Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion

Neurons that lose part of their afferent input remodel their synaptic connections. While cellular and molecular mechanisms of denervation-induced changes in excitatory neurotransmission have been identified, little is known about the signaling pathways that control inhibition in denervated networks. In this study, we used mouse entorhino-hippocampal tissue cultures of both sexes to study the role of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha) in denervation-induced plasticity of inhibitory neurotransmission. In line with our previous findings in vitro, an entorhinal cortex lesion triggered a compensatory increase in the excitatory synaptic strength of partially denervated dentate granule cells. Inhibitory synaptic strength was not changed 3 days after the lesion. These functional changes were accompanied by a recruitment of microglia in the denervated hippocampus, and experiments in tissue cultures prepared from TNF-reporter mice [C57BL/6-Tg(TNFa-eGFP)] showed increased TNF alpha expression in the denervated zone. However, inhibitory neurotransmission was not affected by scavenging TNF alpha with a soluble TNF receptor. In turn, a decrease in inhibition, i.e., decreased frequencies of miniature inhibitory postsynaptic currents, was observed in denervated dentate granule cells of microglia-depleted tissue cultures. We conclude from these results that activated microglia maintain the inhibition of denervated dentate granule cells and that TNF alpha is not required for the maintenance of inhibition after denervation.

Automated summary

In this study, it was found that activated microglia maintain the inhibition of denervated dentate granule cells, while TNF alpha is not required for the maintenance of inhibition after denervation.