Intrinsic circadian timekeeping properties of the thalamic lateral geniculate nucleus

Abstract

Circadian rhythmicity in mammals is sustained by the central brain clock - the suprachiasmatic nucleus of the hypothalamus (SCN), entrained to the ambient light-dark conditions through a dense retinal input. However, recent discoveries of autonomous clock gene expression cast doubt on the supremacy of the SCN and suggest circadian timekeeping mechanisms devolve to local brain clocks. Here we use a combination of molecular, electrophysiological and optogenetic tools to evaluate intrinsic clock properties of the main retinorecipient thalamic centre - the lateral geniculate nucleus (LGN). We identify the dorsolateral geniculate nucleus (DLG) as a slave oscillator, which exhibits core clock gene expression exclusively in vivo. Additionally, we provide compelling evidence for intrinsic clock gene expression accompanied by circadian variation in neuronal activity in the intergeniculate leaflet (IGL) and ventrolateral geniculate nucleus (VLG). Finally, our optogenetic experiments propose the VLG as a light-entrainable oscillator, whose phase may be advanced by retinal input at the beginning of the projected night. Altogether, this study for the first time demonstrates autonomous timekeeping mechanisms shaping circadian physiology of the LGN.