| Autor: |
Kielhold ML, Jacobs DS, Torrado-Pacheco A, Lebowitz JJ, Langdon AJ, Williams JT, Zweifel LS, Moghaddam B |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 28. Date of Electronic Publication: 2024 Oct 28. |
| DOI: |
10.1101/2024.10.28.620713 |
| Abstrakt: |
Psychosis is a hallmark of schizophrenia. It typically emerges in late adolescence and is associated with dopamine abnormalities and aberrant salience. Most genes associated with schizophrenia risk involve ubiquitous targets that may not explain delayed emergence of dopaminergic disruptions. This includes GRIN2A, the gene encoding the GluN2A subunit of the NMDA receptor. Both common and rare variants of GRIN2A are considered genetic risk factors for schizophrenia diagnosis. We find that Grin2a knockout in dopamine neurons during adolescence is sufficient to produce a behavioral phenotype that mirrors aspects of psychosis. These include disruptions in effort optimization, salience attribution, and ability to utilize feedback to guide behavior. We also find a selective effect of this manipulation on dopamine release during prediction error signaling. These data provide mechanistic insight into how variants of GRIN2A may lead to the latent presentation of aberrant salience and abnormalities in dopamine dynamics. This etiologically relevant model may aid future discovery of course altering treatments for schizophrenia. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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