Figure 2.

CaN inhibition decreases neuronal excitability in CA1 hippocampal pyramidal neurons from naive animals. All measurements were performed with resting potential held at −65 mV. A, Current-clamp recording from pyramidal neuron dendrites showed that the mean IR from FK506-treated neurons was significantly reduced compared with control (**p < 0.01). Representative traces in response to 100 pA hyperpolarizing current injection are shown. The dendritic recording distances in control and FK506-treated neurons were 180 and 170 μm, respectively. IR from control and FK506-treated neurons in the presence of HCN channel blocker, ZD7288 (ZD), were increased and similar to each other, implying that the reduction in IR by FK506 was HCN channel dependent. B, TS of five 20 Hz α-function current injections in pyramidal neuron dendrites was also significantly reduced in FK506-treated slices compared with control (**p < 0.01). Representative traces show dendritic current-clamp recordings at 160 μm in both control and FK506-treated neurons. TS from control and FK506-treated neurons in the presence of ZD7288 were increased and similar to each other, implying that the reduction in TS by FK506 was HCN channel dependent. C, AP firing from dendritic depolarizing current injections (500 ms) showed decreased excitability in pyramidal neuron dendrites from FK506-treated neurons compared with control (*p < 0.05). Representative traces show dendritic backpropagating AP firing from dendritic depolarizing current injection (500 pA) at recording distances in control and FK506-treated neurons of 170 and 160 μm, respectively.