Figure 6

The effects of HINT1 on the responsiveness of NMDAR. (A) Spontaneous NMDAR-mediated currents in CA1 pyramidal neurons from WT and HINT1^-/- mice. The mean amplitudes of the spontaneous, NMDAR-mediated currents recorded in neurons from WT and HINT1^-/- mice in control conditions and when HINT1 was included in the solution of the recording pipette. The data are represented as the mean ± S.E.M. from WT (n = 12) and HINT1^-/- (n = 28) mice. * Significant difference p < 0.05. Representative whole-cell currents recorded from CA1 pyramidal neurons from WT and HINT1^-/- mice with the internal control solution and neurons recorded with HINT1 added to the internal solution. Higher amplitudes of the NMDAR-mediated slow inward currents were observed in HINT1^-/- mice relative to WT samples, which reverted in the presence of HINT1. The NMDAR antagonist D-AP5 (50 μM) abolished these currents. (B) The effect of mild stress induced by the forced swimming test on NMDAR activity in WT and HINT1^-/- mice. Thr286 CaMKII autophosphorylation and PKA-mediated Ser897 NR1 phosphorylation were measured in the controls and mice exposed to the test. Inset: PKA activity of cortical synaptosomes in WT and HINT1^-/- mice.