ArticleMolecular psychiatry2021
The impact of Semaphorin 4C/Plexin-B2 signaling on fear memory via remodeling of neuronal and synaptic morphology.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- A methylation study implicates the rewiring of brain neural circuits during puberty in the emergence of sex differences in depression symptoms.Journal of child psychology and psychiatry, and allied disciplines · 2022Pooled it
- Context-Dependent Roles of the Plexin-B Family Across Neurological, Oncological, Immune and Cardiovascular Disorders: Mechanisms and Therapeutic Implications.Life (Basel, Switzerland) · 2026Review
- Semaphorins and Their Role in Neuropathic Pain.Life (Basel, Switzerland) · 2026Review
- Proteomic profiling of brain organoids and extracellular vesicles identifies early Alzheimer's disease biomarkers and drug response heterogeneity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Acetate enhances long-term memory in female mice by sex-, context-, and brain region-specific epigenetic and transcriptional remodeling.Science signaling · 2026Article
- Beyond vessels: unraveling the impact of VEGFs on neuronal functions and structure.Journal of biomedical science · 2025Review
- [Neuronal plasticity changes in the central amygdala and prelimbic cortex network in mice with chronic unpredictable mild stress-induced depression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Dnmt3a1 regulates hippocampus-dependent memory via the downstream target Nrp1.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.Histology and histopathology · 2024Article
- VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites.Cellular and molecular life sciences : CMLS · 2024Article
- Evidence for common mechanisms of pathology between SHANK3 and other genes of Phelan-McDermid syndrome.Clinical genetics · 2024Review
- Plexin-B1 and Plexin-B2 play non-redundant roles in GABAergic synapse formation.Molecular and cellular neurosciences · 2024Article
- The microglial innate immune receptor TREM2 participates in fear memory formation through excessive prelimbic cortical synaptic pruning.Frontiers in immunology · 2024Article
- Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation.Nature communications · 2023Article
- Stress deficits in reward behaviour are associated with and replicated by dysregulated amygdala-nucleus accumbens pathway function in mice.Communications biology · 2023Article
- Spatially resolved gene regulatory and disease-related vulnerability map of the adult Macaque cortex.Nature communications · 2022Article
- Axon Guidance Molecules and Pain.Cells · 2022Review
- Neuronal circuitry for recognition memory of object and place in rodent models.Neuroscience and biobehavioral reviews · 2022Review
- SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance.Human molecular genetics · 2022Article
- Muscone Can Improve Spinal Cord Injury by Activating the Angiogenin/Plexin-B2 Axis.Molecular neurobiology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant fear is a cornerstone of several psychiatric disorders. Consequently, there is large interest in elucidation of signaling mechanisms that link extracellular cues to changes in neuronal function and structure in brain pathways that are important in the generation and maintenance of fear memory and its behavioral expression. Members of the Plexin-B family of receptors for class 4 semaphorins play important roles in developmental plasticity of neurons, and their expression persists in some areas of the adult nervous system. Here, we aimed to elucidate the role of Semaphorin 4C (Sema4C) and its cognate receptor, Plexin-B2, in the expression of contextual and cued fear memory, setting a mechanistic focus on structural plasticity and exploration of contributing signaling pathways. We observed that Plexin-B2 and Sema4C are expressed in forebrain areas related to fear memory, such as the anterior cingulate cortex, amygdala and the hippocampus, and their expression is regulated by aversive stimuli that induce fear memory. By generating forebrain-specific Plexin-B2 knockout mice and analyzing fear-related behaviors, we demonstrate that Sema4C-PlexinB2 signaling plays a crucial functional role in the recent and remote recall of fear memory. Detailed neuronal morphological analyses revealed that Sema4C-PlexinB2 signaling largely mediates fear-induced structural plasticity by enhancing dendritic ramifications and modulating synaptic density in the adult hippocampus. Analyses on signaling-related mutant mice showed that these functions are mediated by PlexinB2-dependent RhoA activation. These results deliver important insights into the mechanistic understanding of maladaptive plasticity in fear circuits and have implications for novel therapeutic strategies against fear-related disorders.
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