GHS-R1a signaling drives anxiety-related behavior by shaping excitability of ventromedial hypothalamic neurons
Abstract The neural substrates of anxiety are poorly understood, which hinders treatment of anxiety disorders. Here we found, αCaMKII+ neurons in the ventral medial hypothalamic nucleus (VMH) responded to stressors with increased activity in male mice, both under physiological conditions and after r...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59116-3 |
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| Summary: | Abstract The neural substrates of anxiety are poorly understood, which hinders treatment of anxiety disorders. Here we found, αCaMKII+ neurons in the ventral medial hypothalamic nucleus (VMH) responded to stressors with increased activity in male mice, both under physiological conditions and after repeated restraint stress. Activation of VMH αCaMKII+ neurons were necessary and sufficient to ameliorate stress-induced anxiety. The peripheral metabolic hormone ghrelin and receptor GHS-R1a play a complex role in emotion regulation; however, the mechanism is uncertain. A delayed increase in GHS-R1a expression in VMH αCaMKII+ neurons coincided with the development of stress-induced enhancement of anxiety-related behavior. GHS-R1a expression in VMH αCaMKII+ neurons promoted anxiety-related behavior, whereas GHS-R1a knockdown had the opposite effect. GHS-R1a upregulation inhibited the excitability of VMH αCaMKII+ neurons. We conclude that GHSR1a signaling drives stress-induced anxiety by shaping the activity of VMH αCaMKII+ neurons. GHS-R1a may be a therapeutic target for treating anxiety disorders such as post-traumatic stress disorder. |
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| ISSN: | 2041-1723 |