Related Experiment Video
Updated: Jun 5, 2026
09:29
Isolation of Targeted Hypothalamic Neurons for Studies of Hormonal, Metabolic, and Electrical Regulation
Published on: August 4, 2023
A hypothalamic circuit for anticipating future changes in energy balance.
Samuel J Walker1, Elijah D Lowenstein1, Amelia M Douglass1
1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Neuron
|June 3, 2026
Summary
The brain
Area of Science:
- Neuroscience
- Metabolism
- Behavioral Biology
Background:
- AgRP neurons drive hunger and food seeking, typically activated by low energy stores.
- Environmental cues can inhibit AgRP neurons, but their role in activation is unclear.
Purpose of the Study:
- To investigate if predictions of future fasting can rapidly activate AgRP neurons.
- To identify the neural circuits mediating this activation.
Main Methods:
- Utilized mouse models to study neural circuit activity.
- Investigated the role of paraventricular hypothalamic (PVH) neurons expressing Sim2 (PVHSim2).
- Examined the effects of chronic silencing of PVHSim2 neurons.
Main Results:
- Demonstrated rapid activation of AgRP neurons by predicted future fasting in mice.
- Identified excitatory input from PVHSim2 neurons as the driver of this activation.
- Showed that PVHSim2 neurons are sensitive to predictions of future energy states.
- Chronic silencing of PVHSim2 neurons led to persistent hypophagia (reduced appetite).
Conclusions:
- Cognitively processed contextual information via PVHSim2 neurons strongly activates AgRP neurons.
- The PVHSim2-to-AgRP-neuron circuit anticipates and prevents negative energy balance.
- This circuit offers a novel dimension to hunger regulation by predicting future energy states.
Keywords:
AGRP neuronsappetiteenergy balancefeedingfood intakehomeostasishungerhypothalamusmetabolismneuroscienceMore Related Videos
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