Fig. 1: Ccny knockout (KO) mice exhibit enhanced long-term potentiation (LTP) and moderate long-term depression (LTD).

a−i Electrophysiological characteristics of Ccny KO mice. a Neuronal intrinsic excitability is normal in Ccny KO mice. Data represent mean ± SEM of the number of action potentials triggered at each current step. The frequency of action potential firing was measured upon injecting a current step ranging from 0 to 330 pA in increments of 30 pA. ns, not significant compared to wild-type (WT) at each current step, Student’s unpaired t test. n = 15 and 16 cells from 4 WT and 3 KO mice, respectively. Representative action potentials recorded from WT and Ccny KO mice are shown. Scale bars, 20 mV, 100 ms. b–d The current-voltage relationship is not altered in Ccny KO mice. b Data represent mean ± SEM of the peak membrane potential measured at each current step. Membrane potential was measured upon injecting a current step ranging from 20 to −150 pA. ns, not significant compared to WT at each current step, Student’s unpaired t test. n = 15 and 16 cells from 4 WT and 3 KO mice, respectively. Representative voltage responses recorded from WT and Ccny KO mice are shown. Scale bars, 5 mV, 100 ms. Input resistance (c) and sag ratio (d) were calculated from the current-voltage relationship. Data represent mean ± SEM. ns, not significant, Student’s unpaired t test. e Paired-pulse ratio (PPR) remains unchanged in Ccny KO mice. Data represent mean ± SEM of PPR at each time interval. Two consecutive field excitatory postsynaptic potentials (fEPSPs) were evoked at Schaffer collateral-CA1 synapses with various time intervals (25, 50, 100, 200, and 400 ms). PPR was calculated by dividing the peak of the second fEPSP by that of the first one. ns, not significant, Student’s unpaired t test at each time interval. Representative fEPSP traces recorded from WT and Ccny KO mice are shown. Scale bars, 0.4 mV, 100 ms. f NMDA/AMPA ratio at hippocampal Schaffer collateral-CA1 synapses is normal in Ccny KO mice. Data represent mean ± SEM of NMDA/AMPA ratio. AMPAR-mediated currents recorded at −70 mV were measured at the peak amplitude, and NMDAR-mediated currents recorded at +40 mV were measured at 60 ms after stimulation. ns, not significant, Student’s unpaired t test. n = 9 and 11 cells from 4 WT and 3 KO mice, respectively. Representative excitatory postsynaptic currents (EPSCs) recorded at −70 mV (downward current) and +40 mV (upward current) from WT and Ccny KO mice. Scale bars, 100 pA, 100 ms. g Miniature EPSCs (mEPSCs) are not altered in hippocampal CA1 neurons from Ccny KO mice. (Upper) Representative recordings of AMPAR mEPSCs in hippocampal CA1 neurons from WT and Ccny KO mice. Scale bars, 40 pA, 5 s. (Lower) Both mEPSC amplitude (left) and frequency (right) are not altered by chronic Ccny KO. Cumulative distribution function plots of AMPAR mEPSC amplitude (left) and inter-event intervals (right). Insets, Data represent mean ± SEM. ns, not significant, Student’s unpaired t test. n = 8 and 9 cells from 5 animals each for WT and KO mice, respectively. h, i The input-output relationship is not altered at Schaffer collateral-CA1 synapses in Ccny KO mice. h fEPSPs were measured by stimulating the Schaffer collateral afferents with various stimulus intensity. (Upper) Representative fEPSP traces recorded from WT and Ccny KO mice with a series of increasing input stimulus ranging from 10 to 90 μA. Scale bars, 0.5 mV, 20 ms. (Lower) Data represent mean ± SEM of fEPSP slope at each stimulus intensity. ns, not significant, P = 0.669 (10 μA), P = 0.289 (20 μA), P = 0.430 (30 μA), P = 0.255 (40 μA), P = 0.403 (50 μA), P = 0.772 (60 μA), P = 0.935 (70 μA), P = 0.540 (80 μA), and P = 0.765 (90 μA) compared to WT at each stimulus intensity, Student’s unpaired t test. n = 11 and 12 slices from 6 WT and 5 KO mice, respectively. i Data represent mean ± SEM of the ratio of slope to volley. The ratio of fEPSP slope to the fiber volley amplitude at the stimulus strength that evokes 40% of the maximal fEPSP amplitude. ns, not significant, P = 0.662, Student’s unpaired t test. n = 11 and 12 slices from 6 WT and 5 KO mice, respectively. j, k LTP at Schaffer collateral-CA1 synapses is enhanced in Ccny KO mice. j High-frequency stimulation (HFS)-induced LTP is enhanced in Ccny KO mice. The magnitude of LTP was quantified as an increase in the fEPSP slope relative to the baseline. Representative fEPSP traces from WT and KO mice before (1) and after (2) LTP induction are shown. Scale bars, 0.2 mV and 10 ms. n = 8 and 8 slices from 5 WT and 6 KO mice, respectively. Data represent mean ± SEM of fEPSP slope. k Data represent mean ± SEM of averages of fEPSP slopes during the last 10 min (71−80 min) of the recordings in (j). *P < 0.05 as indicated, Student’s unpaired t test. l, m LTD at Schaffer collateral-CA1 synapses is reduced but still expressed in Ccny KO mice. l Ccny KO mice exhibit reduced hippocampal LTD induced by low-frequency stimulation (1 Hz, 900 pulses) at Schaffer collateral-CA1 synapses. The magnitude of LTD was quantified as a decrease in the fEPSP slope relative to the baseline. Data represent mean ± SEM. n = 7 and 7 slices from 7 WT and 6 KO mice, respectively. Representative fEPSP traces from WT and KO mice before (1) and after (2) LTD induction. Scale bars, 0.2 mV and 10 ms. m Data represent mean ± SEM of averages of fEPSP slopes during the last 10 min (66-75 min) of the recordings in (l). **P < 0.005 as indicated, Student’s unpaired t test. See also Supplementary Fig. S2.