Discrete prefrontal neuronal circuits determine repeated stress-induced behavioral phenotypes in male mice.
Neuron
; 112(5): 786-804.e8, 2024 Mar 06.
Article
em En
| MEDLINE
| ID: mdl-38228137
ABSTRACT
Chronic stress is a major risk factor for psychiatric disorders, including depression. Although depression is a highly heterogeneous syndrome, it remains unclear how chronic stress drives individual differences in behavioral responses. In this study, we developed a subtyping-based approach wherein stressed male mice were divided into four subtypes based on their behavioral patterns of social interaction deficits and anhedonia, the core symptoms of psychiatric disorders. We identified three prefrontal cortical neuronal projections that regulate repeated stress-induced behavioral phenotypes. Among them, the medial prefrontal cortex (mPFC)âanterior paraventricular thalamus (aPVT) pathway determines the specific behavioral subtype that exhibits both social deficits and anhedonia. Additionally, we identified the circuit-level molecular mechanism underlying this subtype KDM5C-mediated epigenetic repression of Shisa2 transcription in aPVT projectors in the mPFC led to social deficits and anhedonia. Thus, we provide a set of biological aspects at the cellular, molecular, and epigenetic levels that determine distinctive stress-induced behavioral phenotypes.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anedonia
/
Transtornos Mentais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article