Intrinsic circadian timekeeping properties of the thalamic lateral geniculate nucleus

J Neurosci Res. 2021 Dec;99(12):3306-3324. doi: 10.1002/jnr.24973. Epub 2021 Nov 10.


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 center-the lateral geniculate nucleus (LGN) in male rats and mice. We identify the dorsolateral geniculate nucleus 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 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.

Keywords: PER2::LUC bioluminescence; RRID:IMSR_JAX:006852; circadian clock; clock genes; lateral geniculate nucleus; light-entrainable oscillator; multi-channel electrophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / physiology
  • Geniculate Bodies*
  • Hypothalamus
  • Male
  • Mammals
  • Mice
  • Neurons / metabolism
  • Rats
  • Suprachiasmatic Nucleus* / physiology