Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons

Oct 7, 2009Proceedings of the National Academy of Sciences of the United States of America

Natural, unpredictable daily rhythms created by specific mammal brain cells

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Fully isolated SCN neurons can sustain circadian cycling for at least 1 week.

Circadian rhythms in SCN neurons are generated intrinsically but may be unstable.
Around 80% of recorded neurons exhibited arrhythmic behavior while still expressing neuropeptides AVP and VIP.
Neurons gained or lost circadian rhythmicity spontaneously and in response to forskolin stimulation.
In SCN explants with blocked spike-dependent signaling, neurons also demonstrated changes in circadian cycling over days.
The accumulation rate of PERIOD2 protein could predict the spontaneous onset of arrhythmicity.

AI simplified

Circadian rhythms are modeled as reliable and self-sustained oscillations generated by single cells. The mammalian suprachiasmatic nucleus (SCN) keeps near 24-h time in vivo and in vitro, but the identity of the individual cellular pacemakers is unknown. We tested the hypothesis that circadian cycling is intrinsic to a unique class of SCN neurons by measuring firing rate or Period2 gene expression in single neurons. We found that fully isolated SCN neurons can sustain circadian cycling for at least 1 week. Plating SCN neurons at <100 cells/mm(2) eliminated synaptic inputs and revealed circadian neurons that contained arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) or neither. Surprisingly, arrhythmic neurons (nearly 80% of recorded neurons) also expressed these neuropeptides. Furthermore, neurons were observed to lose or gain circadian rhythmicity in these dispersed cell cultures, both spontaneously and in response to forskolin stimulation. In SCN explants treated with tetrodotoxin to block spike-dependent signaling, neurons gained or lost circadian cycling over many days. The rate of PERIOD2 protein accumulation on the previous cycle reliably predicted the spontaneous onset of arrhythmicity. We conclude that individual SCN neurons can generate circadian oscillations; however, there is no evidence for a specialized or anatomically localized class of cell-autonomous pacemakers. Instead, these results indicate that AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling.

Full Text

Full text is available at the source.

View full text ↗

Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons

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