Circadian oscillators in the epithalamus

Abstract

The habenula complex is implicated in a range of cognitive, emotional and reproductive behaviors, and recently this epithalamic structure was suggested to be a component of the brain's circadian system. Circadian timekeeping is driven in cells by the cyclical activity of core clock genes and proteins such as per2/PER2. There are currently no reports of rhythmic clock gene/protein expression in the habenula and therefore the question of whether this structure has an intrinsic molecular clock remains unresolved. Here, using videomicroscopy imaging and photon-counting of a PER2::luciferase (LUC) fusion protein together with multiunit electrophysiological recordings, we tested the endogenous circadian properties of the mouse habenula in vitro. We show that a circadian oscillator is localized primarily to the medial portion of the lateral habenula. Rhythms in PER2:: LUC bioluminescence here are visualized in single cells and oscillations continue in the presence of the sodium channel blocker, tetrodotoxin, indicating that individual cells have intrinsic timekeeping properties. Ependymal cells lining the dorsal third ventricle also express circadian oscillations of PER2. These findings establish that neurons and non-neuronal cells in the epithalamus express rhythms in cellular and molecular activities, indicating a role for circadian oscillators in the temporal regulation of habenula controlled processes and behavior.

Breaking symmetry: The zebrafish as a model for understanding left‐right asymmetry in the developing brain

“…Based on S-antigen immuno-reactivity (S-antigen is a specific marker for retinal and pineal photoreceptors and considered to be a marker of photoreceptor differentiation), pinealocyte-like cells have been observed in both the pineal and the medial habenular sub-nucleus of the hamster (Korf et al, 1986) and mouse (Korf et al, 1990). The proposed role of the habenulae in the regulation of circadian rhythms further supports the intimate link between the photoreceptive pineal complex and the habenulae (Guilding et al, 2010).…”

Anatomical distribution and daily profile ofgper1bgene expression in brain and peripheral structures of goldfish (Carassius auratus)

“…Present results in goldfish confirm a relevant presence of clock genes (gper1b) in the habenula of fish. These nuclei have been demonstrated to have circadian firing rhythms and photic responsiveness in rodents (Zhao & Rusak, 2005), to show clock genes rhythmicity (Guilding et al, 2010) and to be connected directly to the retina and the SCN in mammals (Qu et al, 1996).…”

The role of lateral habenula–dorsal raphe nucleus circuits in higher brain functions and psychiatric illness

“…A few other brain regions have also been shown to have the independent capacity to generate circadian rhythms independently of the SCN pacemaker [90]. The best-studied of these regions are the olfactory bulbs [91] and retina [92], but the Hb, and particularly the LHb, has also been shown to generate circadian firing-rate rhythms for at least a few cycles in vitro, and to generate circadian rhythms of clock gene expression [93,94]. The LHb is further linked to the circadian system because it receives a vasopressin-containing projection from the SCN, which plays an important role in conveying circadian information [95,96], and cells in the LHb respond to light input similarly to SCN neurons [93].…”