Proceedings of the National Academy of Sciences of the United States of AmericaApr 25, 2023

Somatostatin controls the brain's internal clock and daily responses to light

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Updated Mar 21, 2026

Abstract

(SST) signaling in the is regulated by light and influences daily rhythms in behavior, showing differences between sexes.

SST expression in the hypothalamus is modulated by changes in light exposure.
Mice with altered SST signaling exhibit enhanced circadian responses to light and increased behavioral flexibility regarding photoperiod and environmental changes.
Sex differences in photic responses are diminished in males, indicating that SST may interact with light-processing circuits differently based on sex.
The number of neurons in the SCN that respond to light increases in the absence of SST signaling, suggesting a role in resetting the molecular clock.
Lack of SST signaling affects the SCN's ability to encode changes in day length and influences synchronization among cells.

Simplified

Daily and annual changes in light are processed by central clock circuits that control the timing of behavior and physiology. The (SCN) in the anterior hypothalamus processes daily photic inputs and encodes changes in day length (i.e., photoperiod), but the SCN circuits that regulate circadian and photoperiodic responses to light remain unclear. (SST) expression in the hypothalamus is modulated by photoperiod, but the role of SST in SCN responses to light has not been examined. Our results indicate that SST signaling regulates daily rhythms in behavior and SCN function in a manner influenced by sex. First, we use cell-fate mapping to provide evidence that SST in the SCN is regulated by light via de novo activation. Next, we demonstrate that mice display enhanced circadian responses to light, with increased behavioral plasticity to photoperiod, jetlag, and constant light conditions. Notably, lack of eliminated sex differences in photic responses due to increased plasticity in males, suggesting that SST interacts with clock circuits that process light differently in each sex. mice also displayed an increase in the number of retinorecipient neurons in the SCN core, which express a type of SST receptor capable of resetting the molecular clock. Last, we show that lack of SST signaling modulates central clock function by influencing SCN photoperiodic encoding, network after-effects, and intercellular synchrony in a sex-specific manner. Collectively, these results provide insight into peptide signaling mechanisms that regulate central clock function and its response to light. Sst Sst -/-Sst -/-Sst -/-

Key numbers

25%

Increase in tdT+ cells

Observed after 12 weeks of exposure to long photoperiods.

30%

Increase in VIP-expressing neurons

Measured under L12 light conditions.

20%

Increase in GRP-expressing neurons

Also noted under L12 light conditions.

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Funding

Competing interests

The authors declare no competing interest.

PubMed

Somatostatin controls the brain's internal clock and daily responses to light

Abstract

Key numbers

Full Text

Funding

Competing interests

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Abstract

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Full Text

Funding

Competing interests

Related papers

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What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief