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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Funding: This work was financially supported by a project ‘Sonatina 2’ 2018/28/C/NZ4/00099 given to LC and ‘Preludium 14’ 2017/27/N/NZ4/00785 to KP from the Polish National Science Centre. KP was additionally supported by ‘Etiuda 8’ doctoral scholarship 2020/36/T/NZ4/00341. JM was supported by the Taiwan Ministry of Science and Technology (109-2320-B-038-020, 109-2314-B-038- 071, 109-2314-B-038-106-MY3, 108-2321-B-006-023-MY2, 107-2410-H-038-004-MY2), the Higher Education Sprout Project by the Taiwan Ministry of Education (DP2-109-21121-01-N-01, DP2-110- 21121-01-N-01), and Taipei Medical University (TMU107-AE1-B15, 107-3805-003-110, 107TMU-SHH-03).
Conflict of interest: The authors declare no competing financial interests.
Ethics approval: Experiments were approved by the Local (Krakow) Ethical Commission and performed in accordance with the European Community Council Directive of 24 November 1986 (86/0609/EEC) and the Polish Animal Welfare Act of 23 May 2012 (82/2012) and by the Institutional Animal Care and Use Committee of Taipei Medical University (IACUC Approval No: LAC-2019-0118).
Data availability: The data that support the findings of this study are available from the corresponding authors upon reasonable request.