Figure 7
Hyperexcitability of CA3b pyramidal neurons in mice lacking aminopeptidase P1. (a) Mean traces of APs (n = 12 for each genotype) recorded in the CA3b pyramidal neurons. Inset, enlarged traces showing the peak amplitudes and time course of AP spikes. (b) Bar graphs represent the amplitude of APs in CA3b neurons. t(22) = 3.386, **p = 0.003 by Student’s t-test. (c) First order derivatives (dV/dt) of the membrane potential during the action potential were calculated from WT (n = 12, blue traces) and Xpnpep1−/− (n = 12; orange traces) CA3b neurons and plotted as a function of membrane voltage. (d) Sample traces of voltage response to hyperpolarizing current injection (500 ms) in CA3b pyramidal neurons. (e) Bar graphs represent the input resistance of CA3b pyramidal neurons measured by the hyperpolarizing step shown in (d). t(22) = − 4.15, ***p < 0.001 by Student’s t-test. (f) Voltage responses shown in (d) were normalized to their maximum amplitude, and the initial portion of the responses is shown with an expanded time scale. (g) Increased membrane time constant in Xpnpep1−/− CA3b neurons. t(22) = − 4.10, ***p < 0.001 by Student’s t-test. (h) Sample traces of APs recorded in CA3 neurons in response to depolarizing current pulses (100–500 pA, 500 ms). (i) Averaged F–I curves in CA3 pyramidal neurons from WT (n = 12 from 3 animals) and Xpnpep1−/− (n = 12 from 3 animals) mice. n.s., not significant (p > 0.05); *p < 0.05; **p < 0.01 by Student’s t-test. (j) The slopes of the F–I relationship measured between 100 and 300 pA of input current were plotted against Rin of each cell. The dashed line represents the best fit for the linear relation between the F–I gain and Rin. (k) Sample traces of membrane currents measured from WT and Xpnpep1−/− CA3b neurons. Inset, Voltage steps elicited from a holding potential of − 70 mV in 20 mV increments from − 120 to − 20 mV. (l) Current–voltage (I–V) relationship for net membrane current at the end of the voltage step recorded from Xpnpep1+/+ (n = 13 cells from 3 animals) and Xpnpep1−/− (n = 13 cells from 3 animals) CA3b neurons. n.s., not significant (p > 0.05); *p < 0.05; **p < 0.01 by Student’s t-test.
