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Nucleus Accumbens D1 Receptor-Expressing Spiny Projection Neurons Control Food Motivation and Obesity
Bridget A Matikainen-Ankney1, Alex A Legaria2, Yiyan Pan1
1Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri.
Biological Psychiatry
|December 9, 2022
Summary
Obese mice show increased motivation for food, driven by enhanced activity in nucleus accumbens D1 neurons. Blocking these neurons reduced food seeking and weight gain, highlighting them as a potential obesity treatment target.
Area of Science:
- Neuroscience
- Obesity Research
- Behavioral Science
Background:
- Obesity is a chronic disorder linked to altered food motivation.
- Brain circuits controlling food motivation in obesity are not fully understood.
- Investigating neural mechanisms of altered food motivation in obesity is crucial.
Purpose of the Study:
- To test if nucleus accumbens (NAc) circuits promoting appetitive behavior are enhanced in obesity.
- To investigate the role of specific NAc neurons in food motivation and diet-induced obesity.
Main Methods:
- Utilized a novel behavioral assay to quantify work during food seeking.
- Performed in vivo and ex vivo cell-specific recordings.
- Employed synaptic blocking techniques to assess neuronal necessity.
Main Results:
- Obese mice exhibited increased work for food, indicating heightened motivation.
- D1 receptor-expressing NAc spiny projection neurons (D1SPNs) showed greater activation during food seeking in obese mice.
- Enhanced intrinsic excitability and excitatory drive onto D1SPNs were observed in obese mice.
- Blocking D1SPN synaptic transmission reduced work for food and attenuated weight gain.
Conclusions:
- NAc core D1SPNs are essential for food motivation.
- D1SPNs play a critical role in the development of diet-induced obesity.
- NAc core D1SPNs represent a potential therapeutic target for obesity prevention.
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