ArticleBiological psychiatry2024
Manipulating ΔFOSB in D1-Type Medium Spiny Neurons of the Nucleus Accumbens Reshapes Whole-Brain Functional Connectivity.
Article in Biological psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 6 citations in OpenAlex.
- Brain-wide induction of ΔFOSB and altered co-activation networks in a rat model for exercise training.Translational psychiatry · 2026Article
- Robust automated preclinical fMRI preprocessing via a multi-stage dilated convolutional Swin Transformer affine registration.Frontiers in neuroscience · 2025Article
- Chronic Morphine Leaves a Durable Fingerprint on Whole-Brain Functional Connectivity.Biological psychiatry · 2024Article
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11 authors at 4 institutions in 4 countries.
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Abstract
backgroundThe transcription factor ΔFOSB, acting in the nucleus accumbens, has been shown to control transcriptional and behavioral responses to opioids and other drugs of abuse. However, circuit-level consequences of ΔFOSB induction on the rest of the brain, which are required for its regulation of complex behavior, remain unknown.
methodsWe used an epigenetic approach in mice to suppress or activate the endogenous Fosb gene and thereby decrease or increase, respectively, levels of ΔFOSB selectively in D1-type medium spiny neurons of the nucleus accumbens and tested whether these modifications affect the organization of functional connectivity (FC) in the brain. We acquired functional magnetic resonance imaging data at rest and in response to a morphine challenge and analyzed both stationary and dynamic FC patterns.
resultsThe 2 manipulations modified brainwide communication markedly and differently. ΔFOSB down- and upregulation had overlapping effects on prefrontal- and retrosplenial cortex-centered networks, but also generated specific FC signatures for epithalamus (habenula) and dopaminergic/serotonergic centers, respectively. Analysis of dynamic FC patterns showed that increasing ΔFOSB essentially altered responsivity to morphine and uncovered striking modifications of the roles of the epithalamus and amygdala in brain communication, particularly upon ΔFOSB downregulation.
conclusionsThese novel findings illustrate how it is possible to link activity of a transcription factor within a single cell type of an identified brain region to consequent changes in circuit function brainwide by use of functional magnetic resonance imaging, and they pave the way for fundamental advances in bridging the gap between transcriptional and brain connectivity mechanisms underlying opioid addiction.
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