Orexin neurons and inhibitory Agrp→orexin circuits guide spatial exploration in mice.
Agrp
behaviour
electrophysiology
exploration
hypothalamus
optogenetics
orexin
Journal
The Journal of physiology
ISSN: 1469-7793
Titre abrégé: J Physiol
Pays: England
ID NLM: 0266262
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
13
05
2020
accepted:
13
07
2020
pubmed:
16
7
2020
medline:
16
2
2021
entrez:
16
7
2020
Statut:
ppublish
Résumé
Photoinhibition of endogenous activity of lateral hypothalamic orexin neurons causes place preference and reduces innate avoidance Endogenous activity of orexin neurons correlates with place preference Mediobasal hypothalamic Agrp neurons inhibit orexin neurons via GABA, and chemogenetic suppression of Agrp neurons increases avoidance in an orexin receptor-dependent manner. Hypothalamic orexin/hypocretin neurons integrate multiple sensory cues and project brain-wide to orchestrate diverse innate behaviours. Their loss impairs many context-appropriate actions, but the motivational characteristics of orexin cell activity remain unclear. We and others previously approached this question by artificial orexin stimulation, which could induce either rewarding (positive valence) or aversive (negative valence) brain activity. It is unknown to what extent such approaches replicate natural/endogenous orexin signals, which rapidly fluctuate during wakefulness. Here we took an alternative approach, focusing on observing and silencing natural orexin cell signals associated with a fundamental innate behaviour, self-paced spatial exploration. We found that mice are more likely to stay in places paired with orexin cell optosilencing. The orexin cell optosilencing also reduced avoidance of places that mice find innately aversive. Correspondingly, calcium recordings revealed that orexin cell activity rapidly reduced upon exiting the innately aversive places. Furthermore, we provide optogenetic evidence for an inhibitory GABAergic Agrp→orexin hypothalamic neurocircuit, and find that Agrp cell suppression increases innate avoidance behaviour, consistent with orexin disinhibition. These results imply that exploration may be motivated and oriented by a need to reduce aversive orexin cell activity, and suggest a hypothalamic circuit for fine-tuning orexin signals to changing ethological priorities.
Substances chimiques
Agouti-Related Protein
0
Orexins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4371-4383Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC10055
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC10055
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
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