The choroid plexus is an important circadian clock component

Abstract

Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of “twist” circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.

Keeping time in the lamina terminalis: Novel oscillator properties of forebrain sensory circumventricular organs

“…Circadian rhythms in the OVLT have previously been demonstrated in clock gene bioluminescence [25][26][27] and Per3. Circadian rhythms in the SFO and OLVT are exceptionally sustained in culture, lasting up to 21 days following the treatment with forskolin.…”

“…25,27 To address this gap in our knowledge, we used a sensitive imaging system and visualized PER2-driven bioluminescence in coronal brain slices containing the SFO ( Figure 1Bc). 25,27 To address this gap in our knowledge, we used a sensitive imaging system and visualized PER2-driven bioluminescence in coronal brain slices containing the SFO ( Figure 1Bc).…”

“…21,22 The SCN has direct neural connections with both the SFO and OVLT, 23 and vasopressin neurons of the SCN drive nocturnal anticipatory thirst through excitation of OVLT neurons. [25][26][27] Here, we used ex vivo PER2::LUC bioluminescence imaging and in vivo gene expression to broadly assess the circadian rhythmicity of the SFO and OVLT. [25][26][27] Here, we used ex vivo PER2::LUC bioluminescence imaging and in vivo gene expression to broadly assess the circadian rhythmicity of the SFO and OVLT.…”

Choroid plexus is an additional source of melatonin in the brain

“…Furthermore, in a previous study from our group we have demonstrated that the CP holds a functional circadian clock that is controlled by the light/dark cycle and sex steroid hormones . More recently, the demonstration that the CP encloses a circadian clock remarkably robust, and with higher amplitude oscillations than the suprachiasmatic nucleus (SCN), suggested that it might be an alternative to the master clock to control the circadian rhythm . Although we have demonstrated that CP holds a functional circadian clock, the ability of the CP to synthesize melatonin has not been studied.…”

“…We were surprised with this result. Given the fact that CP harbors a robust circadian clock and taking into consideration its privileged localization in brain ventricles, a possible contribution to CSF melatonin circadian rhythm would be expected. Nevertheless, our findings agree with previous data pointing that circadian variations are not common in extrapineal melatonin sources, with the exception of the retina .…”