eprintid: 10201370 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/20/13/70 datestamp: 2024-12-11 08:04:37 lastmod: 2024-12-11 08:04:37 status_changed: 2024-12-11 08:04:37 type: article metadata_visibility: show sword_depositor: 699 creators_name: Holt, Marie K creators_name: Valderrama, Natalia creators_name: Polanco, Maria J creators_name: Hayter, Imogen creators_name: Badenoch, Ellena G creators_name: Trapp, Stefan creators_name: Rinaman, Linda title: Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G02 keywords: Glucagon-like peptide-1; Acute stress; Nucleus of the solitary tract; Corticotropin releasing hormone; Appetite; Anxiety-like behaviour note: Copyright © 2024 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: 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. date: 2025-01 date_type: published publisher: Elsevier BV official_url: https://doi.org/10.1016/j.molmet.2024.102076 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2341731 doi: 10.1016/j.molmet.2024.102076 pii: S2212-8778(24)00207-2 lyricists_name: Trapp, Stefan lyricists_id: STRAP42 actors_name: Trapp, Stefan actors_id: STRAP42 actors_role: owner full_text_status: public publication: Molecular Metabolism volume: 91 article_number: 102076 event_location: Germany issn: 2212-8778 citation: Holt, Marie K; Valderrama, Natalia; Polanco, Maria J; Hayter, Imogen; Badenoch, Ellena G; Trapp, Stefan; Rinaman, Linda; (2025) Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract. Molecular Metabolism , 91 , Article 102076. 10.1016/j.molmet.2024.102076 <https://doi.org/10.1016/j.molmet.2024.102076>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10201370/1/1-s2.0-S2212877824002072-main%20%281%29.pdf