ArticleeLife2023
NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia-like behavior and reductions in excitatory synapses.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- The mPFC-reuniens-hippocampus pathway links brain circuitry and neural plasticity in antidepressant response.Nature communications · 2026Article
- Cocaine Hijacks the Npas4-dependent Somatostatin Ensembles in the mPFC to Mediate Attention.Neuroscience bulletin · 2026Article
- Maternal Isocaloric Monosaccharide Diets Reorganize Dorsal-Ventral Hippocampal Maturation and Ventral Plasticity in Rat Offspring.Cellular and molecular neurobiology · 2026Article
- Disruption of psychostimulant-associated memories by single, low dose ketamine in rats.Neuropharmacology · 2026Article
- The longitudinal relationships between parent-child alienation and depression in adolescents: insights of network analysis.Child and adolescent psychiatry and mental health · 2026Article
- Effects of Stress Coping Styles and Social Defeat on Zebrafish Behaviour and Brain Transcriptomics.Neuroscience bulletin · 2026Article
- Copper deficiency impairs oligodendrocyte maturation and social behavior via mitophagy and mTOR suppression in ASD.Science advances · 2026Article
- Integrative In Silico Analysis of miRNA-mRNA Regulatory Networks in the Prefrontal Cortex of Individuals with Psychiatric Disorders Who Died by Suicide.International journal of molecular sciences · 2026Article
- Disrupted synapses: prefrontal cortex-reward circuit dysfunction in stress-induced depression-like behaviors.Frontiers in cellular neuroscience · 2026Review
- Article
- Memory-Associated Immediate Early Genes: Roles in Synaptic Function, Memory Processes, and Neurological Diseases.Molecular neurobiology · 2025Review
- Single-cell transcriptomics reveals Sox6 positive interneurons enriched in the prefrontal cortex of female mice vulnerable to chronic social stress.Molecular psychiatry · 2025Article
- Data-Driven Analysis Identifies Novel Modulation of Social Behavior in Female Mice Witnessing Chronic Social Defeat Stress.Biological psychiatry · 2025Article
- Experience-induced NPAS4 reduces dendritic inhibition from CCK+ inhibitory neurons and enhances plasticity.Journal of neurophysiology · 2025Article
- A long noncoding eRNA forms R-loops to shape emotional experience-induced behavioral adaptation.Science (New York, N.Y.) · 2024Article
- Distinct transcriptional programs define a heterogeneous neuronal ensemble for social interaction.iScience · 2024Article
- Integration of whole-exome sequencing and structural neuroimaging analysis in major depressive disorder: a joint study.Translational psychiatry · 2024Article
- Ahnak in the prefrontal cortex mediates behavioral correlates of stress resilience and rapid antidepressant action in mice.Frontiers in molecular neuroscience · 2024Article
- Integrative transcriptome- and DNA methylation analysis of brain tissue from the temporal pole in suicide decedents and their controls.Molecular psychiatry · 2024Article
- Distinct transcriptional programs define a heterogeneous neuronal ensemble for social interaction.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
14 authors at 2 institutions in 1 country.
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Abstract
Chronic stress can produce reward system deficits (i.e., anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC). However, the molecular mechanisms by which chronic stress promotes depressive-like behavior and hypofrontality remain unclear. We show here that the neuronal activity-regulated transcription factor, NPAS4, in the mPFC is regulated by chronic social defeat stress (CSDS), and it is required in this brain region for CSDS-induced changes in sucrose preference and natural reward motivation in the mice. Interestingly, NPAS4 is not required for CSDS-induced social avoidance or anxiety-like behavior. We also find that mPFC NPAS4 is required for CSDS-induced reductions in pyramidal neuron dendritic spine density, excitatory synaptic transmission, and presynaptic function, revealing a relationship between perturbation in excitatory synaptic transmission and the expression of anhedonia-like behavior in the mice. Finally, analysis of the mice mPFC tissues revealed that NPAS4 regulates the expression of numerous genes linked to glutamatergic synapses and ribosomal function, the expression of upregulated genes in CSDS-susceptible animals, and differentially expressed genes in postmortem human brains of patients with common neuropsychiatric disorders, including depression. Together, our findings position NPAS4 as a key mediator of chronic stress-induced hypofrontal states and anhedonia-like behavior.
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