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Neuropeptide Y co-opts neuronal ensembles for memory lability and stability
Yan-Jiao Wu1,2,3, Xue Gu2,4, Yalei Kong1,2
1Department of Anesthesiology, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders (LEAD), Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature Neuroscience
|April 1, 2026
Summary
Neuropeptide Y (NPY)-expressing interneurons in the ventral CA1 region of the brain control memory extinction. These neurons use fast and slow inhibition to regulate memory stability and lability.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- Memory engrams involve excitatory neurons, while inhibitory neurons control memory persistence.
- The specific roles of interneuron subtypes in memory fate remain unclear.
Purpose of the Study:
- Investigate the role of specific interneurons in determining memory lability and stability.
- Elucidate the mechanisms by which interneurons influence memory extinction.
Main Methods:
- Used male mice undergoing cued fear memory training and extinction.
- Monitored calcium dynamics and neuropeptide Y (NPY) release in ventral CA1 (vCA1) interneurons.
- Examined the necessity and sufficiency of NPY in memory extinction.
Main Results:
- NPY-expressing GABA-ergic interneurons in vCA1 facilitate memory acquisition and extinction.
- NPY release and interneuron activity increase during extinction learning.
- NPY acts on distinct neuronal ensembles to gate early and late stages of extinction.
Conclusions:
- Subtype-specific, slow peptidergic inhibition from interneurons regulates engram lability versus stability.
- NPY-expressing interneurons play a dual role in memory processing.
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