Figure 7.

Summary of the cascade of events underlying modulation of chloride homeostasis in the deafferented VN after UVN. In the adult, in physiological conditions or on the intact side of the VN (right side), the presence of KCC2 on the cells leads to a low [Cl⁻]_i concentration. When GABA activates GABA_AR, it then triggers a hyperpolarizing action through the influx of Cl⁻. After UVN (left side), microglia and astrocytes are strongly upregulated in the deafferented VN. We hypothesize that microglia, as well as nerve terminals, release BDNF, which in turn activates TrkB receptors and downregulates KCC2 expression. A lower concentration in KCC2 then decreases the chloride extrusion capacity of the cell; [Cl⁻]_i then accumulates and causes a collapse in the transmembrane chloride gradient. The anion flux being inverted, GABA_AR activation leads, in such conditions, to an efflux of Cl⁻, thus increasing the excitability of the cells. Interestingly, at the same time point (3 d after UVN), a peak of BrdU⁺ cells is observed on the lesioned side of the VN and is correlated with a peak of BDNF expression as well. This suggests that BDNF, released by both neurons and glia, could modulate cell proliferation, survival, and excitability.