Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway
Abstract Impaired regulation of food intake underlies numerous health problems, including obesity and type 2 diabetes, yet how brain systems controlling reward seeking become dysregulated to promote overeating is unknown. Glutamatergic neurons of the lateral hypothalamic area (LHA) are thought to ac...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59686-2 |
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| author | Kuldeep Shrivastava Vikshar Athreya Yi Lu Jorge Luis-Islas Ashley Han Tess F. Kowalski Mark A. Rossi |
| author_facet | Kuldeep Shrivastava Vikshar Athreya Yi Lu Jorge Luis-Islas Ashley Han Tess F. Kowalski Mark A. Rossi |
| author_sort | Kuldeep Shrivastava |
| collection | DOAJ |
| description | Abstract Impaired regulation of food intake underlies numerous health problems, including obesity and type 2 diabetes, yet how brain systems controlling reward seeking become dysregulated to promote overeating is unknown. Glutamatergic neurons of the lateral hypothalamic area (LHA) are thought to act as a brake on feeding, which is dysregulated during diet-induced obesity. These neurons receive input from the extended amygdala, including the bed nucleus of the stria terminalis (BNST). However, the circuit mechanisms underlying the ability of this pathway to control feeding behavior and how they contribute to dysregulated eating are unclear. Here, we discover that BNST projections to LHA (BNST→LHA) promote reward seeking in an energy state-dependent manner by combining optogenetics, in vivo multiphoton calcium imaging, and electrophysiology in mice. Synaptic strength and neuronal function within the BNST→LHA pathway are dynamically regulated according to energy state to guide reward seeking. These findings suggest that hormonal factors modulate the function of the BNST→LHA pathway to align food seeking with current energy needs. |
| format | Article |
| id | doaj-art-14874f1a2dc949f59a78f6e499be1649 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-14874f1a2dc949f59a78f6e499be16492025-08-20T01:51:30ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59686-2Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathwayKuldeep Shrivastava0Vikshar Athreya1Yi Lu2Jorge Luis-Islas3Ashley Han4Tess F. Kowalski5Mark A. Rossi6Center for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical SchoolCenter for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical SchoolCenter for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical SchoolCenter for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical SchoolCenter for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical SchoolCenter for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical SchoolCenter for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical SchoolAbstract Impaired regulation of food intake underlies numerous health problems, including obesity and type 2 diabetes, yet how brain systems controlling reward seeking become dysregulated to promote overeating is unknown. Glutamatergic neurons of the lateral hypothalamic area (LHA) are thought to act as a brake on feeding, which is dysregulated during diet-induced obesity. These neurons receive input from the extended amygdala, including the bed nucleus of the stria terminalis (BNST). However, the circuit mechanisms underlying the ability of this pathway to control feeding behavior and how they contribute to dysregulated eating are unclear. Here, we discover that BNST projections to LHA (BNST→LHA) promote reward seeking in an energy state-dependent manner by combining optogenetics, in vivo multiphoton calcium imaging, and electrophysiology in mice. Synaptic strength and neuronal function within the BNST→LHA pathway are dynamically regulated according to energy state to guide reward seeking. These findings suggest that hormonal factors modulate the function of the BNST→LHA pathway to align food seeking with current energy needs.https://doi.org/10.1038/s41467-025-59686-2 |
| spellingShingle | Kuldeep Shrivastava Vikshar Athreya Yi Lu Jorge Luis-Islas Ashley Han Tess F. Kowalski Mark A. Rossi Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway Nature Communications |
| title | Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway |
| title_full | Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway |
| title_fullStr | Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway |
| title_full_unstemmed | Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway |
| title_short | Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway |
| title_sort | energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway |
| url | https://doi.org/10.1038/s41467-025-59686-2 |
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