Figure 6.

Loss of α9 nAChR activity perturbs a synapse specific CREB pathway. (A) Western blots of total cochlear lysate from α9 null and wild-type control mice at P7 and adult (2 months) ages, probed with antibodies against CREB pathway proteins as indicated. (B) Quantitative western blot analyses reveal a temporal interplay between N-Cadherin (data replotted from Fig. 4 for ease of comparison) and CREB Binding Protein (CBP) at P7 and adult ages in α9 null cochleae normalized to wild type expression levels. Note the downregulation of N-cadherin and upregulation of CBP at P7, followed by an increase of N-Cadherin expression and a reduction of CBP at the adult stage. Expression of presenilin, the γ-secretase responsible for final cleavage of the C-terminal tail of N-Cadherin and its release into the cytosol, does not significantly change across the ages examined. Total CREB expression increases in adult α9 null mice. Student’s t-test indicated significant changes with age for all proteins except presenilin. A two-way ANOVA analysis was run for the N-Cadherin and CBP data, given published functional links between these two proteins. This analysis demonstrated a highly significant interaction between expression of N-Cadherin and CBP across ages (p = 0.0005).