Fig. 2
Mechanisms of TNF-mediated neuronal dysfunction in hyperinflammatory eCM. A Left: timeline for P. chabaudi infection and subsequent downstream analyses. Middle: presence of TNF protein in the hippocampus of IL-10−/− mice infected with P. chabaudi on day 7 p.i. (lysate collected from n = 4 mice). Right: diagrammatic representation of whole-cell patch-clamp recording in CA1 pyramidal neurons. B Representative traces of Nav1.6-mediated INa elicited by CA1 pyramidal neurons in response to the depicted voltage-clamp protocol in slices from the indicated experimental groups. C Comparison of current–voltage relationships of CA1 pyramidal neurons among the indicated experimental groups. D Comparison of V1/2 of activation of Nav1.6-mediated INa among the indicated experimental groups. E Comparison of V1/2 of inactivation of Nav1.6-mediated INa among the indicated experimental groups. F Representative traces of action potentials fired by CA1 neurons at the 180-pA injected current step. G Comparison of action potential discharge among the indicated experimental groups. H Comparison of action potential kinetics among the indicated experimental groups. Data are mean ± SEM (n = 6–11 neurons/group; recordings were performed in slices from at least N = 3 mice per group). Significance was assessed using a one-way ANOVA with post hoc Tukey’s multiple comparisons test. In (C, right, D, E, G, right, and H): ns, not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. In (G, left), * denotes current steps at which the number of action potentials fired by CA1 pyramidal neurons in slices from infected mice treated with vehicle is significantly greater (p is at least < 0.05) than the number of action potentials fired by CA1 neurons in other experimental groups