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Updated: Sep 20, 2025
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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
Published on: December 12, 2019
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Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity
Shiyi Zhou1,2, Katherine E Novak1,2, Rachel Kaletsky1,2
1Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Nature Aging
|May 27, 2025
Summary
Body signals influence memory. Insulin signaling in the hypodermis regulates memory duration by activating neuronal Notch signaling and CREB, revealing a systemic link between metabolism and memory.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Memory regulation is primarily considered a neuronal process.
- The insulin/IGF-1-like signaling (IIS) pathway influences longevity, metabolism, and memory in C. elegans.
- Long-lived daf-2 mutants exhibit doubled memory duration, suggesting neuronal control.
Purpose of the Study:
- To investigate non-neuronal factors affecting memory regulation.
- To elucidate the systemic mechanisms connecting metabolism and memory.
- To explore the role of hypodermal signaling in memory.
Main Methods:
- Genetic manipulation of DAF-2 in Caenorhabditis elegans hypodermis.
- Analysis of OSM-11 ligand expression and Notch signaling activation in neurons.
- Single-nucleus RNA sequencing of neurons to assess gene expression.
- Assessment of memory and learning in aged animals.
Main Results:
- Hypodermal DAF-2 degradation significantly extends memory duration.
- This effect is mediated by the diffusible Notch ligand OSM-11 activating neuronal Notch signaling.
- Neuronal CREB and other memory gene expression increased.
- Hypodermal IIS-Notch pathway activation and OSM-11 overexpression rescue memory and learning in aged animals via CREB.
Conclusions:
- Insulin signaling in the hypodermis non-autonomously regulates neuronal memory.
- A systemic IIS-Notch-CREB signaling pathway connects body metabolism to neuronal function and memory.
- This pathway provides a mechanism for systemic regulation of memory and learning.
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