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Hippocampus ghrelin signaling mediates appetite through lateral hypothalamic orexin pathways
Ted M Hsu1,2, Joel D Hahn3, Vaibhav R Konanur1
1Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, United States.
Elife
|January 9, 2016
Summary
Ghrelin, a gut hormone, signals to the ventral hippocampus (vHP) to stimulate appetite based on learned cues, not just hunger. This pathway involves the lateral hypothalamus (LHA) and orexin signaling, revealing new appetite regulation mechanisms.
Area of Science:
- Neurobiology
- Endocrinology
- Appetite Regulation
Background:
- Most feeding research focuses on metabolic needs, neglecting habitual feeding patterns.
- Learned and environmental factors significantly influence meal timing and consumption.
- The role of gut hormones in non-homeostatic feeding is not fully understood.
Purpose of the Study:
- To investigate the neural pathways linking gut hormones to learned feeding behaviors.
- To explore the role of ghrelin in conditioned appetite.
- To identify downstream targets of ghrelin signaling in the brain.
Main Methods:
- Investigated the communication between ghrelin, ventral hippocampus (vHP), and lateral hypothalamus (LHA) neurons.
- Examined the role of orexin signaling in ghrelin-mediated feeding.
- Utilized neurobiological techniques to map neural circuits.
Main Results:
- Ghrelin stimulates meal-entrained conditioned appetite via ventral hippocampus (vHP) neurons.
- The lateral hypothalamus (LHA) is a critical downstream pathway for vHP ghrelin effects.
- vHP ghrelin-activated neurons directly signal to orexin-expressing neurons in the LHA.
- Orexin-1 receptor activation is essential for ghrelin-induced hyperphagia.
Conclusions:
- Discovered a novel neural system where ghrelin in the hippocampus engages LHA orexin signaling.
- This circuitry regulates higher-order aspects of feeding, including conditioned appetite.
- Findings challenge the metabolic deficit-centric view of feeding control.
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