Postnatal Phencyclidine-Induced Deficits in Decision Making Are Ameliorated by Optogenetic Inhibition of Ventromedial Orbitofrontal Cortical Glutamate Neurons.
Learning rate
Optogenetics
Postnatal PCP
Probabilistic reversal learning
Schizophrenia
vmOFC
Journal
Biological psychiatry global open science
ISSN: 2667-1743
Titre abrégé: Biol Psychiatry Glob Open Sci
Pays: United States
ID NLM: 9918227369306676
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
received:
12
04
2023
revised:
12
07
2023
accepted:
01
08
2023
medline:
1
2
2024
pubmed:
1
2
2024
entrez:
1
2
2024
Statut:
epublish
Résumé
The orbitofrontal cortex (OFC) is essential for decision making, and functional disruptions within the OFC are evident in schizophrenia. Postnatal phencyclidine (PCP) administration in rats is a neurodevelopmental manipulation that induces schizophrenia-relevant cognitive impairments. We aimed to determine whether manipulating OFC glutamate cell activity could ameliorate postnatal PCP-induced deficits in decision making. Male and female Wistar rats ( Compared with saline-treated rats expressing YFP, PCP-treated rats expressing YFP completed fewer reversals, made fewer win-stay responses, and had lower learning rates. We induced similar performance impairments in saline-treated rats by activating vmOFC glutamate cells (ChR2). Strikingly, PCP-induced performance deficits were ameliorated when the activity of vmOFC glutamate cells was inhibited (halorhodopsin). Postnatal PCP-induced deficits in decision making are associated with hyperactivity of vmOFC glutamate cells. Thus, normalizing vmOFC activity may represent a potential therapeutic target for decision-making deficits in patients with schizophrenia.
Sections du résumé
Background
UNASSIGNED
The orbitofrontal cortex (OFC) is essential for decision making, and functional disruptions within the OFC are evident in schizophrenia. Postnatal phencyclidine (PCP) administration in rats is a neurodevelopmental manipulation that induces schizophrenia-relevant cognitive impairments. We aimed to determine whether manipulating OFC glutamate cell activity could ameliorate postnatal PCP-induced deficits in decision making.
Methods
UNASSIGNED
Male and female Wistar rats (
Results
UNASSIGNED
Compared with saline-treated rats expressing YFP, PCP-treated rats expressing YFP completed fewer reversals, made fewer win-stay responses, and had lower learning rates. We induced similar performance impairments in saline-treated rats by activating vmOFC glutamate cells (ChR2). Strikingly, PCP-induced performance deficits were ameliorated when the activity of vmOFC glutamate cells was inhibited (halorhodopsin).
Conclusions
UNASSIGNED
Postnatal PCP-induced deficits in decision making are associated with hyperactivity of vmOFC glutamate cells. Thus, normalizing vmOFC activity may represent a potential therapeutic target for decision-making deficits in patients with schizophrenia.
Identifiants
pubmed: 38298783
doi: 10.1016/j.bpsgos.2023.08.002
pii: S2667-1743(23)00091-5
pmc: PMC10829674
doi:
Types de publication
Journal Article
Langues
eng
Pagination
264-274Informations de copyright
© 2023 The Authors.