Chandelier
Established Member (Voting Rights)
Published version (paywalled): https://www.cell.com/neuron/abstract/S0896-6273(25)00551-3
Preprint (open access): https://www.biorxiv.org/content/10.1101/2025.02.18.638874v1.full
• Reactive microglia prune astrocytic processes surrounding vasopressin neurons
• Astrocyte pruning leads to glutamate spillover, increasing vasopressin neuron activity
• Microglia-mediated increases in neuronal activity lead to salt-dependent hypertension
The structural plasticity of astrocytes is associated with numerous physiological and pathological conditions; however, the mechanism underlying this process remains unknown.
To examine the basis for structural astrocyte plasticity, we used the classic example of the loss of astrocytic processes that takes place in the rat hypothalamic magnocellular system during chronic high-salt intake.
We discovered that a high-salt diet triggers a local accumulation of reactive microglia around vasopressin-secreting neurons but not in other brain areas.
Microglia phagocytose astrocytic processes, reducing astrocytic coverage of vasopressin neurons. The pruning of astrocytic processes impairs synaptic glutamate clearance, enabling activation of extrasynaptic glutamate NMDA receptors and increasing the activity of vasopressin neurons.
Inhibiting microglia-mediated astrocyte pruning attenuates the increased neuronal activity and vasopressin-dependent hypertensive phenotype of rats fed a high-salt diet. Thus, microglia orchestrate neuron-glia interactions and regulate neuronal activity through astrocyte pruning.
Preprint (open access): https://www.biorxiv.org/content/10.1101/2025.02.18.638874v1.full
Highlights
• A high-salt diet induces accumulation of reactive microglia around vasopressin neurons• Reactive microglia prune astrocytic processes surrounding vasopressin neurons
• Astrocyte pruning leads to glutamate spillover, increasing vasopressin neuron activity
• Microglia-mediated increases in neuronal activity lead to salt-dependent hypertension
Summary
Neuron-glia interactions play a central role in regulating synaptic transmission and neuronal excitability.The structural plasticity of astrocytes is associated with numerous physiological and pathological conditions; however, the mechanism underlying this process remains unknown.
To examine the basis for structural astrocyte plasticity, we used the classic example of the loss of astrocytic processes that takes place in the rat hypothalamic magnocellular system during chronic high-salt intake.
We discovered that a high-salt diet triggers a local accumulation of reactive microglia around vasopressin-secreting neurons but not in other brain areas.
Microglia phagocytose astrocytic processes, reducing astrocytic coverage of vasopressin neurons. The pruning of astrocytic processes impairs synaptic glutamate clearance, enabling activation of extrasynaptic glutamate NMDA receptors and increasing the activity of vasopressin neurons.
Inhibiting microglia-mediated astrocyte pruning attenuates the increased neuronal activity and vasopressin-dependent hypertensive phenotype of rats fed a high-salt diet. Thus, microglia orchestrate neuron-glia interactions and regulate neuronal activity through astrocyte pruning.
Ning Gu1 ∙ Olena Makashova1 ∙ Celeste Laporte1 ∙ Chris Qilongyue Chen1 ∙ Banruo Li1 ∙ Pierre-Marie Chevillard1 ∙ Graham Lean1 ∙ Jieyi Yang1 ∙ Calvin Wong2 ∙ Jonathan Fan2 ∙ Behrang Sharif3 ∙ Susana Puche Saud1 ∙ Misha Hubacek1 ∙ Katrina Y. Choe4 ∙ Margaret M. McCarthy5 ∙ Arkady Khoutorsky2 ∙ Charles W. Bourque6 ∙ Masha Prager-Khoutorsky1,7