Fig. 6: Genetic ablation of the PB/KF^FoxP2neurons blocks hypercapnia-induced respiratory drive.

AAV-FLEX-DTA injections in PB of the FoxP2-Cre mice and wild-type littermates selectively ablated the FoxP2 neurons in the PBcl and the KF regions of the FoxP2-Cre mice. Photomicrographs (a, b) from a wild-type mouse (with no Cre expression, a WT-DTA) and a FoxP2-Cre mouse b injected with AAV-mCherry-Flex-DTA, immuno-labeled for FoxP2 (green) and mCherry (red), at three levels (rostal, middle, and caudal; a₁–b₃), with magnified merged panels of FoxP2 and mCherry for better view. The photomicrographs show that the spread of the AAV-DTA injection with mCherry labeling covered both KF and PB regions in (a, b). In the first group of mice a that lacked cre-recombinase, AAV-FLEX-DTA did not ablate the KF^FoxP2 and the PB^FoxP2 neurons (green); while in b where the virus injections were in the FoxP2-Cre mice, very few FoxP2 cells in the KF and the PBcl were spared (b PB + KF^FoxP2-DTA). However, both groups showed expression of mCherry in neurons in PBcl and PBel which lacked FoxP2. Scale in a₁–b₃ = 100 µm. KF Kölliker-Fuse PB subnucleus, PBel external lateral PB subnucleus, scp superior cerebellar peduncle, vsct ventral spinocerebellar tract. Genetic ablation of both PB^FoxP2 and KF^FoxP2 neurons significantly reduced the increases in V_T (d) and MV (e) but not RR (c) caused by CO₂ exposure (hypercapnia shown by a yellow rectangle). Values of RR, V_T, and MV are mean ± SEM (n = 8 WT-DTA; PB + KF^FoxP2-DTA = 5). Two-way ANOVA, with *P < 0.05; **P < 0.001, followed by Holms-Sidak method for multiple comparisons, for PB + KF^FoxP2-DTA compared to the WT-DTA. Source data are provided as a source data file.