Figure 4. Blockade of I_h Prolongs Ca²⁺ Signals Elicited by Perforant Path but Not Schaffer Collateral Stimulation.

Dendritic Ca²⁺ signals in proximal or distal CA1 dendrites in response to 100 Hz burst stimulation (10 stimuli) of SC or PP inputs, respectively, under control conditions (black) or in the presence of 10 μM ZD7288 (red). Ca²⁺ signals were measured with higher affinity Ca²⁺ dye, Fluo-4 (400 μM).

(A1) Effects of ZD7288 on proximal dendritic Ca²⁺ signals (top) and somatic voltage response (bottom) elicited by stimulation of SC synapses. (A2) Effects of ZD7288 on distal dendritic Ca²⁺ signals and somatic voltage response induced by burst stimulation of PP inputs. Distal but not proximal Fluo-4 Ca²⁺ signals are prolonged by ZD7288.

(B) Effects of ZD7288 on Ca²⁺ signal half-width duration in distal dendrites in response to PP stimulation or in proximal dendrites in response to SC stimulation. Grey symbols and lines show half-width durations for each individual experiment. Black symbols and lines show mean values. Values for distal dendrites in response to PP stimulation: Control: HW = 558.6 ± 118.11 ms; ZD7288: HW = 995 ± 245.53 ms; n = 10; p < 0.01, paired t test. Values for SR dendrites with SC stimulation: Control: HW = 150.67 ± 4.64 ms; ZD7288: HW = 144 ± 2.26 ms; n = 6, p = 0.14.

(C) Summary of effects of ZD7288 on HW and peak Ca²⁺ signals (ΔS/S₀) elicited by PP (Control: ΔS/S₀ = 146.3% ± 17.7%, ZD7288: ΔS/S₀ = 145.3% ± 14.1%; p = 0.92) and SC stimulation (Control ΔS/S₀ = 292.59% ± 29.8%, ZD7288 ΔS/S₀ = 226.36% ± 35.1%, p = 0.08).