Temporally chimeric mice reveal flexibility of circadian period-setting in the suprachiasmatic nucleus

Mar 12, 2016Proceedings of the National Academy of Sciences of the United States of America

Mice with mixed internal clocks show flexible timing control in the brain's daily rhythm center

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Chimeric mice with dopamine 1a receptor (Drd1a) cells and 20-h clock cells exhibit robust circadian clocks.

The suprachiasmatic nucleus (SCN) controls daily behavior through interactions between individual cell clocks and circuit-level properties.
Chimeric circuits composed of different cell types can maintain a coherent wave of gene expression similar to nonchimeric SCN.
The interaction between 24-h Drd1a and 20-h non-Drd1a neurons influences the overall ensemble period of the circadian clock.
Exposure to different light cycles can switch the dominant influence of the cell types on the ensemble period.
Chimeric circuits demonstrate resilience and plasticity in circadian timing, suggesting new principles of SCN operation.

AI simplified

The suprachiasmatic nucleus (SCN) is the master circadian clock controlling daily behavior in mammals. It consists of a heterogeneous network of neurons, in which cell-autonomous molecular feedback loops determine the period and amplitude of circadian oscillations of individual cells. In contrast, circuit-level properties of coherence, synchrony, and ensemble period are determined by intercellular signals and are embodied in a circadian wave of gene expression that progresses daily across the SCN. How cell-autonomous and circuit-level mechanisms interact in timekeeping is poorly understood. To explore this interaction, we used intersectional genetics to create temporally chimeric mice with SCN containing dopamine 1a receptor (Drd1a) cells with an intrinsic period of 24 h alongside non-Drd1a cells with 20-h clocks. Recording of circadian behavior in vivo alongside cellular molecular pacemaking in SCN slices in vitro demonstrated that such chimeric circuits form robust and resilient circadian clocks. It also showed that the computation of ensemble period is nonlinear. Moreover, the chimeric circuit sustained a wave of gene expression comparable to that of nonchimeric SCN, demonstrating that this circuit-level property is independent of differences in cell-intrinsic periods. The relative dominance of 24-h Drd1a and 20-h non-Drd1a neurons in setting ensemble period could be switched by exposure to resonant or nonresonant 24-h or 20-h lighting cycles. The chimeric circuit therefore reveals unanticipated principles of circuit-level operation underlying the emergent plasticity, resilience, and robustness of the SCN clock. The spontaneous and light-driven flexibility of period observed in chimeric mice provides a new perspective on the concept of SCN pacemaker cells.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text ↗

Temporally chimeric mice reveal flexibility of circadian period-setting in the suprachiasmatic nucleus

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief