Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract
Stress-induced behaviours are driven by complex neural circuits and some neuronal populations concurrently modulate diverse behavioural and physiological responses to stress. Glucagon-like peptide-1 (GLP-1)-producing preproglucagon (PPG) neurons within the lower brainstem caudal nucleus of the solit...
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Elsevier
2025-01-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877824002072 |
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| author | Marie K. Holt Natalia Valderrama Maria J. Polanco Imogen Hayter Ellena G. Badenoch Stefan Trapp Linda Rinaman |
| author_facet | Marie K. Holt Natalia Valderrama Maria J. Polanco Imogen Hayter Ellena G. Badenoch Stefan Trapp Linda Rinaman |
| author_sort | Marie K. Holt |
| collection | DOAJ |
| description | Stress-induced behaviours are driven by complex neural circuits and some neuronal populations concurrently modulate diverse behavioural and physiological responses to stress. Glucagon-like peptide-1 (GLP-1)-producing preproglucagon (PPG) neurons within the lower brainstem caudal nucleus of the solitary tract (cNTS) are particularly sensitive to stressful stimuli and are implicated in multiple physiological and behavioural responses to interoceptive and psychogenic threats. However, the afferent inputs driving stress-induced activation of PPG neurons are largely unknown, and the role of PPG neurons in anxiety-like behaviour is controversial. Through chemogenetic manipulations we reveal that cNTS PPG neurons have the ability to moderately increase anxiety-like behaviours in mice in a sex-dependent manner. Using an intersectional approach, we show that input from the paraventricular nucleus of the hypothalamus (PVN) drives activation of both the cNTS as a whole and PPG neurons in particular in response to acute restraint stress, but that while this input is rich in corticotropin-releasing hormone (CRH), PPG neurons do not express significant levels of receptors for CRH and are not activated following lateral ventricle delivery of CRH. Finally, we demonstrate that cNTS-projecting PVN neurons are necessary for the ability of restraint stress to suppress food intake in male mice. Our findings reveal sex differences in behavioural responses to PPG neural activation and highlight a hypothalamic-brainstem pathway in stress-induced hypophagia. |
| format | Article |
| id | doaj-art-8c386264c428488da1e1208b49a45885 |
| institution | Kabale University |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-8c386264c428488da1e1208b49a458852025-01-09T06:13:55ZengElsevierMolecular Metabolism2212-87782025-01-0191102076Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tractMarie K. Holt0Natalia Valderrama1Maria J. Polanco2Imogen Hayter3Ellena G. Badenoch4Stefan Trapp5Linda Rinaman6Florida State University, Department of Psychology and Program in Neuroscience, Tallahassee, FL, USA; Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK; University of Warwick, School of Life Sciences, Coventry, UK; Corresponding author. University of Warwick, School of Life Sciences, Gibbet Hill Road, CV4 7AL Coventry, UK.Florida State University, Department of Psychology and Program in Neuroscience, Tallahassee, FL, USAFlorida State University, Department of Psychology and Program in Neuroscience, Tallahassee, FL, USACentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK; GlaxoSmithKline Pharmaceuticals, London, UKUniversity of Warwick, School of Life Sciences, Coventry, UKCentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UKFlorida State University, Department of Psychology and Program in Neuroscience, Tallahassee, FL, USAStress-induced behaviours are driven by complex neural circuits and some neuronal populations concurrently modulate diverse behavioural and physiological responses to stress. Glucagon-like peptide-1 (GLP-1)-producing preproglucagon (PPG) neurons within the lower brainstem caudal nucleus of the solitary tract (cNTS) are particularly sensitive to stressful stimuli and are implicated in multiple physiological and behavioural responses to interoceptive and psychogenic threats. However, the afferent inputs driving stress-induced activation of PPG neurons are largely unknown, and the role of PPG neurons in anxiety-like behaviour is controversial. Through chemogenetic manipulations we reveal that cNTS PPG neurons have the ability to moderately increase anxiety-like behaviours in mice in a sex-dependent manner. Using an intersectional approach, we show that input from the paraventricular nucleus of the hypothalamus (PVN) drives activation of both the cNTS as a whole and PPG neurons in particular in response to acute restraint stress, but that while this input is rich in corticotropin-releasing hormone (CRH), PPG neurons do not express significant levels of receptors for CRH and are not activated following lateral ventricle delivery of CRH. Finally, we demonstrate that cNTS-projecting PVN neurons are necessary for the ability of restraint stress to suppress food intake in male mice. Our findings reveal sex differences in behavioural responses to PPG neural activation and highlight a hypothalamic-brainstem pathway in stress-induced hypophagia.http://www.sciencedirect.com/science/article/pii/S2212877824002072Glucagon-like peptide-1Acute stressNucleus of the solitary tractCorticotropin releasing hormoneAppetiteAnxiety-like behaviour |
| spellingShingle | Marie K. Holt Natalia Valderrama Maria J. Polanco Imogen Hayter Ellena G. Badenoch Stefan Trapp Linda Rinaman Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract Molecular Metabolism Glucagon-like peptide-1 Acute stress Nucleus of the solitary tract Corticotropin releasing hormone Appetite Anxiety-like behaviour |
| title | Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract |
| title_full | Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract |
| title_fullStr | Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract |
| title_full_unstemmed | Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract |
| title_short | Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract |
| title_sort | modulation of stress related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract |
| topic | Glucagon-like peptide-1 Acute stress Nucleus of the solitary tract Corticotropin releasing hormone Appetite Anxiety-like behaviour |
| url | http://www.sciencedirect.com/science/article/pii/S2212877824002072 |
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