Orexin deficiency modulates cognitive flexibility in a sex-dependent manner.
animal models of schizophrenia
anxiety
attentional set shifting
cognitive flexibility
food consumption
learning and memory
narcolepsy
neuropeptides
orexin
transgenic mice
Journal
Genes, brain, and behavior
ISSN: 1601-183X
Titre abrégé: Genes Brain Behav
Pays: England
ID NLM: 101129617
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
28
05
2020
revised:
01
10
2020
accepted:
14
10
2020
pubmed:
19
10
2020
medline:
15
2
2022
entrez:
18
10
2020
Statut:
ppublish
Résumé
Cognitive flexibility is an important executive function and refers to the ability to adapt behaviors in response to changes in the environment. Of note, many brain disorders are associated with impairments in cognitive flexibility. Several classical neurotransmitter systems including dopamine, acetylcholine and noradrenaline are shown to be important for cognitive flexibility, however, there is not much known about the role of neuropeptides. The neuropeptide orexin, which is brain-widely released by neurons in the lateral hypothalamus, is a major player in maintaining sleep/wake cycle, feeding behavior, arousal, and motivational behavior. Recent studies showed a role of orexin in attention, cognition and stress-induced attenuation of cognitive flexibility by disrupting orexin signaling locally or systemically. However, it is not known so far whether brain-wide reduction or loss of orexin affects cognitive flexibility. We investigated this question by testing male and female orexin-deficient mice in the attentional set shifting task (ASST), an established paradigm of cognitive flexibility. We found that orexin deficiency impaired the intra-dimensional shift phase of the ASST selectively in female homozygous orexin-deficient mice and improved the first reversal learning phase selectively in male homozygous orexin-deficient mice. We also found that these orexin-mediated sex-based modulations of cognitive flexibility were not correlated with trait anxiety, narcoleptic episodes, and reward consumption. Our findings highlight a sexually dimorphic role of orexin in regulating cognitive flexibility and the need for further investigations of sex-specific functions of the orexin circuitry.
Substances chimiques
Hcrt protein, mouse
0
Orexins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12707Informations de copyright
© 2020 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.
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