Sustained TNF signaling is required for the synaptic and anxiety-like behavioral response to acute stress

Acute stress triggers plasticity of forebrain synapses as well as behavioral changes. Here we reveal that Tumor Necrosis Factor alpha (TNF) is a required downstream mediator of the stress response in mice, necessary for stress-induced synaptic potentiation in the ventral hippocampus and for an increase in anxiety-like behaviour. Acute stress is sufficient to activate microglia, triggering the long-term release of TNF. Critically, on-going TNF signaling specifically in the ventral hippocampus is necessary to sustain both the stress-induced synaptic and behavioral changes, as these could be reversed hours after induction by antagonizing TNF signaling. This demonstrates that TNF maintains the synaptic and behavioral stress response in vivo, making TNF a potential novel therapeutic target for stress disorders.

Automated summary

Acute stress induces synaptic plasticity and behavioral changes in the brain. The study reveals that TNF is a crucial mediator in the stress response of mice, required for stress-induced synaptic potentiation and increased anxiety-like behavior. The activation of microglia leads to the long-term release of TNF, while sustained TNF signaling in the ventral hippocampus is necessary for maintaining the stress-induced changes.