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. 2011 Nov 16;31(46):16814–16825. doi: 10.1523/JNEUROSCI.3064-11.2011

Figure 9.

Figure 9.

Conditional knock-out of Hcn1. A, Representative currents recorded from an Hcn1-floxed vestibular hair cell negative for GFP and Cre-recombinase. B, Currents recorded from an Hcn1-floxed hair cell positive for GFP and Cre-recombinase after transfection with an Ad-Cre-GFP. Note the complete lack of Ih, which resembles currents from Hcn1-deficient mice (Fig. 5B). C, Ih recorded from a wild-type GFP-positive hair cell transfected with Ad-Cre-GFP. D, Representative currents from a mouse with hair cell deletion of Hcn1 through expression of Foxg1 Cre-recombinase. Note the complete lack of Ih, similar to B and to Hcn1-deficient tissue. E, Mean maximum conductance from 11 Hcn1-floxed cells, seven Hcn1-floxed cells infected with AdCre-GFP, four wild-type cells infected with AdCre-GFP, and nine Hcn1-floxed cells expressing Cre under the Foxg1 promoter. Asterisks mark statistically significant differences (p < 0.001) relative to Hcn1-floxed hair cells. F, Rotarod performance in six training trials of 20 conditional Hcn1 knock-out mice (white bars), six mice positive for Foxg1-Cre (striped bars), and 24 Hcn1-floxed mice without Cre expression (gray bars). Mice were ∼4–6 months old. Asterisks indicate statistically significant differences (*p < 0.05; **p < 0.005) between the Hcn1-floxed group and the Hcn1-floxed mice heterozygous for Foxg1-Cre. G, Performance of conditional Hcn1 knock-outs on accelerating testing tasks was also significantly worse in two of the four trials than the performance of mice with floxed alleles but no Cre-recombinase. H, I, Peak-to-peak amplitude measurements of vestibular-evoked potentials in three genotypes of mice. Amplitudes reported represent the difference in the first positive and first negative peak in the recorded waveform. Data were normalized to 0 dB SL, which represented the threshold response. H, We noted a significant decrease in amplitude at 6 dB SL (stimulus level) between the 14 Hcn1-floxed mice (white circles) and the four global Hcn1-deficient mice (gray triangles). I, There was also a significant decrease in amplitude at the 3 and 6 dB SL between 14 Hcn1-floxed mice (white circles) and the 10 Cre-positive Hcn1-floxed mice (gray squares).