Conditioned place avoidance is associated with a distinct hippocampal phenotype, partly preserved pattern separation, and reduced reactive oxygen species production after stress.
Genes Brain Behav
; 22(2): e12840, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36807494
ABSTRACT
Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated context (Avoiders), or do not (Non-Avoiders). Weighted genome correlational network analysis showed that increased expression of oxidative phosphorylation-associated gene transcripts and decreased expression of gene transcripts for axon guidance and insulin signaling were associated with avoidance behavior. Based on these data, in Experiment 2, we hypothesized that Avoiders would exhibit elevated hippocampal (HPC) ROS production and degraded object pattern separation (OPS) compared with Nonavoiders. Stress impaired pattern separation performance in Non-Avoider and Avoider rats compared with nonstressed Controls, but surprisingly, Avoiders exhibited partly preserved pattern separation performance and significantly lower ROS production compared with Non-Avoiders. Lower ROS production was associated with better OPS performance in Stressed rats, but ROS production was not associated with OPS performance in Controls. These results suggest a strong negative association between HPC ROS production and pattern separation after stress, and that stress effects on these outcome variables may be associated with avoidance of a stress-paired context.
Palavras-chave
DG-CA3; RNA sequencing (RNAseq); conditioned place avoidance (CPA); dentate gyrus; differentially expressed genes (DEGs); dorsal hippocampus; electron paramagnetic resonance spectroscopy (EPR); electron spin resonance spectroscopy (ESR); hippocampus (HPC); maximal respiratory capacity; metabolism; mitochondria; mitochondrial spare respiratory capacity; object pattern separation (OPS); oxygen consumption rate (OCR); predator odor; reactive oxygen species (ROS); seahorse extracellular flux analysis (SEFA); stress; weighted genome correlational network analysis (WGCNA)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos de Estresse Pós-Traumáticos
/
Hipocampo
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Genes Brain Behav
Assunto da revista:
CIENCIAS DO COMPORTAMENTO
/
GENETICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos