Hippocampal synaptic plasticity in mice overexpressing an embryonic subunit of the NMDA receptor - PubMed (original) (raw)

Impaired synaptic plasticity in the hippocampi of NR2D transgenic mice. A, Sample traces of fEPSP of normal (black) and transgenic (red) mice recorded in the stratum radiatum of the CA1 region of the hippocampal slice at maximal intensity. Right, Input–output relationship of slices from normal (_n_= 9) and transgenic (n = 9) adult animals. Both parameters were similar in both animal groups. The curve was generated by plotting the amplitude of the presynaptic volley versus the amplitude of the fEPSP. B, Isolated NMDA receptor-mediated synaptic responses were recorded in a medium containing 10 μ

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DNQX, 50 μ

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picrotoxin, 100 μ

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saclofen, and 0 m

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Mg2+. Under these conditions, a paired pulse stimulation was required to elicit a slow fEPSP that is mediated by NMDA receptors [interstimulus interval (ISI) of_10_, 20, and 30 msec]. The traces are averages of six separate slices from two animals in each group. The fEPSP of transgenic mice was smaller in magnitude than the fEPSP of normal mice. Using a 10 msec ISI, the fEPSP average was 2.7 ± 0.3 mV in transgenic mice and 3.7 ± 0.2 mV in the controls. At 20 msec, the fEPSP average was 2.8 ± 0.4 mV in transgenic mice and 4.8 ± 0.3 mV in the controls. At 30 msec, the fEPSP average was 2.9 ± 0.3 mV in transgenic mice and 3.8 ± 0.4 mV in the controls. All of these differences were significant (p < 0.001, t_test). Before the addition of the blockers, the input–output relationship was found to be similar in both animal groups; the maximal amplitude of the fEPSP in normal medium at 10 msec ISI was 4.86 ± 0.48 mV and 4.90 ± 0.40 mV in transgenic mice. Calibration: 2 msec, 2 mV for top 2 traces; 6 msec, 2 mV for bottom 2 traces). C, In adult (2-month-old) line 9 transgenic mice, LTP evoked by a single 100 Hz tetanic stimulation for 1 sec amounted to a 18 ± 8% potentiation above basal levels (filled circles;n = 20, slices; n = 8, mice) compared with a 54 ± 9% in the control slices (open circles; n = 20, slices;n = 8, mice). Thirty minutes after the tetanic stimulation, a train of stimuli at 1 Hz was applied for 10 min, resulting in fEPSP values of 6.6 ± 8% in the controls and 3 ± 8% in the transgenic mice. The transgenic mice show no significant change in synaptic response. The insets are superimposed sample traces of normal (left) and transgenic (right) animals during the course of the LTP experiments: baseline, post-tetanic potentiation, and LTP.D, In juvenile (3-week-old) line 9 hippocampus, the magnitude of LTP 30 min after tetanus is similar to that of controls (67 ± 10% and 53 ± 9% in control and transgenic mice, respectively; n = 20, slices in each group;n = 7, mice in each group). A transient depotentiation was seen in the control mice with a less pronounced effect in the transgenic animals (−29 ± 11% and 22 ± 8% in control and transgenic mice, respectively). E, LTD in adult normal and transgenic mice. The depressing stimulus trains are_1, 2, and 5 Hz applied at_arrows_ as indicated (n = 7, slices in each group; n = 6, mice in each group).F, Long-term depression of fEPSPs in juvenile (3-week-old) line 9 transgenic mice is impaired compared with the wild-type controls. The depressing stimulus trains are_1_, 2, and 5 Hz applied at_arrows_ as indicated. (n = 7, slices in each group; n = 3, mice in each group).