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. 2024 Jul 16;15:5979. doi: 10.1038/s41467-024-50166-7

Fig. 4. Exogenous lactate restores spontaneous activity of orexinergic neurons from astrocytic MCT4 KD mice but not in orexinergic MCT2 KD mice.

Fig. 4

a Experimental design. Representative traces (b) and average firing rate (c, f) showing reduced firing in orexin neurons of aMCT4 KD (Controls and aMCT4 KD; n = 7 cells/4 mice; two-tailed Mann–Whitney test, ***p = 0.0006) and oMCT2 KD mice (Controls, n = 7 cells/4 mice; oMCT2 KD, n = 9 cells/4 mice; two-tailed Student t test, *p = 0.0131). d, g Membrane voltage (Vm) in aMCT4 KD (Controls, n = 7 cells/4 mice; aMCT4 KD, n = 6 cells/3 mice; two-tailed Student t test, *p = 0.0252) and oMCT2 KD mice (Control, n = 7 cells/4 mice and oMCT2 KD n = 9 cells/4mice; two-tailed Student t test **p = 0.0011). e, h Average input resistance (Rin) in aMCT4 KD (Control, n = 6 cells/3 mice; aMCT4 KD, n = 5 cells/3 mice; two-tailed Student t test, **p = 0.0082), and oMCT2 KD (Control, n = 7 cells/3 mice and oMCT2 KD n = 9 cells/4 mice; two-tailed Student t test, p = 0.28). i−k Lactate depolarization of an aMCT4 KD neuron was suppressed by 4-CIN. Representative trace (i) and average firing rate (j) ([Basal], n = 6 cells/4 mice; [Lactate], n = 6 cells/4 mice; [Lactate + 4-CIN], n = 5 cells/4 mice; Mixed-effects analysis followed by Tukey’s multiple comparison test, *p = 0.0107, *p = 0.0267). Same experiment as in (j) but in Control mice (k), ([Basal], n = 6 cells/3 mice; [Lactate], n = 6 cells/3 mice; [Lactate + 4-CIN], n = 4 cells/3 mice; Mixed-effects analysis followed by Tukey’s multiple comparison test, **p = 0.008, *p = 0.0176). No data points were excluded from the study. l, m Extracellular lactate had no effect on orexinergic activity from oMCT2 KD mice, while tolbutamide increased the activity. The bottom traces show an expanded timescale of the recording (l). Average firing (m) (n = 7 cells/5 mice; Friedman Test followed by Dunn’s multiple comparisons test, *p = 0.022, **p = 0.009). n Tolbutamide increased orexinergic activity from aMCT4 KD (n = 5 cells/3 mice; two-Tailed paired Student’s t test, **p = 0.0037) but had no effect in Control mice (n = 4 cells/3 mice; two-Tailed paired Student’s t test; p = 0.33). Pooled data are expressed as Mean values ± SEM. Source data are provided as a Source Data file.