ArticleMolecular neurodegeneration2019
Differences in neurotropism and neurotoxicity among retrograde viral tracers.
Article in Molecular neurodegeneration, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
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- A circuit linking dentate gyrus and retrosplenial granular cortex regulates fracture healing in male mice.Nature communications · 2026Article
- Deep Cellular and Spatial Profiling of the Mouse Spinal Cord Reveals Sex-Specific Neuron Types and the Ascending Projection Neuron Repertoire.bioRxiv : the preprint server for biology · 2026Article
- Whole-Brain Neural Connectivity to Cholinergic Neurons in the Lower Thoracic Intermediolateral Column.CNS neuroscience & therapeutics · 2026Article
- Nps-Expressing Neurons Receive Extensive Input From Auditory Brainstem Nuclei.The Journal of comparative neurology · 2026Article
- Spatial organization and sex differences of paraventricular hypothalamic oxytocin neurons projecting to distinct brain regions.Brain structure & function · 2026Article
- Organization of mouse prefrontal cortex subnetwork revealed by spatial single-cell multi-omic analysis of SPIDER-Seq.National science review · 2026Article
- MSI2 in the dentate gyrus and ovary regulates the reproductive endocrine homeostasis of female mice.Communications biology · 2025Article
- Hippocampal neural circuit mechanisms in Alzheimer's disease revealed by viral-genetic circuit mapping.Neurobiology of disease · 2025Review
- Article
- NPS neurons receive extensive input from auditory brainstem nuclei.bioRxiv : the preprint server for biology · 2025Article
- Neural networks of the mouse visceromotor cortex.Nature · 2025Article
- Green-to-red spectral labeling: A novel polysynaptic retrograde tracing strategy in the marker footprint mouse model.Animal models and experimental medicine · 2025Article
- Distinct subnetworks of the mouse anterior thalamic nuclei.Nature communications · 2025Article
- ATLAS: a rationally designed anterograde transsynaptic tracer.Nature methods · 2025Article
- Development of Cre-dependent retrograde trans-multisynaptic tracer based on pseudorabies virus bartha strain.Molecular brain · 2025Article
- Layer-Specific Connectivity and Functional Interference of Chrna2+ Layer 5 Martinotti Cells in the Primary Motor Cortex.The European journal of neuroscience · 2025Article
- Metabolic reprogramming by pseudorabies virus: nucleotide metabolism as a central vulnerability for viral replication and pathogenesis.Frontiers in microbiology · 2025Article
- Anatomical mapping of whole-brain monosynaptic inputs to the orbitofrontal cortex.Frontiers in neural circuits · 2025Article
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeurotropic virus-based tracers have been extensively applied in mapping and manipulation of neural circuits. However, their neurotropic and neurotoxic properties remain to be fully characterized.
methodsThrough neural circuit tracing, we systematically compared the neurotropism discrepancy among different multi-trans-synaptic and mono-synaptic retrograde viral tracers including pseudorabies virus (PRV), rabies virus (RV), and the newly engineered retro adeno-associated virus (rAAV2-retro) tracers. The (single-cell) RNA sequencing analysis was utilized for seeking possible attribution to neurotropism discrepancy and comparing cell toxicity caused by viral infection between glycoprotein-deleted RV (RV-∆G) and rAAV2-retro. Viral toxicity induced microglia activation and neuronal protein change were evaluated by immunohistochemistry.
resultsMulti-trans-synaptic retrograde viral tracers, PRV and RV, exhibit differential neurotropism when they were used for central neural circuit tracing from popliteal lymph nodes. Mono-synaptic retrograde tracers, including RV-∆G and rAAV2-retro, displayed discrepant neurotropic property, when they were applied to trace the inputs of lateral hypothalamic area and medial preoptic nucleus. rAAV2-retro demonstrated preference in cerebral cortex, whereas RV-∆G prefers to label basal ganglia and hypothalamus. Remarkably, we detected a distinct preference for specific cortical layer of rAAV2-retro in layer 5 and RV-∆G in layer 6 when they were injected into dorsal lateral geniculate nucleus to label corticothalamic neurons in primary visual cortex. Complementation of TVA receptor gene in RV-resistant neurons enabled EnvA-pseudotyped RV infection, supporting receptors attribution to viral neurotropism. Furthermore, both RV-∆G and rAAV2-retro exerted neurotoxic influence at the injection sites and retrogradely labeled sites, while the changes were more profound for RV-∆G infection. Finally, we demonstrated a proof-of-concept strategy for more comprehensive high-order circuit tracing of a specific target nucleus by combining rAAV2-retro, RV, and rAAV tracers.
conclusionsDifferent multi-trans-synaptic and mono-synaptic retrograde viral tracers exhibited discrepant neurotropism within certain brain regions, even cortical layer preference. More neurotoxicity was observed under RV-∆G infection as compared with rAAV2-retro. By combining rAAV2-retro, RV, and rAAV tracers, high-order circuit tracing can be achieved. Our findings provide important reference for appropriate application of viral tracers to delineate the landscape and dissect the function of neural network.
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