustness of the circadian clock and its resilience to phase shifts emerge from the interaction between cell-autonomous oscillators within the suprachiasmatic nuclei (SCN) of the hypothalamus. Thus, managing jetlag and other circadian disorders will undoubtedly require extensive knowledge of the functional organization of SCN cell networks. Here, we review the molecular and cellular principles of circadian timekeeping, and their integration in the multi-cellular complexity of the SCN. We propose that new, in vivo imaging techniques now enable to address these questions directly in freely moving animals.

Uncovering the Roles of Clocks and Neural Transmission in the Resilience of Drosophila Circadian Network

“…In summary, the present study highlights the remarkable resilience of Drosophila circadian pacemaker circuit, the property conserved in mammals (El Cheikh Hussein et al, 2019). Our findings support the emerging view that the topology of the pacemaker circuit is not rigid, as in the classical Mand E-oscillator model, but rather flexible, assigning different neuronal subgroups the task of pacemaking in order to achieve the resilience.…”

Identifying Transcription Factor Combinations to Modulate Circadian Rhythms by Leveraging Virtual Knockouts on Transcription Networks

“…In the mammalian circadian organization, the SCN-master pacemaker presides at the top of the hierarchy ( Panda et al., 2002 ; Storch et al., 2002 ; Antle and Silver, 2005 ; Fuller et al., 2006 ; Sobel et al., 2017 ; El Cheikh Hussein et al., 2019 ). SCN is primarily stimulated by the light entrainments around the day/night periods and passing the cues to a dispersed network of peripheral clocks located in distal tissues in the mammalian systems.…”

“…SCN is primarily stimulated by the light entrainments around the day/night periods and passing the cues to a dispersed network of peripheral clocks located in distal tissues in the mammalian systems. With the day/night cycles, the SCN-master pacemaker plays as a vital timekeeper to regulate sleep/wake cycles and many crucial physiological activities ( Antle and Silver, 2005 ; Fuller et al., 2006 ; El Cheikh Hussein et al., 2019 ). Temporal tuning of the distal tissue-specific peripheral clocks upon robust expressions of circadian genes is indeed tricky to be explicated at the dynamic frame.…”

Understanding Quantitative Circadian Regulations Are Crucial Towards Advancing Chronotherapy

“…It consists of a network of functionally and phenotypically differentiated cells [47]. This SCN network functions as a master pacemaker for controlling the body’s indigenous rhythms, also known as circadian rhythms, being at the top of the structural hierarchy of the circadian systems (Figure 2) [48]. Also, this region is important for rhythmic hormone secretion and locomotor activity [49].…”